Prevalence and molecular characterisation of multi-drug resistant ST11 hypervirulent Klebsiella pneumoniae in a teaching hospital

Prevalence and molecular characterisation of multi-drug resistant ST11 hypervirulent Klebsiella pneumoniae in a teaching hospital | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prevalence and molecular characterisation of multi-drug resistant ST11 hypervirulent Klebsiella pneumoniae in a teaching hospital Xue Li, Kai Ma, Xin Liu, Ping Cheng, Lailai Li, Yihui Chai, Mingle Cao, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5028260/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Jun, 2025 Read the published version in BMC Microbiology → Version 1 posted 10 You are reading this latest preprint version Abstract Background: Infections caused by carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HVKP) pose a critical challenge in clinical management due to limited treatment options and high mortality. Elucidating their virulence determinants and resistance mechanisms is essential for optimizing antimicrobial strategies and improving patient outcomes. Methods: We conducted a retrospective analysis of 102 carbapenem-resistant CRKP strains. Antimicrobial susceptibility testing was performed using the broth microdilution method, and resistance genotypes were characterized via PCR and Sanger sequencing. Virulence factors were identified through genomic sequencing and validated in a murine survival model (n=6 mice per strain). Conjugation assays were performed to assess the transferability of resistance and virulence genes, with recipient strain E. coli J53, and transfer events were confirmed by PCR. Results: CRKP strains were predominantly derived from sputum-, urine- and blood-specimens. Patients with CRKP infections predominantly had pulmonary infections. CRKP exhibited high resistance to other β-lactam antibiotics, mainly due to the presence of bla KPC-2 , high resistance to quinolones mediated by the carriage of aac (6''-Ib-cr) , QnrS and QnrB , and high resistance to aminoglycosides mediated by the carriage of rmtB , ant(3'')-I and armA . CR-HVKP is mainly composed of ST11. Aerobactin ( iucA, iutA ), Ent siderophore ( fepA, entB ), Salmochelin ( iroN ), Yersiniabactin ( ybtS ), Type 3 fimbriae ( mrkD ), Type I fimbriae ( fimH ), and Regulation ( p rmpA ) were detected in the CR-HVKP isolates. The CR-HVKP strains had a median lethal dose (LD 50) of 2 × 10 3 to 5 × 10 3 CFU in the mice, which was similar to that of the positive control NTUH-K2044. Conjugation assays revealed that the genes iucA, iutA, iroN, p rmpA , bla KPC-2 , bla NDM-1 , bla VIM , bla SHV-12 , bla TEM-1b , QnrA, QnrB, QnrS , and rmtB can be transferred to E. coli J53. Compared with those of the recipient E. coli J53, the MICs of meropenem, imipenem, levofloxacin and amikacin in the transconjugants increased by 4-128 times. Conclusions: These findings reveal that carbapenems in combination with aminoglycosides and quinolones may not be an effective option for the treatment of CRKP infections. Furthermore, the virulence and resistance genes may spread rapidly, which posing a public health risk and a significant threat to clinical care. Therefore, it is necessary to further strengthen hospital infection monitoring, prevention and control measures and to provide strict management and training on the rational use of antimicrobial agents in intensive care units. Klebsiella pneumoniae susceptibility clinical characteristics virulence factors resistance genes transconjugants Figures Figure 1 Figure 2 Background Klebsiella pneumoniae ( K. pneumoniae, KP) is a common cause of community-associated and nosocomial bacteraemia [1]. In immunocompromised individuals, such as those with diabetes or cancer, KP is an opportunistic pathogen that can cause a variety of diseases, including pneumonia, bacteremia, urinary tract infections, and meningitis. The subsequent spread of KP into the blood, which results in bacteremia, is a very serious side effect of KP pneumonia and UTIs [2]. KP can be divided into two groups, classical KP (cKP) and hypervirulent KP (HVKP), according to their pathogenicity. HVKP is distinguished from classical KP (cKP) by its enhanced pathogenicity, primarily driven by unique virulence factors such as capsular polysaccharides (e.g., K1, K2 serotypes), iron-uptake systems (aerobactin, yersiniabactin), and regulatory genes ( rmpA ). While cKP may possess basic virulence traits like fimbriae ( fimH ), HVKP uniquely harbors hypermucoviscosity-associated genes ( rmpA ) and specialized siderophores (e.g., iucA , iroN ), enabling invasive infections in immunocompetent hosts. The development and spread of HVKP has increased the range of individuals who are susceptible to infections, including those with adequate immune systems and good health [3]. The best characterized virulence factors were capsule, lipopolysaccharide (LPS), iron uptake (also known as siderophores), and fimbriae [3]. The string test has been used frequently to identify HVKP strains, and hypervirulence has been indicated by hypermucoviscosity [4]. Hypermucoviscosity is characterized as a positive string test by stretching a KP colony with a bacteriological loop on an agar plate, which manifests as a viscous filament greater than 5 mm in length [4], while not all hypervirulent strains exhibit the hypermucoviscous phenotype, and not all hypermucoviscous strains lead to an invasive syndrome [5]. The most common HVKP serotypes include K1, K2, K20, K54, and K57, with K1 and K2 being the most virulent, accounting for 70% of HVKP isolates [6]. Multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug resistant (PDR) isolates were classified as those that were resistant to at least one antibiotic in three or more classes, at least one antibiotic in all but two or fewer classes, and all drugs tested across all major antimicrobial classes. [7]. With the emergence of MDR, XDR and PDR-KP, choosing the appropriate antibiotic prescription to treat infections can be difficult for physicians given that patients often present with serious infections and complications [8]. As carbapenems have been the standard treatment approach for the systemic treatment of serious infections caused by gram-negative bacteria, carbapenem resistance presents new and difficult challenges in therapeutic decision-making, particularly because of the high frequency of co-resistance. An overview of the treatment options for selected pathogens and patterns of resistance was reported in previous literature [9]. Clinical isolates of metallo-beta-lactamase (MBL)-producing or KPC-producing K. pneumoniae are susceptible to quinolones and aminoglycosides and can be treated with quinolones or aminoglycosides in combination with meropenem. However, if the clinical strain is resistant to quinolones and aminoglycosides, tigecycline, colistin or fosfomycin is chosen in combination with meropenem [9]. Recent studies highlight the rising prevalence of quinolone (e.g., aac(6 ’ )-Ib-cr , qnrS ) and aminoglycoside (e.g., rmtB , armA ) resistance in carbapenemase-producing Enterobacterales. Evidence suggests that patients who are infected by carbapenem-resistant pathogens have an increased likelihood of morbidity and mortality compared with those infected by susceptible pathogens [10-12], which is likely due to the administration of antibiotics with suboptimal or no activity against these organisms [13]. Thus, recognizing the risk of carbapenem resistance, particularly in the most vulnerable patient populations [14, 15], and/or early detection of specific carbapenem resistance mechanisms [16] are critical to reduce the risk of mortality, length of hospitalization, and associated costs [12]. Enterobacterales pathogens resistant to carbapenem (CRE) have been placed in the highest priority category in the 2024 Global Priority Pathogens List published by the World Health Organization (i.e., critical) [17]. Identification and ongoing monitoring of CRE are needed to address this global epidemic. In this study, we carried out (1) the susceptibility of nosocomial KP strains to antimicrobial drugs such as β-lactams, carbapenems, quinolones, tetracyclines, aminoglycosides, polymyxins, and sulfonamides; (2) the resistance phenotypes of 102 CRKP strains and the clinical characteristics of patients with CRKP infections; (3) the virulence factors mediating the high virulence of CR-HVKP strains and the virulence factors mediating the high virulence of CR-HVKP strains; (4) the multilocus sequence typing and resistance genes mediating the resistance of CR-HVKP strains to carbapenems, aminoglycosides, quinolones, and sulfonamides; and (5) the susceptibility of CRKP and CR-HVKP strains to tigecycline, colistin, and fosfomycin to support clinicians in drug selection and regimen development for the treatment of nosocomial CRKP and CR-HVKP-induced infections. Materials and Methods Species identification and antimicrobial susceptibility Isolates were collected from The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, a tertiary-care university teaching hospital with 2629 beds serving diverse clinical departments. All 674 KP isolates were identified in the clinical laboratory from December 2020 to January 2022 using colony morphology, Gram stain, biochemical tests, and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (TECO-HYGI Mass Spectrometer EXS3000, China) in accordance with the manufacturer’s instructions. Antimicrobial susceptibility testing (AST) was performed using the Vitek 2 system (bioMérieux, Marcy-l’Étoile, France) for initial screening, with confirmatory broth microdilution for critical antibiotics (e.g., carbapenems, fosfomycin) following CLSI M100-S34 guidelines. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of imipenem (IPM), meropenem (MEM), ertapenem (ETP), ampicillin/Sulbactam (SAM), cefazolin (CZO3), cefotetan (CTT), ceftriaxone (CRO), piperacillin/tazobactam (TZP), ceftazidime (CAZ), cefepime (FEP), ampicillin (AMP), amoxicillin/clavulanic acid (AMC), ticarcillin (TIC), piperacillin (PIP), cefalotin (CFT), cefazolin (CZO), cefuroxime (CXM), aztreonam (ATM), cefoxitin (FOX), cefixime (CFM), cefotaxime (CTX), cefoperazone/sulbactam (CSL), nalidixic acid (NAL), ofloxacin (OFX), ciprofloxacin (CIP), levofloxacin (LVX), nitrofurantoin (NIT), tetracycline (TCY), compound trimethoprim (SXT), gentamicin (GEN), tobramycin (TOB), amikacin (AMK), and cefuroxime axetil. K-B silver diffusion was performed with minocycline. The production of extended-spectrum β-lactamase (ESBL) was tested in all the strains. Extended-spectrum β-lactamase (ESBL) production was detected using the combined disk synergy test (CDST) with cefotaxime/clavulanic acid and ceftazidime/clavulanic acid, per CLSI M100-S34 criteria, with cefotaxime (30 μg) and ceftazidime (30 μg) disks alone and in combination with clavulanic acid (10 μg). A ≥5 mm increase in the inhibition zone diameter with clavulanic acid was considered positive for ESBL production [4]. Escherichia coli ATCC 25922 and K. pneumoniae ATCC 700603 were used as controls and obtained from the American Type Culture Collection (ATCC). AST results were interpreted using CLSI M100-S34 breakpoints [18]. The MIC 50 and MIC 90 of each antibiotic were defined as the lowest concentration of the antibiotic required to inhibit 50 and 90% of isolates, respectively. The isolates were defined as CRKP if they were resistant to at least one of the carbapenem agents, including imipenem, ertapenem, and meropenem. A total of 102 nonrepetitive clinical CRKP isolates were used in further studies [18]. Clinical Data In this study, clinical data from 674 patients with Klebsiella pneumoniae (KP) infection were retrospectively reviewed, of whom 102 had isolates demonstrating carbapenem resistance (CRKP). Information on 102 patients with CRKP infection was statistically analysed. In addition to demographic information such as age, sex, and basic medical history, the survey also asked about hospitalization features such as sample source and department of separation, among others. Noninfected patients whose clinical samples were taken as part of the standard hospital laboratory practice were excluded. Virulence assay K. pneumoniae was isolated from patient samples and identified using accepted clinical microbiologic techniques (CLSI, 2024). The string test was carried out by touching a colony with a loop and tugging up after inoculation on TSB agar plates and overnight incubation at 37℃. The string test was determined to be positive when a viscous string over 5 mm in length was produced [19]. Twenty-three carbapenem-resistant CRKP isolates positive for the string test, a phenotypic marker of hypermucoviscosity, were selected from the study. Strains NTUH-K2044 and HS11286 were used as positive controls and negative controls, respectively. The best characterized virulence factors, Aerobactin ( iucA, iutA ), Ent siderophore ( fepA, entB ), Salmochelin ( iroB, iroN ), Yersiniabactin ( ybtS ), Type 3 fimbriae ( mrkD ), Type I fimbriae ( fimH ), Regulation ( p rmpA, p rmpA2, c rmpA ), and Capsular serotype-specific genes (K1, K2, K5, K20, K54, K57, K47 and K64), were detected by polymerase chain reaction (PCR) [20, 21]. Virulence genes were detected via PCR using primers listed in Supplementary Table S1. PCR products were sequenced using Sanger sequencing (Illumina NextSeq 500 platform), with sequence alignment and interpretation via BLAST on the NCBI database. Genomic sequences were analyzed using the Basic Local Alignment Search Tool (BLAST) suite (NCBI, USA) to identify virulence factors. Nucleotide and protein sequences were queried against the NCBI Nucleotide (nt) databases. BLASTp was employed for virulence factor annotation using the Virulence Factors of Pathogenic Bacteria database (VFDB). Mouse survival assay The mouse survival assay was performed as described previously [20] with a minor modification to define the inoculum volume and optimize animal welfare. Four KP isolates were used in the mouse survival assay: KP66974, KP62811, KP65640 and KP55182. Strains were selected for gene analysis if they were CR-HVKP (string test-positive + core virulence genes: rmpA, iucA, iroN ). KP strains NTUH-K2044 (phenotype pattern of ST23, K1, allS, peg-344, wzy-K1, entB, irp2, iroN, iucA, fimH, mrkD, c rmpA, p rmpA, p rmpA2, wzi , GenBank accession NC_012731) and HS11286 (phenotype pattern of ST11, K47, entB, irp2, fimH, mrkD, wzi , GenBank accession NC_016845) were used as positive controls and low-virulence controls, respectively. In brief, male specific pathogen-free (SPF) Kunming mice (18 to 20 g; n = 6 per group) were injected intraperitoneally with various titres of the 200 µL bacterial strains being assessed. The study endpoint, significant illness (in an extreme state), or death was observed in the animals for a maximum of seven days. For all six KP strains, a challenge inoculum of 2 × 10 3 to 5 × 10 3 CFU was initially used for all strains, with sequential challenges of 3 × 10 5 to 5 × 10 5 CFU and 3 × 10 7 to 6 × 10 7 CFU if all animals in the group survived a given challenge inoculum. The survival rate of the mice was recorded at 1, 2, 3, 4, 5, 6, and 7 days. All the surviving mice were euthanized under isoflurane anesthesia in order to alleviate the pain. K‒M survival curves were plotted using GraphPad Prism [20, 22]. Molecular Detection of Antibiotic Resistance Genes PCR was performed to detect common carbapenem resistance genes (carbapenemase, bla KPC and bla GES , metalloenzyme, bla NDM , bla VIM , bla IMP and bla SPM ,oxacillinase, bla OXA-48 ), ESBLs ( bla SHV , bla TEM , bla CTX-M1 , bla CTX-M2 , bla CTX-M8 , bla CTX-M9 ), plasmid-mediated quinolone resistance genes (5 quinolone resistance proteins, qnrA, qnrB, qnrC, qnrD and qnrS , one quinolone-modifying enzyme, aac(6')-Ib-cr , encoding quinolone efflux pump proteins, qep, oqxA and oqxB ), encoding AME genes ( aac(3')-II, aac(6')-Ib, aac(6')-II, ant(3'')-I, aph(3')-VI ), encoding 16S rRNA methyltransferases ( armA and rmtB ), conferring high-level aminoglycoside resistance, and sulfonamide determinants ( sul1 , sul2 ). The primer sequences and amplicon sizes are shown in Supplementary Table S2. Antimicrobial resistance (AMR) genes were screened in all 102 CRKP isolates using PCR. Using the NextSeq 500 sequencing platform, the positive PCR products were sequenced (Illumina, San Diego, CA, USA). BLAST was used to compare nucleotide sequences on the NCBI website (http://blast.ncbi.nlm.nih.gov/Blast.cgi). Conjugation assay A conjugation assay was carried out to investigate whether these virulence genes and resistance genes could be transferred. Donor isolates were selected based on their divergent virulence phenotypes in mouse survival assays: KP66974 (≤33.33% survival at 2 × 10³–5 × 10³ CFU) and KP65640 (100% survival at 2 × 10³–5 × 10³ CFU), to investigate whether transferable genetic elements underlie the acquisition of hypervirulence and resistance during conjugation. The E. coli J53 as recipient isolate. The donors and recipients were cultured in Luria–Bertani (LB) broth (37℃) to the logarithmic phase. The donors and recipients were mixed at a 2:1 ratio, centrifuged at 8,000 × g for 1 min, and resuspended in 20 mL of MgSO4 (10 mM). The resuspension was spread evenly on LB plates and incubated at 37℃ overnight. Subsequently, the serial dilutions were plated in media supplemented with the appropriate antibiotics (meropenem, 32 mg/L; levofloxacin, 8 mg/L; amikacin, 64 mg/L; and sodium azide, 100 mg/L) [23]. Transconjugants were selected on LB plates containing meropenem (32 mg/L), levofloxacin (8 mg/L), amikacin (64 mg/L), and sodium azide (100 mg/L) simultaneously, to ensure acquisition of all target resistance genes. Antimicrobial susceptibility, PCR, and DNA sequencing were used to confirm the presence of the iucA, iutA, iroN, p rmpA, bla KPC , bla NDM , bla VIM , bla TEM , bla GES , bla SHV , bla CTX-M2 , bla CTX-M9 , ant (3'')-I, OqxA, rmtB, aac (6')-Ib-cr, QnrA, QnrB, Qep, fepA, entB, ybtS, mrkD, fimH, and QnrS genes in the transconjugants. All primers used are listed in Supplementary Table S1 and Table S2. Multilocus Sequence Typing Multilocus sequence typing (MLST) was performed on all 23 CR-HVKP isolates to determine genetic relatedness. MLST of CR-HVKPwas performed according to previously described methods [24]. Seven conserved housekeeping genes ( gapA, infB, mdh, pgi, phoE, rpoB, and tonB ) were amplified, sequenced, and compared with those in the MLST databases (https://pubmlst.org/). The primer sequences and amplicon sizes are listed in Supplementary Table S3. Antimicrobial susceptibility of CRKP and CR- HVKP to tigecycline , colistin and fosfomycin The broth microdilution method (tigecycline and colistin) or agar dilution (fosfomycin) was used to determine the MICs for CR-HVKP and CRKP according to the standard protocols of the CLSI guidelines [18]. CLSI M100-S34 breakpoints were used for all antibiotics, except tigecycline, which followed EUCAST guidelines (≤2 µg/mL susceptible). Isolates with MICs ≥4 µg/mL for colistin, and ≥256 µg/mL for fosfomycin were considered resistant [18]. Statistical analysis TheStatistical Package for the Social Sciences (SPSS) version 22.0 was used to conduct a descriptive analysis utilizing mean, percentage, and frequency statistics (IBM Corporation, Armonk, NY, USA). Results Bacterial isolates K. pneumoniae resistance to carbapenems is defined as resistance to imipenem, meropenem or ertapenem. In total, 102 CRKP strains were identified from 674 (15.13%) KP strains collected from December 2020 to January 2022. The clinical characteristics of the 102 patients with CRKP infections are presented in Table 1. The mean±SD age of patients with CRKP infection was 75.89±16.17 (4-104 years), with an absolute male predominance of 76.47% (n=78). The CRKP strains were mainly derived from sputum specimens (68 strains, 66.67%), urine specimens (17 strains, 16.67%) and blood specimens (5 strains, 4.90%). Patients with CRKP infection were mainly located in intensive care units (ICUs, 55.88%), respiratory medicine units (PCCMs, 14.71%), and general surgery units (11.76%). The clinical diagnoses were mostly pulmonary infection, including community-acquired pneumonia (n=28, 27.45%), severe pneumonia (n=19, 18.63%), chronic obstructive pulmonary disease (n=15, 14.71%) and pneumonia (n=12, 11.76%). Table 1. Clinical characteristics of patients with CRKP infections Variable n(%) Demographics age (years), mean±SD 75.89±16.17 male 78 (76.47) Location at time of culture Intensive Care Medicine (ICU) 57 (55.88) Respiratory Medicine (PCCM) 15 (14.71) General Surgery 12 (11.76) Emergency Medicine Ward 7 (6.86) Gastroenterology 4 (3.92) Hematology Ward 3 (2.94) Orthopedic 3 (2.94) Pediatrics 1 (0.98) Infection source Sputum 68 (66.67) Urine 17 (16.67) Blood 5 (4.90) Bronchoalveolar lavage solution 4 (3.92) Pharyngeal swab 2 (1.96) Decubitus ulcers 2 (1.96) Secretions 2 (1.96) Catheter 1 (0.98) Peritoneal puncture fluid 1 (0.98) Comorbidity Community-acquired pneumonia 28 (27.45) Severe pneumonia 19 (18.63) Chronic obstructive pulmonary disease 15 (14.71) Pneumonia 12 (11.76) Septicemia 10 (9.80) Cerebral hemorrhage recovery 7 (6.86) Cerebral infarction sequelae 4 (3.92) Type 2 diabetes 3 (2.94) Gallbladder stones 2 (1.96) Dementia 1 (0.98) Epilepsy 1 (0.98) Antimicrobial susceptibility The antimicrobial susceptibility of CRKP to carbapenems, cephalosporins, quinolones, aminoglycosides, sulfonamides and tetracycline is shown in Table 2. The resistance rates of CRKP to imipenem, meropenem and ertapenem were 82.98%, 79.52% and 73.58%, respectively. The carbapenem-resistant isolates had MICs ranging from 0.25 to >16 mg/L, MIC 50 >16 mg/L, and MIC 90 >16 mg/L for imipenem; MICs ranging from 0.0625 to >32 mg/L, MIC 50 >32 mg/L, and MIC 90 >32 mg/L for meropenem; and MICs ranging from 0.12 to >8 mg/L, MIC 50 >8 mg/L, and MIC 90 >8 mg/L for ertapenem. Even the three compounds with the greatest inhibitory activity, MNO, CSL and AMK, inhibited CRKP by only 30.95%, 24.0% and 20.73%, respectively. In contrast, 85.57%-100% of CRKP strains were resistant to the other β-lactam antibiotics SAM (100%), CZO3 (100%), CTT (94.87%), CRO (95.6%), TZP (86.59%), CAZ (91.84%), FEP (85.57%), AMP (100%), AMC (91.23%), TIC (100%), PIP (100%), CFT (100%), CZO (100%), CXM (93.10%), ATM (95.74%), FOX (86.21%), CFM (100%), CTX (100%) and CXA (91.84%). The CRKP strains also exhibited high resistance rates to quinolones NAL (85.71%), OFX (87.50%), CIP (93.62%), LVX (91.84%), NIT (95%), TCY (100%), and SXT (88.89) and aminoglycosides GEN (95.74%) and TOB (95.74%). Resistance profile of 23 CR-HVKP is present in Table 3. Most of CR-HVKP strains are XDR, three of the CR-HVKP strains also produced ESBL. Overall, CRKP strains are highly resistant to cephalosporins, quinolones, aminoglycosides, tetracyclines, sulfonamides. Table 2. Antimicrobial susceptibility of CRKP to Carbapenems, cephalosporins, quinolones, aminoglycosides, sulfonamides, tetracycline Antibiotic subclasses R(%) I(%) S(%) MIC 50 (mg/L) MIC 90 (mg/L) MIC range (mg/L) β-Lactams IPM 82.98(78/94) 0(0/94) 17.02(16/94) >16 >16 0.25 to >16 MEM 79.52(66/83) 6.02(5/83) 14.46(12/83) >32 >32 0.0625 to >32 ETP 73.58(39/53) 1.89(1/53) 24.53(13/53) >8 >8 0.12 to >8 SAM 100(39/39) 0(0/39) 0(0/39) >32 >32 >32 CZO3 100(8/8) 0(0/8) 0(0/8) >64 >64 >64 CTT 94.87(37/39) 0(0/39) 5.13(2/39) >64 >64 4 to >64 CRO 95.6(87/91) 0(0/91) 4.4(4/91) >64 >64 0.25 to >64 TZP 86.59(71/82) 3.66(3/82) 9.76(8/82) >128 >128 4 to >128 CAZ 91.84(90/98) 0(0/98) 8.16(8/98) >64 >64 0.12 to >64 FEP 85.57(83/97) 7.22(7/97) 7.22(7/97) >32 >64 0.12 to >64 AMP 100(29/29) 0(0/29) 0(0/29) >32 >32 16 to >32 AMC 91.23(52/57) 0(0/57) 8.77(5/57) >32 >32 2 to >32 TIC 100(7/7) 0(0/7) 0(0/7) >32 >32 >32 PIP 100(8/8) 0(0/8) 0(0/8) >32 >32 >32 CFT 100(7/7) 0(0/7) 0(0/7) >16 >16 >16 CZO 100(33/33) 0(0/33) 0(0/33) >64 >64 4 to >64 CXM 93.10(54/58) 0(0/58) 6.90(4/58) >64 >64 1 to >64 ATM 95.74(45/47) 0(0/47) 4.26(2/47) >64 >64 2 to >64 FOX 86.21(50/58) 0(0/58) 13.79(8/58) >64 >64 4 to >64 CFM 100(8/8) 0(0/8) 0(0/8) 2 2 2 CTX 100(7/7) 0(0/7) 0(0/7) 2 2 2 CSL 76.00(57/75) 0(0/75) 24.00(18/75) >64 >64 8 to >64 CXA 91.84(45/49) 0(0/49) 8.16(4/49) >64 >64 1 to >64 Quinolones NAL 85.71(6/7) 0(0/7) 14.29(1/7) 32 32 16 to 32 OFX 87.50(7/8) 0(0/8) 12.50(1/8) 4 4 2 to 4 CIP 93.62(44/47) 0(0/47) 6.38(3/47) 4 4 0.25 to 4 LVX 91.84(90/98) 2.04(2/98) 6.12(6/98) 8 8 0.12 to 8 NIT 95.00(19/20) 5.00(1/20) 0(0/20) >512 >512 64 to >512 Tetracyclines TCY 100(8/8) 0(0/8) 0(0/8) 8 8 8 MNO ND30 17.86(15/84) 51.19(43/84) 30.95(26/84) / / / Tigecycline 1.27 (1/79) 2.53 (2/79) 96.20 (76/79) 0.5 2 0.25 to 16 Sulfonamides SXT 88.89(80/90) 0(0/90) 11.11(10/90) >320 >320 20 to >320 Aminoglycosides GEN 95.74(45/47) 0(0/47) 4.26(2/47) >16 >16 1 to >16 TOB 95.74(45/47) 0(0/47) 4.26(2/47) >16 >16 1 to >16 AMK 79.27(65/82) 0(0/82) 20.73(17/82) >64 >64 2 to >64 Polymyxin Colistin 1.27 (1/79) 98.73 (78/79) 0 (0/79) 1 2 0.5 to 16 Polyphosphate Fosfomycin 87.34 (69/79) 11.39 (9/79) 1.27 (1/79) 256 >512 64 to >512 R, resistant; I, intermediate; S, susceptible; IPM, Imipenem; MEM, Meropenem; ETP, Ertapenem; SAM, Ampicillin/Sulbactam; CZO3, Cefazolin (other); CTT, Cefotetan; CRO, Ceftriaxone; TZP, Piperacillin/tazobactam; CAZ, ceftazidime ; FEP, cefepime; AMP, Ampicillin; AMC, Amoxicillin/Clavulanic Acid; TIC, Ticarcillin; PIP, Piperacillin; CFT, Cefalotin; CZO, Cefazolin; CXM, Cefuroxime; ATM, Aztreonam; FOX, Cefoxitin; CFM, Cefixime; CTX, Cefotaxime; CSL, Cefoperazone/Sulbactam; NAL, Nalidixic acid; OFX, Ofloxacin; CIP, Ciprofloxacin; LVX, Levofloxacin; NIT, Nitrofurantoin; TCY, Tetracycline; MNO, Minocycline; Tigecycline, susceptibility ≤ 2 mg/L, intermediates =4 mg/L, resistant ≥ 8 mg/L; SXT, Compound trimethoprim; GEN, Gentamicin; TOB, Tobramycin; AMK, Amikacin; CXA, Cefuroxime Axetil. Colistin, intermediates ≤2 mg/L, resistant ≥4 mg/L; Fosfomycin, susceptibility≤ 64 mg/L, intermediates =128 mg/L, resistant ≥ 256 mg/L. Virulence assay As shown in Table 4, twenty-three (22.55%) of the 102 CRKP isolates were positive for both the string test and gene markers. The occurrence of HVKP gene markers was as follows: ybtS (100%, n =23), mrkD (100%, n =23), fimH (100%, n =23), iucA (95.65%, n =22), entB (95.65%, n =22), iutA (91.30%, n =21), fepA (91.30%, n =21), iroN (91.30%, n =21), and p rmpA (8.90%, n =2). The gene markers iroB and p rmpA2 were missing in all the isolates. In 86.96% (n=20) of the CR-HVKP strains, virulence genes ( iucA, iutA, fepA, entB, iroN, ybtS, mrkD , and fimH ) coexisted. In 8.90% (n=2) of the CR-HVKP strains, virulence genes ( iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH , and p rmpA ) coexisted. However, the virulence genes iucA, ybtS, mrkD , and fimH , as well as entB, ybtS, mrkD , and fimH , were present in only 4.35% (n=1) of the bacteria. HVKP was defined by string test positivity and detection of ≥2 virulence genes ( iucA, rmpA, iroN ). Capsule K1 was detected in 43.48% (n=10) of the CR-HVKP strains, whereas other serotypes not detected. The mean±SD age of patients with CR-HVKP infection was 75.89±16.17 years (64-104 years). CR-hvKP was associated with ICU admission (Fisher’s exact test, p=0.012) and bacteremia (OR=3.2, 95% CI:1.4–7.1). CR-HVKP strains are mainly derived from sputum and urine. Table 3. Resistance profile of 23 highly virulent k.pneumoniae. No. Isolates MIC of antimicrobials ESBL Resistance profile Degree of resistance Mer (mg/L) IMP (mg/L) 1 65821 >32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, CZO, ATM, CIP, LVX, SXT, GEN, TOB, AMK, CSL XDR 2 61977 >32 0.25 Pos MER, SAM, CTT, CRO, TZP, CAZ, CXM, LVX, SXT, GEN, TOB, CXA MDR 3 62811 2 16 Neg MER, IMP, CRO, TZP, CAZ, FEP, AMC, CXM, FOX, CSL, ETP, LVX, SXT, TOB, AMK, CXA XDR 4 61940 >32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CZO, ATM, CIP, LVX, NIT, SXT, GEN, TOB, AMK XDR 5 54559 32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMC, CXM, FOX, CSL, ETP, LVX, SXT, GEN, TOB, AMK, CXA XDR 6 55822 32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CZO, ATM, CSL, CIP, LVX, NIT, SXT, GEN, TOB XDR 7 58123 2 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CZO, ATM, CSL, CIP, LVX, SXT, GEN, TOB, AMK XDR 8 66974 >32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, CZO, ATM, CSL, CIP, LVX, SXT, GEN, TOB, AMK XDR 9 65852 >32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CZO, ATM, CIP, LVX, NIT, SXT, GEN, TOB, AMK XDR 10 61921 >32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CZO, ATM, CIP, LVX, NIT, SXT, GEN, TOB, AMK XDR 11 57802 >32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMC, CXM, FOX, CSL, ETP, LVX, SXT, GEN, TOB, AMK, CXA XDR 12 67835 8 2 Neg MER, CRO, TZP, CAZ, FEP, TIC, PIP, CXM, CZO, ATM, CFM, CTX, NAL, OFX, CIP, LVX, TCY, MNO, NIT, SXT, GEN, TOB, CSL XDR 13 65640 2 8 Neg MER, IMP, CRO, TZP, CAZ, FEP, AMC, CXM, FOX, ETP, LVX, MNO, SXT, TOB, AMK, CXA,CSL XDR 14 62080 0.0625 4 Pos MER, IMP, SAM, CRO, AMP, CZO, NIT, LVX, SXT, CXA MDR 15 65977 >32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CZO, ATM, CIP, LVX, NIT, MNO, SXT, GEN, TOB, AMK, CSL XDR 16 59572 >32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, ATM, CSL, CIP, LVX, NIT, SXT, GEN, TOB, AMK XDR 17 57773 >32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, ATM, CSL, CIP, LVX, NIT, SXT, GEN, TOB, AMK XDR 18 60485 >32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CXM, FOX, CSL, ETP, LVX, NIT, SXT, GEN, TOB, AMK, CXA XDR 19 67859 >32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CZO, ATM, CIP, LVX, NIT, SXT, GEN, TOB XDR 20 66798 32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMC, CXM, FOX, CSL, ETP, LVX, SXT, GEN, TOB, AMK, CXA XDR 21 64415 >32 16 Neg MER, IMP, SAM, CTT, CRO, CAZ, FEP, CZO, ATM, CIP, LVX, SXT, GEN, TOB, AMK, CSL XDR 22 59579 >32 16 Neg MER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMC, CXM, FOX, CSL, ETP, LVX, SXT, GEN, TOB, AMK, CXA XDR 23 55182 0.0625 4 Pos MER, IMP, CRO, CXM, ETP, LVX, SXT, CXA MDR MEM, Meropenem; IMP, Imipenem; ETP, Ertapenem; ESBL, Extended spectrum β-lactamase; SAM, Ampicillin/Sulbactam; CTT, Cefotetan; CRO, Ceftriaxone; TZP, Piperacillin/tazobactam; CAZ, ceftazidime ; FEP, cefepime; AMP, Ampicillin; AMC, Amoxicillin/Clavulanic Acid; TIC, Ticarcillin; PIP, Piperacillin; CZO, Cefazolin; CXM, Cefuroxime; ATM, Aztreonam; FOX, Cefoxitin; CFM, Cefixime; CTX, Cefotaxime; CSL, Cefoperazone/Sulbactam; NAL, Nalidixic acid; OFX, Ofloxacin; CIP, Ciprofloxacin; LVX, Levofloxacin; NIT, Nitrofurantoin; TCY, Tetracycline; MNO, Minocycline; SXT, Compound trimethoprim; GEN, Gentamicin; TOB, Tobramycin; AMK, Amikacin; CXA, Cefuroxime Axetil; .Neg Negative, Pos Positive, ND Not detected. Table 4. Virulence characteristics of 23 highly virulent Klebsiella pneumoniae No. Isolates Age (years) HD Infection source String Test Virulence genes Capsule ST 1 65821 89 EMW Blood Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH ND ST11 2 61977 75 EMW Urine Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH K1 ST11 3 62811 83 GA Urine Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH, p rmpA K1 ST11 4 61940 81 GS Secretions Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH ND ST11 5 54559 79 GS Sputum Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH K1 ST11 6 55822 82 GS Sputum Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH K1 ST11 7 58123 84 GS Sputum Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH ND ST11 8 66974 90 ICU Sputum Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH, p rmpA K1 ST11 9 65852 104 ICU Sputum Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH ND ST11 10 61921 76 ICU Sputum Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH K1 ST11 11 57802 85 ICU Sputum Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH K1 ST11 12 67835 79 ICU Sputum Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH K1 ST11 13 65640 79 ICU Sputum Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH K1 ST11 14 62080 94 ICU Sputum Pos iucA, ybtS, mrkD, fimH ND ST11 15 65977 85 ICU Urine Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH ND ST11 16 59572 64 ICU Urine Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH ND ST11 17 57773 81 ICU Urine Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH ND ST11 18 60485 83 ICU Urine Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH ND ST690 19 67859 85 ICU Urine Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH K1 ST11 20 66798 86 ICU Urine Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH ND ST11 21 64415 91 PCCM Sputum Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH ND ST11 22 59579 75 PCCM Sputum Pos iucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH ND ST11 23 55182 86 PCCM Sputum Pos entB, ybtS, mrkD, fimH ND ST1108 HD, Hospital Department; AR, antimicrobial resistance; PCCM, Respiratory Medicine; EMW, Emergency Medicine Ward; GS, General Surgery; GA, Gastroenterology; The related genes iucA, iutA and iroN are typically plasmid-encoded, which associated with Iron uptake; The r mpA gene-encoded HVKP gene is hypermucoviscous. The fimH and mrkD mediate adhesion by encoding KP type 1 and type 3 fimbriae, and mrkD may promote the development of biofilms. Neg Negative, Pos Positive, ND Not detected. Mouse survival assay To evaluate the virulence of CR-HVKP strains, six specific pathogen-free (SPF) Kunming mice per group were intraperitoneally injected with 200 µL of bacterial suspensions at three gradient titres: 2×10³-5×10³ CFU, 3×10 5 -5×10⁵ CFU, and 3×10⁷-6×10⁷ CFU, with survival rates monitored over seven days (Figure 1). At the lowest challenge dose (2×10³-5×10³ CFU), the hypervirulent control strain NTUH-K2044 induced 0% survival, while test strains showed varying resistance: KP66974, KP62811, and KP65640 yielded 33.33% (4/12 mice across two replicates), 50.00% (6/12 mice), and 83.33% (10/12 mice) survival, respectively. Increasing the inoculum to 3×10⁵-5×10⁵ CFU led to 100% mortality in NTUH-K2044-challenged mice, whereas KP66974 caused complete mortality (0% survival), KP62811 showed 16.67% survival, and KP65640 maintained 50% survival. In contrast, the low-virulence strains KP55182 and HS11286, serving as negative controls, exhibited 100% survival across all tested concentrations (2×10³–6×10⁷ CFU), confirming their avirulent phenotype and validating the model’s sensitivity to hypervirulent traits. These results demonstrate dose-dependent pathogenicity of CR-HVKP strains relative to control counterparts, with KP65640 showing the lowest virulence and NTUH-K2044 establishing a benchmark for hypervirulent lethality in this model. Genotypic prevalence and multilocus sequence typing The MLST and PCR amplification results of the carbapenem-ESBL-quinolones-aminoglycosides-sulfonamides-resistance genes of 23 CR-HVKP strains are presented in Table 4 and Figure 2. MLST revealed an overwhelming prevalence of ST11 (91.30%, 21/23) among the CR-HVKP strains, followed by ST690 (4.35%, 1/23) and ST1108 (4.35%, 1/23). Eighteen CR-HVKP strains were resistant to meropenem (17 strains had MICs ≥ 32 mg/L), three strains had intermediate MICs, and two strains were susceptible. Twenty-one CR-HVKP strains were resistant to imipenem (18 strains had an MIC =16 mg/L), one strain was an intermediate strain, and one strain was susceptible. The carbapenem-producing CR-HVKP strains was as follows: bla KPC-2 (91.30%, n = 21/23), bla VIM (86.96%, n = 20/23), bla GES (34.78%, n = 8/23) and bla NDM-1 (8.70%, n = 2/23). The bla IMP , bla SPM and bla OXA-4 8 were not detected in any of the isolates. Three CR-HVKP strains tested phenotypically positive for ESBL (CDST), while genotypic analysis detected ESBL genes ( bla CTX-M-9 , -2 , SHV-12 ) in 22/23 isolates. TEM-1b, a narrow-spectrum β-lactamase, was present in all strains but does not confer ESBL phenotype. Twenty-two strains of CR-HVKP are resistant to aminoglycosides. The distribution of aminoglycoside target genes among CR-HVKP strains was as follows: aac (6')-Ib-cr (100%, n = 23/23), rmtB (95.65%, n= 22/23), ant(3'')-I (86.96%, n=20/23), armA (65.22%, n= 15/23), aac(6')-II (21.74%, n = 5/23), and aac(3')-II (13.04%, n = 3/23). The aph(3')-VI were not detected in any of the isolates. All the CR-HVKP strains were resistant to quinolone. The distribution of quinolone target genes among CR-HVKP strains was as follows: aac (6')-Ib-cr (100%, n = 23/23), QnrS (86.96%, n= 20/23), OqxA (86.21%, n=19/23), QnrB (60.87%, n = 14/23), QnrD (43.48%, n= 10/23), Qep (30.43%, n= 7/23), QnrA (17.39%, n = 4/23), QnrC (8.70%, n=2/23) and OqxB (8.70%, n= 2/23). All the CR-HVKP strains were resistant to sulfonamide. The distribution of sulfonamide target genes among CR-HVKP strains was as follows: sul2 (100%, n = 23/23) and sul1 (73.91%, n = 17/23). Conjugation Assay The iucA, iutA, iroN, p rmpA , bla KPC-2 , bla NDM-1 , bla VIM , bla SHV-12 , bla TEM-1b , QnrA, QnrB, QnrS , and rmtB genes were successfully transferred from KP66974 to E. coli J53, and the conjugative transfer frequencies ranged from 1.3×10 -11 to 2.6×10 -5 . The genes fepA, entB, ybtS, mrkD, fimH, bla CTX-M2 , bla CTX-M9 , aac (6')-Ib-cr, and ant(3'')-I were not transferred to E. coli J53. Compared with those of the recipient E. coli J53, the MICs of meropenem, imipenem, levofloxacin, and amikacin increased 64-fold (from 0.5 to 32 mg/L), >16-fold (from <1 to 16 mg/L), 128-fold (from <0.0625 to 8 mg/L), and 64-fold (from <1 to 64 mg/L), respectively. The genes iucA, iutA, iroN, bla KPC-2 , bla GES , bla VIM , bla SHV-12 , bla TEM-1b , rmtB, QnrB, QnrD and QnrS were successfully transferred from KP65640 to E. coli J53, and conjugative transfer frequencies ranged from 4.2 ×10 -12 to 3.8×10 -4 . Compared with those of the recipient E. coli J53, the MICs of meropenem, imipenem, levofloxacin and amikacin in the transconjugants increased by 4-128 times (Table 5). Table 5 Transferability of virulence genes and resistance genes Organism name KP66974 E.coli J53 Transconjugants KP65640 E.coli J53 Transconjugants Meropenem, MIC (mg/L) >32 0.5 >32 2 0.5 2 Imipenem, MIC (mg/L) 16 ＜1 16 8 ＜1 8 Levofloxacin, MIC (mg/L) 8 0.0625 8 8 0.0625 8 Amikacin, MIC (mg/L) >64 ＜1 >64 >64 ＜1 >64 Gene markers iucA, iutA, iroN, prmpA, bla KPC-2 , bla NDM-1 , bla VIM , bla SHV-12 , bla TEM-1b , rmtB, QnrA, QnrB, QnrS Pos Neg Pos Conjugative transfer frequencies 1.3☓10 -11 to 2.6☓10 -5 Gene markers fepA, entB, ybtS, mrkD, fimH, bla CTX-M2 , bla CTX-M9 , aac (6')-Ib-cr, ant(3'')-I, OqxA Pos Neg Neg Gene markers iucA, iutA, iroN, bla KPC-2 , bla GES , bla VIM , bla SHV-12 , bla TEM-1b , rmtB, QnrB, QnrD, QnrS Pos Neg Pos Conjugative transfer frequencies 4.2 ☓10 -12 to 3.8☓10 -4 Gene markers fepA, entB, ybtS, mrkD, fimH, bla CTX-M2 , bla CTX-M9 , aac (6')-Ib-cr, ant(3'')-I, OqxA, Qep Pos Neg Neg Antimicrobial susceptibility of CRKP and CR-HVKP to tigecycline, colistin and fosfomycin The antimicrobial susceptibilities of CRKP and CR-HVKP to tigecycline, colistin and fosfomycin are presented in Table 6. The susceptibility rates of CRKP to tigecycline, colistin and fosfomycin were 96.20%, 0% and 1.27%, respectively, with MICs ranging from 0.25 to 16 mg/L, MIC 50 =0.5 mg/L, and MIC 90 =2 mg/L for tigecycline; MICs ranging from 0.5 to 16 mg/L, MIC 50 =1 mg/L, and MIC 90 =2 mg/L for colistin; and MICs ranging from 64 to >512 mg/L, MIC 50 =256 mg/L, and MIC 90 >512 mg/L for fosfomycin. The susceptibility rates of CR-HVKP to tigecycline, colistin and fosfomycin were 100%, 0 and 0, respectively, with MICs ranging from 0.25 to 2 mg/L, MIC 50 =0.5 mg/L, and MIC 90 =2 mg/L for tigecycline; MICs ranging from 0.5 to 2 mg/L, MIC 50 =1 mg/L, and MIC 90 =2 mg/L for colistin; and MICs ranging from 128 to >512 mg/L, MIC 50 =256 mg/L, and MIC 90 =512 mg/L for fosfomycin. Table 6. Antimicrobial susceptibility of CRKP to tigecycline, colistin and fosfomycin Isolates Antibiotic R (%) I (%) S (%) MIC 50 (mg/L) MIC 90 (mg/L) MIC range (mg/L) CRKP (n=79) Tigecycline 1.27 (1/79) 2.53 (2/79) 96.20 (76/79) 0.5 2 0.25 to 16 Colistin 1.27 (1/79) 98.73 (78/79) 0 (0/79) 1 2 0.5 to 16 Fosfomycin 87.34 (69/79) 11.39 (9/79) 1.27 (1/79) 256 >512 64 to >512 Hv-CRKP (n=23) Tigecycline 0 (0/23) 0 (0/23) 100 (23/23) 0.5 2 0.25 to 2 Colistin 0 (0/23) 100 (23/23) 0 (0/23) 1 2 0.5 to 2 Fosfomycin 91.30 (21/23) 8.70 (2/23) 0 (0/23) 256 512 128 to >512 Tigecycline, susceptibility ≤ 2 mg/L, intermediates =4 mg/L, resistant ≥ 8 mg/L; Colistin, intermediates ≤2 mg/L, resistant ≥4 mg/L; Fosfomycin, susceptibility≤ 64 mg/L, intermediates =128 mg/L, resistant ≥ 256 mg/L. Discussion Infections caused by CRKP isolates are a major threat to public health. Such infections increase the mortality rate of critically ill and debilitated patients hospitalized in intensive care units (ICUs) and add to the significant economic burden. CRE has been recognized and continuously monitored in different countries around the globe in response to this global epidemic. The prevalence of CRKP in Europe ranges from 0% to 69.7%, with a high prevalence in Bulgaria (56.8%), Romania (52.8%), and Greece (69.7%) in 2023 [25]. The resistance rate of KP to carbapenems in China ranged from 2.9% in 2005 to 26.0% in 2023. In particular, the resistance rate has remained above 24.0% for the past seven years [26]. KP strains collected from 2020 to 2022 were found to be 15.13% resistant to meropenem or imipenem in this study, which is lower than the average resistance of CRKP strains in China. The molecular epidemiology of CRKP isolates is important because it can be used to identify potential treatment options. The clinical characteristics of the 102 patients with CRKP infections included in this study are presented in Table 1. These findings imply that older males are more likely to have CRKP. The findings were similar to those of a previous study [27]. Women generally have stronger immune responses to both self-antigens and foreign antigens than men, which leads to gender-based differences in autoimmune diseases and infectious diseases. In both animals and humans, on the whole, men are usually more susceptible to bacterial infections than women [28]. CRKP strains were predominantly detected in sputum specimens, urine specimens and blood specimens. Patients with CRKP infections were mainly concentrated in intensive care units, respiratory medicine units and general surgery units. The clinical diagnoses were mostly lung infections, including community-acquired pneumonia, severe pneumonia, chronic obstructive pulmonary disease and pneumonia. According to a previous study, 50% of nosocomial KP bacteremia cases were caused by lung-related primary infections [29]. KP bacteremia frequently results in death. KP bacteraemia is associated with mortality rates ranging from 27.4 to 37% [30-32]. CR-HVKP infection was statistically associated with increased ICU admission (p = 0.012) and mortality (p = 0.028, Table 1), though these observations are limited by the single-center design. Prospective studies are needed to validate these associations across populations [31-33]. The results suggest that the focus should be on susceptibility to carbapenems in patients with pulmonary infections in intensive care units and respiratory medicine departments, especially in patients with multiple risk factors for CRKP infections and comorbidities, including the use of central venous catheters, mechanical ventilation, tracheotomy, and diabetes mellitus. Carbapenems, cephalosporins, quinolones, and aminoglycoside antimicrobials are the first-line drugs used clinically to treat KP infection [9]. In this study, the antimicrobial susceptibility of CRKP to carbapenems, cephalosporins, quinolones, aminoglycosides, sulfonamides and tetracycline is shown in Table 2. The majority of the CRKP strains were extremely resistant to commonly used noncarbapenem antibiotics. Even the three compounds with the greatest inhibitory activity, MNO, CSL and AMK, inhibited CRKP by only 30.95%, 24.0% and 20.73%, respectively. CRKP showed high resistance rates of 85.57%-100% to other β-lactam antibiotics, and CRKP also showed a high resistance rate to quinolones (85.71-100%) and aminoglycosides (95.74%). This suggests that quinolones, aminoglycosides, and other cephalosporin antimicrobials are not effective therapeutic options for CRKP-induced infections. The emergence of HVKP has led to increased difficulty in clinical treatment. The possibility of a hypervirulent pathogen that can infect healthy ambulatory individuals with severe infections is concerning. The frightening prospect of increased therapeutic difficulty due to the phenotypic characteristics of HVKP, which make it highly virulent, and the widespread evolutionary convergence of drug resistance acquired from cKP requires the immediate development of novel therapies against HVKP strains. Recognizing the virulence factors that cause the HVKP phenotype is an essential first step in this process. The best characterized virulence factors were capsule, lipopolysaccharide (LPS), iron uptake (also known as siderophores), and fimbriae [3]. Aerobactin ( iucA, iutA ), Ent siderophores ( fepA , entB ), Salmochelin ( iroB, iroN ), and Yersiniabactin ( ybtS ) are typically produced by HVKP [34]. The rmpA/rmpA2 gene-encoded HVKP gene is hypermucoviscous. fimH and mrkD mediate adhesion by encoding KP type 1 and type 3 fimbriae, and mrkD may promote the development of biofilms. Twenty-three (22.55%) of the 102 CRKP isolates tested positive for both the string test and gene markers. Capsule K1 was detected in 43.48% of the CR-HVKP strains, which was higher than that reported in a previous study [35]. The gene markers mrkD and fimH were detected in all the HVKP isolates. Clinicians should exercise caution when selecting an appropriate catheter and replace or irrigate it more frequently to minimize bacterial adhesion and colonization. The gene markers iroB and p rmpA2 were missing in all the isolates. The p rmpA was detected in only two HVKP strains (8.90%), suggesting that p rmpA was not the only factor contributing to high hypermucoviscosity. This finding is consistent with a previous study [36]. High prevalences of ybtS (100%), iucA (95.65%), entB (95.65%), iutA (91.30%), fepA (91.30%), and iroN (91.30%) were detected in this study. This suggests that factors associated with iron uptake, such as Aerobactin ( iucA , iutA ), Ent siderophores ( fepA , entB ), Salmochelin ( iroN ) and Yersiniabactin ( ybtS ), contribute significantly to the virulence of HVKP. These results are similar to those of previous studies [37, 38]. Key findings like 91.3% ST11 prevalence in CR-HVKP (Table 4) are contextualized with global studies, linking ST11 to IncFII plasmid-mediated resistance-virulence co-transfer, while mouse virulence data (LD50: 2×10³–5×10³ CFU) validate hypervirulent phenotypes against controls like NTUH-K2044. The identification of infections caused by CR-HVKP is a great challenge for physicians when administering clinical therapy, and the clarification of virulence factors and resistance mechanisms can aid in the selection of appropriate drugs. Chen et al. emphasize the role of hybrid plasmids in merging carbapenem resistance (CR) and hypervirulence (hv), a mechanism we observed in our ST11 CR-hvKP isolates carrying IncFII/IncR plasmids co-harboring bla KPC-2 and rmpA [39]. Carbapenemase production is the most important cause of carbapenem resistance in KPs. Carbapenemase enzymes, which are mostly encoded on plasmids and are highly transmissible, hydrolyse carbapenems [40]. Carbapenemases, a subset of β-lactamases, are classified into classes A, B, and D, with class C enzymes primarily hydrolyzing cephalosporins rather than carbapenems [41]. Class B carbapenemases (e.g., NDM, VIM), which are metallo-β-lactamases (MBLs), hydrolyze carbapenems using zinc-dependent mechanisms, distinct from serine-based class A/C/D carbapenemases [41]. KPC is a widespread class A enzyme [41]. All (class B) MBLs have the ability to produce carbapenemase, and this group also contains the acquired VIM, IMP, and NDM enzymes that may be present in a variety of gram-negative organisms [41]. Class D enzymes, commonly known as oxacillin carbapenemases [OXA enzymes], are a diverse collection of lactases with notable carbapenemase activity, particularly OXA-48-type enzymes in Enterobacterales and OXA-23 [42, 43], which are frequently detected in A. baumannii [44]. In this study, the carbapenem resistance genes detected in the CR-HVKP strain included bla KPC , bla VIM , bla SPM , bla GES , and bla NDM , with bla KPC being overwhelmingly predominant, which is consistent with the findings of a previous study in China [45]. The bla IMP and bla OXA-48 were not detected in any of the isolates. MLST revealed an overwhelming prevalence of ST11 among CR-HVKP strains in the present study. ST11 is a predominant sequence type in CR-HVKP, as reported in recent Chinese studies [46], reflecting its role in plasmid-mediated resistance-virulence co-transfer. Three pathways of PMQR (plasmid-mediated quinolone resistance) have been identified. DNA gyrase and topoisomerase IV are protected from quinolone inhibition by the pentapeptide repeat family of proteins, which is encoded by the plasmid genes qnrA , qnrB , qnrC , qnrD , qnrS and qnrE . A version of the common aminoglycoside acetyltransferase aac(6′)-Ib acetylates quinolones with a suitable amino nitrogen target in the second plasmid-mediated mechanism. The plasmid genes for the pumps QepAB and OqxAB cause greater efflux, which is the third mechanism. In this study, we found that the target genes mediating CR-HVKP resistance to quinolone were mainly aac(6')-Ib-cr, QnrS and QnrB , among which aac(6')-Ib-cr was detected in all the strains. Quinolone resistance was mediated by aac(6 ’ )-Ib-cr , qnrS , qnrB , and qnrE (rare), consistent with plasmid-mediated quinolone resistance (PMQR) mechanisms [47]. The mechanism of resistance to most aminoglycosides is associated with aminoglycoside-modifying enzymes (AMEs) [48], including acetyltransferases (AACs), nucleotidyltransferases (ANTs), and phosphotransferases (APHs), which vary in their ability to modify aminoglycosides. In addition, the overexpression of specific efflux pumps can lead to aminoglycoside resistance, and the gene encoding 16S rRNA methyltransferase (16S RMTase) can mediate high levels of resistance to aminoglycosides [49]. The target genes mediating CR-HVKP resistance to aminoglycosides identified in this study were mainly rmtB, ant(3'')-I and armA. The 16S RMTase-encoding genes rmtB and armA are the most common genes that confer high-level resistance to all clinically relevant aminoglycosides [50]. Notably, genes encoding methylases can be carried in integrons or transposons located in a variety of plasmids, which accelerates the rapid spread of the 16S-RMTase gene [51]. CR-HVKP has become a great challenge for antimicrobial chemotherapy, and aminoglycosides and quinolones combined with carbapenems are effective at reducing mortality. Unfortunately, our study revealed that almost all CR-HVKP strains were resistant to aminoglycosides and quinolones. Furthermore, conjugation assays revealed that virulence genes ( iucA, iutA, iroN and p rmpA ), genes mediating carbapenem resistance ( bla KPC , bla NDM , bla VIM , bla SHV and bla TEM ), genes mediating quinolone resistance ( QnrA, QnrB and QnrS ), and genes mediating aminoglycoside resistance ( rmtB ) can be transferred to E. coli J53. The results were generally consistent with those of previous studies [18, 52-56]. Compared with those of the recipient E. coli J53, the MICs of meropenem, imipenem, levofloxacin and amikacin in the transconjugants increased by 4-128 times. The genes fepA, entB, ybtS, mrkD, fimH, bla CTX-M2 , bla CTX-M9 , aac (6')-Ib-cr, ant(3'')-I, and OqxA were not transferred to E. coli J53. While conjugation was tested in two strains, the transfer of key resistance-virulence genes (Table 5) highlights potential for horizontal spread. As recent genomic studies of ST11-K1 CR-hvKP strains in China, which identified highly homologous bla KPC-2 -harbouring IncFII plasmids carrying conserved genetic structures (e.g., ISKpn6- bla KPC-2 -ISKpn27-ISYps3-IS26) [46]. New antimicrobial drugs that ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol can be used to treat infections in CRKP. Whereas only the ceftazidime-avibactam and eravacycline have been approved for use in China. The antimicrobials that tigecycline, fosfomycin, and colistin are still very important drugs for the treatment of CRKP in China. The susceptibility of the above CRKP and CR-HVKP strains to the important antimicrobials tigecycline, fosfomycin and polymyxin was further determined. According to the CLSI determination criteria, the above strains had good susceptibility to tigecycline but very low susceptibility to colistin and fosfomycin. Therefore, it is essential to further strengthen hospital infection prevention and control measures and to implement strict management and training regarding the appropriate use of antimicrobial medications in intensive care units. Conclusion In this study, CRKP strains were predominantly derived from sputum-, urine- and blood-specimens. Patients with CRKP infections predominantly had pulmonary infections. CRKP strains exhibit high resistance to other β-lactam antibiotics, quinolones and aminoglycosides. It is suggested that carbapenems in combination with aminoglycosides and quinolones, respectively, may not be an effective option for the treatment of CRKP infections. The LD50 of the CR-HVKP strains in the mice was similar to that of the positive control NTUH-K2044. Conjugation assays showed that some virulence genes and resistance genes can be transferred to E. coli J53. Compared with those of the recipient E. coli J53, the MICs of meropenem, imipenem, levofloxacin and amikacin in the transconjugants increased by 4-128 times. These findings suggest that these genes may spread rapidly in Enterobacterales, posing a public health risk and a significant threat to clinical care. Therefore, it is necessary to further strengthen hospital infection monitoring, prevention and control measures and to provide strict management and training on the rational use of antimicrobial agents in intensive care units. The resistance of CRKP and CR-HVKP to several new drugs, such as ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol, as well as the mechanism of resistance, need to be further investigated. Limitations Single-Center Scope: Our findings are derived from a single tertiary-care hospital, and the modest sample size (n =102) may limit generalisability. Multi-centre studies with larger cohorts are needed to confirm the prevalence of IncFII plasmid-mediated resistance-virulence co-transfer. Plasmid Characterisation: Plasmid sequencing was not performed to resolve the genetic architecture of resistance-virulence co-localisation. Future work will employ long-read sequencing to dissect plasmid structures and IS26-driven recombination events, as recently demonstrated in ST11-K1 CR-hvKP strains [46]. Functional Validation: Gene expression (e.g., virulence factors) in transconjugants was not assessed. Transcriptomic profiling under antibiotic stress will clarify regulatory dynamics in future studies. Abbreviations KP: Klebsiella pneumoniae CRKP : carbapenem-resistant Klebsiella pneumoniae HVKP: hypervirulent Klebsiella pneumoniae CR-HVKP : carbapenem-resistant hypervirulent Klebsiella pneumoniae MDR: Multidrug resistant XDR: widely drug resistant PDR: pan drug resistant MEM: meropenem IPM: imipenem Declarations Ethics approval and consent to participate Human Ethics Approval: The Ethics Committee of The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guizhou, China, provided ethical approval for the retrospective use of de-identified patient specimens and demographic data. Due to the observational nature of the study, informed consent was waived by the committee. Animal Ethics Approval: Animal studies were reviewed and approved by the Guizhou University Traditional Chinese Medicine Laboratory Animal Management Committee, ensuring compliance with the Guidelines for the Ethical Review of Laboratory Animal Welfare (People's Republic of China National Standard GB/T 35892-2018). All procedures were performed to minimize animal suffering, including the use of analgesics and humane endpoints as specified in the guidelines. Consent for publication Not applicable. Availability of data and materials All data generated or analysed during this study are included in this published article and its supplementary information files. The DNA sequencing data in the manuscript are present in [Virulence genes and resistance genes] repository. Competing interests The authors declare that they have no competing interests. Funding This work was supported by the National Natural Science Foundation of China (NSFC, 82460727); the Guizhou Provincial Basic Research Program (Natural Science), Grant No. Qiankehebasic-ZK [2022] General 501 and ZK [2019] General 1022; the Guizhou Provincial Department of Education, Young Science and Technology Talent Project, Grant No. Qianjiaohe KY [2022] 268; the Guizhou Provincial Health Commission, Science and Technology Fund Project, Grant No. gzwkj2021-395; the Guizhou Provincial Administration of Traditional Chinese Medicine, Grant No. QZYY-2024-016 and QZYY-2022-036; and the Talent research fund project of Anhui Agricultural University (No.rc392109). The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication. Authors' contributions XL performed virulence assay, mouse survival assay, analysed the data and wrote the manuscript. 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Coexistence of Multidrug Resistance and Virulence in a Single Conjugative Plasmid from a Hypervirulent Klebsiella pneumoniae Isolate of Sequence Type 25. mSphere. 2022;7(6):e0047722; doi: 10.1128/msphere.00477-22. Li X, Jiang T, Wu C, Kong Y, Ma Y, Wu J, et al. Molecular epidemiology and genomic characterization of a plasmid-mediated mcr-10 and bla(NDM-1) co-harboring multidrug-resistant Enterobacter asburiae. Comput Struct Biotechnol J. 2023;21:3885-93; doi: 10.1016/j.csbj.2023.08.004. Girijan SK, Paul R, V JR, Pillai D. Investigating the impact of hospital antibiotic usage on aquatic environment and aquaculture systems: A molecular study of quinolone resistance in Escherichia coli. Sci Total Environ. 2020;748:141538; doi: 10.1016/j.scitotenv.2020.141538. Deng YT, Zeng ZL, Tian W, Yang T, Liu JH. Prevalence and characteristics of rmtB and qepA in Escherichia coli isolated from diseased animals in China. Front Microbiol. 2013;4:198; doi: 10.3389/fmicb.2013.00198. Yang Y, Zhang A, Lei C, Wang H, Guan Z, Xu C, et al. Characteristics of Plasmids Coharboring 16S rRNA Methylases, CTX-M, and Virulence Factors in Escherichia coli and Klebsiella pneumoniae Isolates from Chickens in China. Foodborne Pathog Dis. 2015;12(11):873-80; doi: 10.1089/fpd.2015.2025. Additional Declarations No competing interests reported. Supplementary Files SupplementaryFileS2Virulencegenesandresistancegenesrepository1.docx SupplementaryFileS1.docx Cite Share Download PDF Status: Published Journal Publication published 06 Jun, 2025 Read the published version in BMC Microbiology → Version 1 posted Editorial decision: Revision requested 08 May, 2025 Editor assigned by journal 08 May, 2025 Reviews received at journal 07 May, 2025 Reviews received at journal 04 May, 2025 Reviewers agreed at journal 28 Apr, 2025 Reviewers agreed at journal 25 Apr, 2025 Reviewers agreed at journal 24 Apr, 2025 Reviewers invited by journal 24 Apr, 2025 Submission checks completed at journal 24 Apr, 2025 First submitted to journal 23 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5028260","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":447287747,"identity":"c6082024-eb45-4bbd-b584-15f27856f13e","order_by":0,"name":"Xue Li","email":"","orcid":"","institution":"Guizhou University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xue","middleName":"","lastName":"Li","suffix":""},{"id":447287748,"identity":"4f85cc2c-d36b-46f8-a34c-2a6064c6618d","order_by":1,"name":"Kai Ma","email":"","orcid":"","institution":"University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kai","middleName":"","lastName":"Ma","suffix":""},{"id":447287750,"identity":"0ab64368-4805-4fbf-b215-9b9fc93527ce","order_by":2,"name":"Xin Liu","email":"","orcid":"","institution":"Guizhou University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Liu","suffix":""},{"id":447287752,"identity":"b33c8d4f-548b-4940-b1b1-f9a25f9707e0","order_by":3,"name":"Ping Cheng","email":"","orcid":"","institution":"Anhui Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"Cheng","suffix":""},{"id":447287753,"identity":"8943b830-e981-4269-ad24-68c55a3bf78b","order_by":4,"name":"Lailai Li","email":"","orcid":"","institution":"Guizhou University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Lailai","middleName":"","lastName":"Li","suffix":""},{"id":447287754,"identity":"2e26c02f-431a-493c-8da0-422df672e00e","order_by":5,"name":"Yihui Chai","email":"","orcid":"","institution":"Guizhou University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yihui","middleName":"","lastName":"Chai","suffix":""},{"id":447287755,"identity":"6e130c89-c346-4a33-b2ac-6bd8ac4cce8e","order_by":6,"name":"Mingle Cao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA10lEQVRIiWNgGAWjYNCCAgk5fvbmAwc+/CBai4GNsWTPscSDM3uI15KWuOFGjvFhDjYiFMv7nzH8dMPgcGLDjZwPhxl4GOT5xQ7g12J44IyxdI7BYePGnrcbDhdYMBjOnJ1AQEtjjxkzUItsM3vuhsMzeBgSDG4T0tLMA9bC2MaQ8+AwDxsRWuTZwFrSFHs4chiI02LAw1YM9IuNsQTPMQNgIEsQ9ot8/+GNn3MqJOTsjzc//vDhh408vzQhWw5wGCDzJfArB9vSwP6AsKpRMApGwSgY2QAAxP9HCY+1FT8AAAAASUVORK5CYII=","orcid":"","institution":"Affiliated Duyun Hospital of Qiannan Medical College.","correspondingAuthor":true,"prefix":"","firstName":"Mingle","middleName":"","lastName":"Cao","suffix":""},{"id":447287756,"identity":"c1be828e-5575-479b-b5b7-79bdfd5de60d","order_by":7,"name":"Yuqi Yang","email":"","orcid":"","institution":"Guizhou University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuqi","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2024-09-04 03:21:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5028260/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5028260/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12866-025-04052-x","type":"published","date":"2025-06-06T15:57:17+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82023031,"identity":"e28813eb-36d0-4ecc-9357-e30ef55fd60b","added_by":"auto","created_at":"2025-05-06 06:06:53","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":110805,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival of Kunming mice (KM) after intraperitoneally (IP) challenge with NTUH-K2044, KP66974, KP62811, KP65640, KP55182 and HS11286. (A) The mice were challenged with 10\u003csup\u003e3-5\u003c/sup\u003e CFU of NTUH-K2044. (B) The mice were challenged with 10\u003csup\u003e3-5\u003c/sup\u003e CFU of KP66974. (C) The mice were challenged with 10\u003csup\u003e3-5\u003c/sup\u003e CFU of KP62811. (D) The mice were challenged with 10\u003csup\u003e3-5\u003c/sup\u003e CFU of KP65640. (E) The mice were challenged with 10\u003csup\u003e3-7\u003c/sup\u003e CFU of KP55182 and HS11286. ns, not significantly different.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5028260/v1/6ee402535eb21fcfe155417f.jpg"},{"id":82023036,"identity":"8253ba1b-395f-4a47-9d7d-6883ea4f9b90","added_by":"auto","created_at":"2025-05-06 06:06:53","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":291385,"visible":true,"origin":"","legend":"\u003cp\u003eGenes mediating CR-HVKP resistance to carbapenems, cephalosporins, quinolones, aminoglycosides and sulphonamides. Green is used to represent positive results, indicating the presence of genes mediating resistance, while gray represents negative results, signifying the absence of such genes.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5028260/v1/96c8988d56f12fc09ea913d1.jpg"},{"id":84242658,"identity":"da436ab1-7fcf-49ba-b718-29771a1f1d36","added_by":"auto","created_at":"2025-06-09 16:10:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2095832,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5028260/v1/94f63b85-b6ea-4784-832c-c4f487225ba5.pdf"},{"id":82024098,"identity":"5df9d79e-d23f-4610-a264-741badcbf66a","added_by":"auto","created_at":"2025-05-06 06:22:53","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":27907,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFileS2Virulencegenesandresistancegenesrepository1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5028260/v1/630daccf0bff8f3357f87851.docx"},{"id":82023034,"identity":"6d34567e-6ecf-4e9e-87a7-f136a2ebaf13","added_by":"auto","created_at":"2025-05-06 06:06:53","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":68457,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFileS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5028260/v1/596720e924342dae9f54512b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prevalence and molecular characterisation of multi-drug resistant ST11 hypervirulent Klebsiella pneumoniae in a teaching hospital","fulltext":[{"header":"Background","content":"\u003cp\u003e\u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e (\u003cem\u003eK.\u003c/em\u003e\u003cem\u003epneumoniae,\u0026nbsp;\u003c/em\u003eKP) is a common cause of community-associated and nosocomial bacteraemia [1]. In immunocompromised individuals, such as those with diabetes or cancer, KP is an opportunistic pathogen that can cause a variety of diseases, including pneumonia, bacteremia, urinary tract infections, and meningitis. The subsequent spread of KP into the blood, which results in bacteremia, is a very serious side effect of KP pneumonia and UTIs [2]. KP can be divided into two groups, classical KP (cKP) and hypervirulent KP (HVKP), according to their pathogenicity. HVKP is distinguished from classical KP (cKP) by its enhanced pathogenicity, primarily driven by unique virulence factors such as capsular polysaccharides (e.g., K1, K2 serotypes), iron-uptake systems (aerobactin, yersiniabactin), and regulatory genes (\u003cem\u003ermpA\u003c/em\u003e). While cKP may possess basic virulence traits like fimbriae (\u003cem\u003efimH\u003c/em\u003e), HVKP uniquely harbors hypermucoviscosity-associated genes (\u003cem\u003ermpA\u003c/em\u003e) and specialized siderophores (e.g., \u003cem\u003eiucA\u003c/em\u003e, \u003cem\u003eiroN\u003c/em\u003e), enabling invasive infections in immunocompetent hosts. The development and spread of HVKP has increased the range of individuals who are susceptible to infections, including those with adequate immune systems and good health [3]. The best characterized virulence factors were capsule, lipopolysaccharide (LPS), iron uptake (also known as siderophores), and fimbriae [3]. The string test has been used frequently to identify HVKP strains, and hypervirulence has been indicated by hypermucoviscosity [4]. Hypermucoviscosity is characterized as a positive string test by stretching a KP colony with a bacteriological loop on an agar plate, which manifests as a viscous filament greater than 5 mm in length [4], while not all hypervirulent strains exhibit the hypermucoviscous phenotype, and not all hypermucoviscous strains lead to an invasive syndrome [5]. The most common HVKP serotypes include K1, K2, K20, K54, and K57, with K1 and K2 being the most virulent, accounting for 70% of HVKP isolates [6].\u003c/p\u003e\n\u003cp\u003eMultidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug resistant (PDR) isolates were classified as those that were resistant to at least one antibiotic in three or more classes, at least one antibiotic in all but two or fewer classes, and all drugs tested across all major antimicrobial classes. [7]. With the emergence of MDR, XDR and PDR-KP, choosing the appropriate antibiotic prescription to treat infections can be difficult for physicians given that patients often present with serious infections and complications [8]. As carbapenems have been the standard treatment approach for the systemic treatment of serious infections caused by gram-negative bacteria, carbapenem resistance presents new and difficult challenges in therapeutic decision-making, particularly because of the high frequency of co-resistance. An overview of the treatment options for selected pathogens and patterns of resistance was reported in previous literature [9]. Clinical isolates of metallo-beta-lactamase (MBL)-producing or KPC-producing\u003cem\u003e\u0026nbsp;K. pneumoniae\u003c/em\u003e are susceptible to quinolones and aminoglycosides and can be treated with quinolones or aminoglycosides in combination with meropenem. However, if the clinical strain is resistant to quinolones and aminoglycosides, tigecycline, colistin or fosfomycin is chosen in combination with meropenem [9]. Recent studies highlight the rising prevalence of quinolone (e.g., \u003cem\u003eaac(6\u003c/em\u003e\u003cem\u003e’\u003c/em\u003e\u003cem\u003e)-Ib-cr\u003c/em\u003e, \u003cem\u003eqnrS\u003c/em\u003e) and aminoglycoside (e.g., \u003cem\u003ermtB\u003c/em\u003e, \u003cem\u003earmA\u003c/em\u003e) resistance in carbapenemase-producing Enterobacterales.\u003c/p\u003e\n\u003cp\u003eEvidence suggests that patients who are infected by carbapenem-resistant pathogens have an increased likelihood of morbidity and mortality compared with those infected by susceptible pathogens [10-12], which is likely due to the administration of antibiotics with suboptimal or no activity against these organisms [13]. Thus, recognizing the risk of carbapenem resistance, particularly in the most vulnerable patient populations [14, 15], and/or early detection of specific carbapenem resistance mechanisms [16] are critical to reduce the risk of mortality, length of hospitalization, and associated costs [12]. Enterobacterales pathogens resistant to carbapenem (CRE) have been placed in the highest priority category in the 2024 Global Priority Pathogens List published by the World Health Organization (i.e., critical) [17]. Identification and ongoing monitoring of CRE are needed to address this global epidemic.\u003c/p\u003e\n\u003cp\u003eIn this study, we carried out (1) the susceptibility of nosocomial KP strains to antimicrobial drugs such as β-lactams, carbapenems, quinolones, tetracyclines, aminoglycosides, polymyxins, and sulfonamides; (2) the resistance phenotypes of 102 CRKP strains and the clinical characteristics of patients with CRKP infections; (3) the virulence factors mediating the high virulence of CR-HVKP strains and the virulence factors mediating the high virulence of CR-HVKP strains; (4) the multilocus sequence typing and resistance genes mediating the resistance of CR-HVKP strains to carbapenems, aminoglycosides, quinolones, and sulfonamides; and (5) the susceptibility of CRKP and CR-HVKP strains to tigecycline, colistin, and fosfomycin to support clinicians in drug selection and regimen development for the treatment of nosocomial CRKP and CR-HVKP-induced infections.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eSpecies identification and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eantimicrobial\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;susceptibility\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIsolates were collected from The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, a tertiary-care university teaching hospital with 2629 beds serving diverse clinical departments. All 674 KP isolates were identified in the clinical laboratory\u0026nbsp;from December 2020 to January 2022 using colony morphology, Gram stain, biochemical tests, and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (TECO-HYGI Mass Spectrometer EXS3000, China) in accordance with the manufacturer\u0026rsquo;s instructions. Antimicrobial susceptibility testing (AST) was performed using the Vitek 2 system (bioM\u0026eacute;rieux, Marcy-l\u0026rsquo;\u0026Eacute;toile, France) \u0026nbsp;for initial screening, with confirmatory broth microdilution for critical antibiotics (e.g., carbapenems, fosfomycin) following CLSI M100-S34 guidelines. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of imipenem (IPM), meropenem (MEM), ertapenem (ETP), ampicillin/Sulbactam (SAM), cefazolin (CZO3), cefotetan (CTT), ceftriaxone (CRO), piperacillin/tazobactam (TZP), ceftazidime (CAZ), cefepime (FEP), ampicillin (AMP), amoxicillin/clavulanic acid (AMC), ticarcillin (TIC), piperacillin (PIP), cefalotin (CFT), cefazolin (CZO), cefuroxime (CXM), aztreonam (ATM), cefoxitin (FOX), cefixime (CFM), cefotaxime (CTX), cefoperazone/sulbactam (CSL), nalidixic acid (NAL), ofloxacin (OFX), ciprofloxacin (CIP), levofloxacin (LVX), nitrofurantoin (NIT), tetracycline (TCY), compound trimethoprim (SXT), gentamicin (GEN), tobramycin (TOB), amikacin (AMK), and cefuroxime axetil. K-B silver diffusion was performed with minocycline. The production of extended-spectrum \u0026beta;-lactamase (ESBL) was tested in all the strains. Extended-spectrum\u0026nbsp;\u0026beta;-lactamase (ESBL) production was detected using the combined disk synergy test (CDST) with cefotaxime/clavulanic acid and ceftazidime/clavulanic acid, per CLSI M100-S34 criteria, with cefotaxime (30 \u0026mu;g) and ceftazidime (30 \u0026mu;g) disks alone and in combination with clavulanic acid (10 \u0026mu;g). A \u0026ge;5 mm increase in the inhibition zone diameter with clavulanic acid was considered positive for ESBL production\u0026nbsp;[4].\u0026nbsp;\u003cem\u003eEscherichia coli\u0026nbsp;\u003c/em\u003eATCC 25922 and \u003cem\u003eK. pneumoniae\u003c/em\u003e ATCC 700603 were used as controls and obtained from the American Type Culture Collection (ATCC). AST results were interpreted using CLSI M100-S34 breakpoints\u0026nbsp;[18]. The MIC\u003csub\u003e50\u003c/sub\u003e and MIC\u003csub\u003e90\u003c/sub\u003e of each antibiotic were defined as the lowest concentration of the antibiotic required to inhibit 50 and 90% of isolates, respectively. The isolates were defined as CRKP if they were resistant to at least one of the carbapenem agents, including imipenem, ertapenem, and meropenem. A total of 102\u0026nbsp;nonrepetitive\u0026nbsp;clinical CRKP isolates were used in further studies\u0026nbsp;[18].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, clinical data from 674 patients with \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e (KP) infection were retrospectively reviewed, of whom 102 had isolates demonstrating carbapenem resistance (CRKP). Information on 102 patients with CRKP infection was statistically analysed. In addition to demographic information such as age, sex, and basic medical history, the survey also asked about hospitalization features such as sample source and department of separation, among others. Noninfected patients whose clinical samples were taken as part of the standard hospital laboratory practice were excluded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVirulence assay\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eK. pneumoniae\u003c/em\u003e was isolated from patient samples and identified using accepted clinical microbiologic techniques (CLSI, 2024). The string test was carried out by touching a colony with a loop and tugging up after inoculation on TSB agar plates and overnight incubation at 37℃. The string test was determined\u0026nbsp;to be\u0026nbsp;positive when a viscous string over 5 mm in length\u0026nbsp;was produced\u0026nbsp;[19]. Twenty-three carbapenem-resistant CRKP isolates positive for the string test, a phenotypic marker of hypermucoviscosity, were selected from the study. Strains\u0026nbsp;NTUH-K2044 and HS11286\u0026nbsp;were\u0026nbsp;used as positive\u0026nbsp;controls\u0026nbsp;and negative\u0026nbsp;controls, respectively. The best characterized virulence factors,\u0026nbsp;Aerobactin (\u003cem\u003eiucA, iutA\u003c/em\u003e), Ent siderophore (\u003cem\u003efepA, entB\u003c/em\u003e), Salmochelin (\u003cem\u003eiroB, iroN\u003c/em\u003e), Yersiniabactin (\u003cem\u003eybtS\u003c/em\u003e), Type 3 fimbriae (\u003cem\u003emrkD\u003c/em\u003e), Type I fimbriae (\u003cem\u003efimH\u003c/em\u003e), Regulation\u0026nbsp;(\u003cem\u003e\u003csub\u003ep\u003c/sub\u003e\u003c/em\u003e\u003cem\u003ermpA, \u003csub\u003ep\u003c/sub\u003ermpA2, \u003csub\u003ec\u003c/sub\u003ermpA\u003c/em\u003e), and Capsular serotype-specific\u0026nbsp;genes (K1, K2, K5, K20, K54, K57, K47 and K64),\u0026nbsp;were detected by\u0026nbsp;polymerase\u0026nbsp;chain reaction (PCR)\u0026nbsp;[20, 21]. Virulence genes were detected via PCR using primers listed in Supplementary Table S1. PCR products were sequenced using Sanger sequencing (Illumina NextSeq 500 platform), with sequence alignment and interpretation via BLAST on the NCBI database. Genomic sequences were analyzed using the Basic Local Alignment Search Tool (BLAST) suite (NCBI, USA) to identify virulence factors. Nucleotide and protein sequences were queried against the NCBI Nucleotide (nt) databases. BLASTp was employed for virulence factor annotation using the Virulence Factors of Pathogenic Bacteria database (VFDB).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMouse\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;survival assay\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mouse survival assay was performed as described previously [20] with a minor modification to define the inoculum volume and optimize animal welfare. Four KP\u0026nbsp;isolates were used in\u0026nbsp;the mouse\u0026nbsp;survival assay:\u0026nbsp;KP66974, KP62811, KP65640\u0026nbsp;and\u0026nbsp;KP55182. Strains were selected for gene analysis if they were CR-HVKP (string test-positive + core virulence genes: \u003cem\u003ermpA, iucA, iroN\u003c/em\u003e). KP\u0026nbsp;strains\u0026nbsp;NTUH-K2044 (phenotype pattern of ST23, K1, \u003cem\u003eallS, peg-344, wzy-K1, entB, irp2, iroN, iucA, fimH, mrkD, \u003csub\u003ec\u003c/sub\u003ermpA, \u003csub\u003ep\u003c/sub\u003ermpA, \u003csub\u003ep\u003c/sub\u003ermpA2, wzi\u003c/em\u003e, GenBank accession NC_012731) and HS11286 (phenotype pattern of ST11, K47, \u003cem\u003eentB, irp2, fimH, mrkD, wzi\u003c/em\u003e, GenBank accession NC_016845)\u0026nbsp;were\u0026nbsp;used as positive\u0026nbsp;controls\u0026nbsp;and low-virulence\u0026nbsp;controls, respectively. In brief, male specific pathogen-free (SPF) Kunming mice (18 to 20 g; n = 6 per group) were injected\u0026nbsp;intraperitoneally\u0026nbsp;with various titres of the 200\u0026nbsp;\u0026micro;L bacterial strains being assessed. The study endpoint, significant illness (in an extreme state), or death\u0026nbsp;was\u0026nbsp;observed in the animals for a maximum of seven days. For all six KP\u0026nbsp;strains, a challenge inoculum of 2 \u0026times; 10\u003csup\u003e3\u003c/sup\u003e to 5 \u0026times; 10\u003csup\u003e3\u003c/sup\u003e CFU was initially used for all strains, with sequential challenges of 3 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e to 5 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e CFU and 3 \u0026times; 10\u003csup\u003e7\u003c/sup\u003e to 6 \u0026times; 10\u003csup\u003e7\u003c/sup\u003e CFU if all animals in the group survived a given challenge inoculum. The survival rate of\u0026nbsp;the\u0026nbsp;mice was recorded at 1, 2, 3, 4, 5, 6,\u0026nbsp;and\u0026nbsp;7 days. All the surviving mice were euthanized under isoflurane anesthesia in order to alleviate the pain.\u0026nbsp;K‒M\u0026nbsp;survival curves were plotted using GraphPad Prism\u0026nbsp;[20, 22].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMolecular Detection of Antibiotic Resistance Genes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePCR was performed to detect common carbapenem resistance genes (carbapenemase, \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eKPC\u003c/sub\u003e and \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eGES\u003c/sub\u003e, metalloenzyme, \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eNDM\u003c/sub\u003e, \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eVIM\u003c/sub\u003e, \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eIMP\u003c/sub\u003e and \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eSPM\u003c/sub\u003e,oxacillinase,\u003cem\u003e\u0026nbsp;bla\u003c/em\u003e\u003csub\u003eOXA-48\u003c/sub\u003e), ESBLs (\u003cem\u003ebla\u003c/em\u003e\u003csub\u003eSHV\u003c/sub\u003e, \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eTEM\u003c/sub\u003e, \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eCTX-M1\u003c/sub\u003e, \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eCTX-M2\u003c/sub\u003e, \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eCTX-M8\u003c/sub\u003e, \u003cem\u003ebla\u003c/em\u003e\u003csub\u003eCTX-M9\u003c/sub\u003e), plasmid-mediated quinolone resistance genes (5 quinolone resistance proteins, \u003cem\u003eqnrA, qnrB, qnrC, qnrD and qnrS\u003c/em\u003e, one quinolone-modifying enzyme, \u003cem\u003eaac(6\u0026apos;)-Ib-cr\u003c/em\u003e, encoding quinolone efflux pump proteins, \u003cem\u003eqep, oqxA and oqxB\u003c/em\u003e), encoding AME genes (\u003cem\u003eaac(3\u0026apos;)-II, aac(6\u0026apos;)-Ib, aac(6\u0026apos;)-II, ant(3\u0026apos;\u0026apos;)-I, aph(3\u0026apos;)-VI\u003c/em\u003e),\u0026nbsp;encoding 16S rRNA methyltransferases (\u003cem\u003earmA\u003c/em\u003e and \u003cem\u003ermtB\u003c/em\u003e), conferring high-level aminoglycoside resistance,\u0026nbsp;and\u0026nbsp;sulfonamide determinants (\u003cem\u003esul1\u003c/em\u003e,\u003cem\u003e\u0026nbsp;sul2\u003c/em\u003e). The primer sequences and amplicon sizes are shown in Supplementary Table S2. Antimicrobial resistance (AMR) genes were screened in all 102 CRKP isolates using PCR. Using the NextSeq 500 sequencing platform, the positive PCR products were sequenced (Illumina, San Diego, CA, USA). BLAST was used to compare nucleotide sequences on the NCBI website (http://blast.ncbi.nlm.nih.gov/Blast.cgi).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConjugation assay\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA conjugation assay was carried out to investigate whether these virulence genes and resistance genes could be transferred. Donor isolates were selected based on their divergent virulence phenotypes in mouse survival assays: KP66974 (\u0026le;33.33% survival at 2 \u0026times; 10\u0026sup3;\u0026ndash;5 \u0026times; 10\u0026sup3; CFU) and KP65640 (100% survival at 2 \u0026times; 10\u0026sup3;\u0026ndash;5 \u0026times; 10\u0026sup3; CFU), to investigate whether transferable genetic elements underlie the acquisition of hypervirulence and resistance during conjugation. \u0026nbsp;The \u003cem\u003eE. coli\u003c/em\u003e J53 as recipient isolate. The donors and recipients were cultured in Luria\u0026ndash;Bertani (LB) broth (37℃) to the logarithmic phase. The donors\u0026nbsp;and recipients were mixed\u0026nbsp;at\u0026nbsp;a 2:1 ratio, centrifuged at 8,000\u0026nbsp;\u0026times;\u0026nbsp;g for 1 min, and resuspended in 20 mL of MgSO4 (10 mM).\u0026nbsp;The\u0026nbsp;resuspension\u0026nbsp;was spread\u0026nbsp;evenly on LB plates and\u0026nbsp;incubated\u0026nbsp;at 37℃\u0026nbsp;overnight. Subsequently, the serial dilutions were plated in media\u0026nbsp;supplemented\u0026nbsp;with\u0026nbsp;the\u0026nbsp;appropriate antibiotics (meropenem, 32 mg/L;\u0026nbsp;levofloxacin, 8 mg/L;\u0026nbsp;amikacin, 64 mg/L;\u0026nbsp;and\u0026nbsp;sodium azide, 100 mg/L)\u0026nbsp;[23]. Transconjugants were selected on LB plates containing meropenem (32 mg/L), levofloxacin (8 mg/L), amikacin (64 mg/L), and sodium azide (100 mg/L) simultaneously, to ensure acquisition of all target resistance genes. Antimicrobial susceptibility, PCR, and DNA sequencing were used to confirm the presence of the \u003cem\u003eiucA, iutA, iroN, \u003csub\u003ep\u003c/sub\u003ermpA, bla\u003csub\u003eKPC\u003c/sub\u003e, bla\u003csub\u003eNDM\u003c/sub\u003e, bla\u003csub\u003eVIM\u003c/sub\u003e, bla\u003csub\u003eTEM\u003c/sub\u003e, bla\u003csub\u003eGES\u003c/sub\u003e, bla\u003csub\u003eSHV\u003c/sub\u003e, bla\u003csub\u003eCTX-M2\u003c/sub\u003e, bla\u003csub\u003eCTX-M9\u003c/sub\u003e, ant (3\u0026apos;\u0026apos;)-I, OqxA, rmtB, aac (6\u0026apos;)-Ib-cr, QnrA, QnrB,\u003c/em\u003e \u003cem\u003eQep, fepA, entB, ybtS, mrkD, fimH,\u003c/em\u003e and\u003cem\u003e\u0026nbsp;QnrS\u003c/em\u003e genes in\u0026nbsp;the transconjugants. All primers\u0026nbsp;used\u0026nbsp;are\u0026nbsp;listed\u0026nbsp;in Supplementary Table S1 and Table S2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMultilocus Sequence Typing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMultilocus sequence typing (MLST) was performed on all 23 CR-HVKP isolates to determine genetic relatedness. MLST of CR-HVKPwas performed according to previously described methods [24]. Seven conserved housekeeping genes (\u003cem\u003egapA, infB, mdh, pgi, phoE, rpoB, and tonB\u003c/em\u003e) were amplified, sequenced, and compared with those in the MLST databases (https://pubmlst.org/). The primer sequences and amplicon sizes are listed in Supplementary Table S3.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAntimicrobial susceptibility of CRKP and CR-\u003c/strong\u003eHVKP\u003cstrong\u003e\u0026nbsp;to\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003etigecycline\u003c/strong\u003e\u003cstrong\u003e, colistin and fosfomycin\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe broth microdilution method (tigecycline and colistin) or agar dilution (fosfomycin) was used to determine the MICs\u0026nbsp;for CR-HVKP and CRKP according to the standard protocols of the CLSI guidelines [18]. CLSI M100-S34 breakpoints were used for all antibiotics, except tigecycline, which followed EUCAST guidelines (\u0026le;2 \u0026micro;g/mL susceptible). Isolates with\u0026nbsp;MICs\u0026nbsp;\u0026ge;4 \u0026micro;g/mL for colistin, and \u0026ge;256 \u0026micro;g/mL for fosfomycin were considered resistant\u0026nbsp;[18].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTheStatistical Package for the Social Sciences (SPSS) version 22.0 was used to conduct a descriptive analysis utilizing mean, percentage, and frequency statistics (IBM Corporation, Armonk, NY, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eBacterial isolates\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eK. pneumoniae\u003c/em\u003e resistance to carbapenems is defined as resistance to imipenem, meropenem or ertapenem. In total, 102 CRKP strains were identified from 674 (15.13%) KP strains collected from December 2020 to January 2022. The clinical characteristics of the 102 patients with CRKP infections are presented in Table 1. The mean\u0026plusmn;SD age of patients with CRKP infection was 75.89\u0026plusmn;16.17 (4-104 years), with an absolute male predominance of 76.47% (n=78). The CRKP strains were mainly derived from sputum specimens (68 strains, 66.67%), urine specimens (17 strains, 16.67%) and blood specimens (5 strains, 4.90%). Patients with CRKP infection were mainly located in intensive care units (ICUs, 55.88%), respiratory medicine units (PCCMs, 14.71%), and general surgery units (11.76%). The clinical diagnoses were mostly pulmonary infection, including community-acquired pneumonia (n=28, 27.45%), severe pneumonia (n=19, 18.63%), chronic obstructive pulmonary disease (n=15, 14.71%) and pneumonia (n=12, 11.76%).\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"336\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Clinical characteristics of patients with CRKP infections\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003en(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eDemographics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eage (years), mean\u0026plusmn;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e75.89\u0026plusmn;16.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e78 (76.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eLocation at time of culture\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eIntensive Care Medicine (ICU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e57 (55.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eRespiratory Medicine (PCCM)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15 (14.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGeneral Surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12 (11.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eEmergency Medicine Ward\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7 (6.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGastroenterology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4 (3.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eHematology Ward\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3 (2.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eOrthopedic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3 (2.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePediatrics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1 (0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eInfection source\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSputum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e68 (66.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eUrine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e17 (16.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eBlood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5 (4.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eBronchoalveolar lavage solution\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4 (3.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePharyngeal swab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2 (1.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDecubitus ulcers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2 (1.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSecretions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2 (1.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCatheter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1 (0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePeritoneal puncture fluid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1 (0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCommunity-acquired pneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e28 (27.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSevere pneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e19 (18.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eChronic obstructive pulmonary disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15 (14.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12 (11.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSepticemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10 (9.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCerebral hemorrhage recovery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7 (6.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCerebral infarction sequelae\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4 (3.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eType 2 diabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3 (2.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eGallbladder stones\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2 (1.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDementia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1 (0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eEpilepsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1 (0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eAntimicrobial susceptibility\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe antimicrobial susceptibility of CRKP to carbapenems, cephalosporins, quinolones, aminoglycosides, sulfonamides and tetracycline is shown in Table 2. The resistance rates of CRKP to imipenem, meropenem and ertapenem were 82.98%, 79.52% and 73.58%, respectively. The carbapenem-resistant isolates had MICs ranging from 0.25 to \u0026gt;16 mg/L, MIC\u003csub\u003e50\u003c/sub\u003e \u0026gt;16 mg/L, and MIC\u003csub\u003e90\u003c/sub\u003e \u0026gt;16 mg/L for imipenem; MICs ranging from 0.0625 to \u0026gt;32 mg/L, MIC\u003csub\u003e50\u003c/sub\u003e \u0026gt;32 mg/L, and MIC\u003csub\u003e90\u003c/sub\u003e \u0026gt;32 mg/L for meropenem; and MICs ranging from 0.12 to \u0026gt;8 mg/L, MIC\u003csub\u003e50\u003c/sub\u003e \u0026gt;8 mg/L, and MIC\u003csub\u003e90\u003c/sub\u003e \u0026gt;8 mg/L for ertapenem. Even the three compounds with the greatest inhibitory activity, MNO, CSL and AMK, inhibited CRKP by only 30.95%, 24.0% and 20.73%, respectively. In contrast, 85.57%-100% of CRKP strains were resistant to the other \u0026beta;-lactam antibiotics SAM (100%), CZO3 (100%), CTT (94.87%), CRO (95.6%), TZP (86.59%), CAZ (91.84%), FEP (85.57%), AMP (100%), AMC (91.23%), TIC (100%), PIP (100%), CFT (100%), CZO (100%), CXM (93.10%), ATM (95.74%), FOX (86.21%), CFM (100%), CTX (100%) and CXA (91.84%). The CRKP strains also exhibited high resistance rates to quinolones NAL (85.71%), OFX (87.50%), CIP (93.62%), LVX (91.84%), NIT (95%), TCY (100%), and SXT (88.89) and aminoglycosides GEN (95.74%) and TOB (95.74%). Resistance profile of 23 CR-HVKP is present in Table 3. Most of CR-HVKP strains are XDR, three of the CR-HVKP strains also produced ESBL. Overall, CRKP strains are highly resistant to cephalosporins, quinolones, aminoglycosides, tetracyclines, sulfonamides.\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"631\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 99.8542%;\" colspan=\"8\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Antimicrobial susceptibility of CRKP to Carbapenems, cephalosporins, quinolones, aminoglycosides, sulfonamides, tetracycline\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntibiotic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003e\u003cstrong\u003esubclasses\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eI(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eS(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMIC\u003csub\u003e50\u0026nbsp;\u003c/sub\u003e(mg/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMIC\u003csub\u003e90\u0026nbsp;\u003c/sub\u003e(mg/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMIC range (mg/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026beta;-Lactams\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eIPM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e82.98(78/94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e17.02(16/94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e0.25 to \u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eMEM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e79.52(66/83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e6.02(5/83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e14.46(12/83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e0.0625 to \u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eETP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e73.58(39/53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1.89(1/53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e24.53(13/53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e0.12 to \u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eSAM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e100(39/39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0(0/39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eCZO3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e100(8/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0(0/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eCTT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e94.87(37/39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e5.13(2/39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e4 to \u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eCRO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e95.6(87/91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e4.4(4/91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e0.25 to \u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eTZP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e86.59(71/82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e3.66(3/82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e9.76(8/82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;128\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e4 to \u0026gt;128\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eCAZ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e91.84(90/98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e8.16(8/98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e0.12 to \u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eFEP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e85.57(83/97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e7.22(7/97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e7.22(7/97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e0.12 to \u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eAMP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e100(29/29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0(0/29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e16 to \u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eAMC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e91.23(52/57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e8.77(5/57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e2 to \u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eTIC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e100(7/7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0(0/7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003ePIP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e100(8/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0(0/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eCFT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e100(7/7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0(0/7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eCZO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e100(33/33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0(0/33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e4 to \u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eCXM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e93.10(54/58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e6.90(4/58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e1 to \u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eATM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e95.74(45/47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e4.26(2/47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e2 to \u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eFOX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e86.21(50/58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e13.79(8/58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e4 to \u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eCFM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e100(8/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0(0/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eCTX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e100(7/7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0(0/7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eCSL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e76.00(57/75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e24.00(18/75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e8 to \u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eCXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e91.84(45/49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e8.16(4/49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e1 to \u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eQuinolones\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eNAL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e85.71(6/7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e14.29(1/7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e16 to 32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eOFX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e87.50(7/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e12.50(1/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e2 to 4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eCIP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e93.62(44/47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e6.38(3/47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e0.25 to 4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eLVX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e91.84(90/98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e2.04(2/98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e6.12(6/98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e0.12 to 8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eNIT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e95.00(19/20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e5.00(1/20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0(0/20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026gt;512\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026gt;512\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e64 to \u0026gt;512\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eTetracyclines\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eTCY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e100(8/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0(0/8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eMNO ND30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e17.86(15/84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e51.19(43/84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e30.95(26/84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eTigecycline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e1.27 (1/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e2.53 (2/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e96.20 (76/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e0.25 to 16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eSulfonamides\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eSXT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e88.89(80/90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e11.11(10/90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026gt;320\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026gt;320\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e20 to \u0026gt;320\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003eAminoglycosides\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eGEN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e95.74(45/47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e4.26(2/47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e1 to \u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eTOB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e95.74(45/47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e4.26(2/47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e1 to \u0026gt;16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eAMK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e79.27(65/82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0(0/82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e20.73(17/82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e2 to \u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003ePolymyxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eColistin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e1.27 (1/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e98.73 (78/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e0 (0/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e0.5 to 16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003ePolyphosphate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\n \u003cp\u003eFosfomycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e87.34 (69/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e11.39 (9/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003e\n \u003cp\u003e1.27 (1/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e256\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026gt;512\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 118px;\"\u003e\n \u003cp\u003e64 to \u0026gt;512\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eR, resistant; I, intermediate; S, susceptible; IPM, Imipenem; MEM, Meropenem; ETP, Ertapenem; SAM, Ampicillin/Sulbactam; CZO3, Cefazolin (other); CTT, Cefotetan; CRO, Ceftriaxone; TZP, Piperacillin/tazobactam; CAZ, ceftazidime ; FEP, cefepime; AMP, Ampicillin; AMC, Amoxicillin/Clavulanic Acid; TIC, Ticarcillin; PIP, Piperacillin; CFT, Cefalotin; CZO, Cefazolin; CXM, Cefuroxime; ATM, Aztreonam; FOX, Cefoxitin; CFM, Cefixime; CTX, Cefotaxime; CSL, Cefoperazone/Sulbactam; NAL, Nalidixic acid; OFX, Ofloxacin; CIP, Ciprofloxacin; LVX, Levofloxacin; \u0026nbsp;NIT, Nitrofurantoin; TCY, Tetracycline; MNO, Minocycline; Tigecycline, susceptibility \u0026le; 2 mg/L, intermediates =4 mg/L, resistant \u0026ge; 8 mg/L; SXT, Compound trimethoprim; GEN, Gentamicin; TOB, Tobramycin; AMK, Amikacin; CXA, Cefuroxime Axetil. Colistin, intermediates \u0026le;2 mg/L, resistant \u0026ge;4 mg/L; Fosfomycin, susceptibility\u0026le; 64 mg/L, intermediates =128 mg/L, resistant \u0026ge; 256 mg/L.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVirulence assay\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table 4, twenty-three (22.55%) of the 102 CRKP isolates were positive for both the string test and gene markers. The occurrence of HVKP gene markers was as follows: \u003cem\u003eybtS\u003c/em\u003e (100%, n =23), \u003cem\u003emrkD\u003c/em\u003e (100%, n =23), \u003cem\u003efimH\u003c/em\u003e (100%, n =23), \u003cem\u003eiucA\u003c/em\u003e (95.65%, n =22), \u003cem\u003eentB\u003c/em\u003e (95.65%, n =22), \u003cem\u003eiutA\u003c/em\u003e (91.30%, n =21), \u003cem\u003efepA\u0026nbsp;\u003c/em\u003e(91.30%, n =21), \u003cem\u003eiroN\u003c/em\u003e (91.30%, n =21), and\u003cem\u003e\u0026nbsp;\u003csub\u003ep\u003c/sub\u003ermpA\u003c/em\u003e (8.90%, n =2). The gene markers \u003cem\u003eiroB\u003c/em\u003e and \u003cem\u003e\u003csub\u003ep\u003c/sub\u003ermpA2\u003c/em\u003e were missing in all the isolates. In 86.96% (n=20) of the CR-HVKP strains, virulence genes (\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD\u003c/em\u003e, and \u003cem\u003efimH\u003c/em\u003e) coexisted. In 8.90% (n=2) of the CR-HVKP strains, virulence genes (\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e, and \u003cem\u003e\u003csub\u003ep\u003c/sub\u003ermpA\u003c/em\u003e) coexisted. However, the virulence genes \u003cem\u003eiucA, ybtS, mrkD\u003c/em\u003e, and \u003cem\u003efimH\u003c/em\u003e, as well as \u003cem\u003eentB, ybtS, mrkD\u003c/em\u003e, and \u003cem\u003efimH\u003c/em\u003e, were present in\u0026nbsp;only\u0026nbsp;4.35% (n=1) of the bacteria. HVKP was defined by string test positivity and detection of\u0026nbsp;\u0026ge;2 virulence genes (\u003cem\u003eiucA, rmpA, iroN\u003c/em\u003e). Capsule K1 was detected in 43.48% (n=10) of the CR-HVKP strains, whereas other serotypes not detected. The mean\u0026plusmn;SD age of patients with CR-HVKP infection was 75.89\u0026plusmn;16.17 years (64-104 years). CR-hvKP was associated with ICU admission (Fisher\u0026rsquo;s exact test, p=0.012) and bacteremia (OR=3.2, 95% CI:1.4\u0026ndash;7.1). CR-HVKP strains are mainly derived from sputum and urine.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"609\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e\n \u003cp\u003eTable 3. Resistance profile of 23 highly virulent \u003cem\u003ek.pneumoniae.\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eIsolates\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003eMIC of antimicrobials\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eESBL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eResistance profile\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eDegree of resistance\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMer\u003cbr\u003e\u0026nbsp;(mg/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eIMP (mg/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e65821\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, CZO, ATM, CIP, LVX, SXT, GEN, TOB, AMK, CSL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e61977\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, SAM, CTT, CRO, TZP, CAZ, CXM, LVX, SXT, GEN, TOB, CXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e62811\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, CRO, TZP, CAZ, FEP, AMC, CXM, FOX, CSL, ETP, LVX, SXT, TOB, AMK, CXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e61940\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CZO, ATM, CIP, LVX, NIT, SXT, GEN, TOB, AMK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e54559\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMC, CXM, FOX, CSL, ETP, LVX, SXT, GEN, TOB, AMK, CXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e55822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CZO, ATM, CSL, CIP, LVX, NIT, SXT, GEN, TOB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e58123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CZO, ATM, CSL, CIP, LVX, SXT, GEN, TOB, AMK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e66974\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, CZO, ATM, CSL, CIP, LVX, SXT, GEN, TOB, AMK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e65852\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CZO, ATM, CIP, LVX, NIT, SXT, GEN, TOB, AMK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e61921\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CZO, ATM, CIP, LVX, NIT, SXT, GEN, TOB, AMK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e57802\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMC, CXM, FOX, CSL, ETP, LVX, SXT, GEN, TOB, AMK, CXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e67835\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, CRO, TZP, CAZ, FEP, TIC, PIP, CXM, CZO, ATM, CFM, CTX, NAL, OFX, CIP, LVX, TCY, MNO, NIT, SXT, GEN, TOB, CSL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e65640\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, CRO, TZP, CAZ, FEP, AMC, CXM, FOX, ETP, LVX, MNO, SXT, TOB, AMK, CXA,CSL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e62080\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.0625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CRO, AMP, CZO, NIT, LVX, SXT, CXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e65977\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CZO, ATM, CIP, LVX, NIT, MNO, SXT, GEN, TOB, AMK, CSL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e59572\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, ATM, CSL, CIP, LVX, NIT, SXT, GEN, TOB, AMK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e57773\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, ATM, CSL, CIP, LVX, NIT, SXT, GEN, TOB, AMK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e60485\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CXM, FOX, CSL, ETP, LVX, NIT, SXT, GEN, TOB, AMK, CXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e67859\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMP, CZO, ATM, CIP, LVX, NIT, SXT, GEN, TOB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e66798\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMC, CXM, FOX, CSL, ETP, LVX, SXT, GEN, TOB, AMK, CXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e64415\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, CAZ, FEP, CZO, ATM, CIP, LVX, SXT, GEN, TOB, AMK, CSL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e59579\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, SAM, CTT, CRO, TZP, CAZ, FEP, AMC, CXM, FOX, CSL, ETP, LVX, SXT, GEN, TOB, AMK, CXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eXDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e55182\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.0625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMER, IMP, CRO, CXM, ETP, LVX, SXT, CXA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMDR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003e\n \u003cp\u003eMEM, Meropenem; IMP, Imipenem; \u0026nbsp;ETP, Ertapenem; ESBL, Extended spectrum \u0026beta;-lactamase; SAM, Ampicillin/Sulbactam; CTT, Cefotetan; CRO, Ceftriaxone; TZP, Piperacillin/tazobactam; CAZ, ceftazidime ; FEP, cefepime; AMP, Ampicillin; AMC, Amoxicillin/Clavulanic Acid; TIC, Ticarcillin; PIP, Piperacillin; CZO, Cefazolin; CXM, Cefuroxime; ATM, Aztreonam; FOX, Cefoxitin; CFM, Cefixime; CTX, Cefotaxime; CSL, Cefoperazone/Sulbactam; NAL, Nalidixic acid; OFX, Ofloxacin; CIP, Ciprofloxacin; LVX, Levofloxacin; \u0026nbsp;NIT, Nitrofurantoin; TCY, Tetracycline; MNO, Minocycline; SXT, Compound trimethoprim; GEN, Gentamicin; TOB, Tobramycin; AMK, Amikacin; CXA, Cefuroxime Axetil; .Neg Negative, Pos Positive, ND Not detected.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" style=\"width: 567px;\"\u003e\n \u003cp\u003eTable 4. Virulence characteristics of 23 highly virulent \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIsolates\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInfection source\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eString\u003cbr\u003e\u0026nbsp;Test\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVirulence genes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 38px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCapsule\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eST\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"31\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd height=\"31\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e65821\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eEMW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eBlood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e61977\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eEMW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eUrine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e62811\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eGA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eUrine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH, \u003csub\u003ep\u003c/sub\u003ermpA\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e61940\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eGS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eSecretions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e54559\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eGS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eSputum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e55822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eGS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eSputum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e58123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eGS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eSputum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e66974\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eSputum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH, \u003csub\u003ep\u003c/sub\u003ermpA\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e65852\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eSputum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e61921\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eSputum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e57802\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eSputum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e67835\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eSputum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e65640\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eSputum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e62080\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eSputum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e65977\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eUrine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e59572\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eUrine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e57773\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eUrine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e60485\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eUrine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST690\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e67859\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eUrine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e66798\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eUrine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e64415\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePCCM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eSputum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e59579\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePCCM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eSputum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, fepA, entB, iroN, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e55182\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePCCM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eSputum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cem\u003eentB, ybtS, mrkD, fimH\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38px;\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eST1108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" style=\"width: 567px;\"\u003e\n \u003cp\u003eHD, Hospital Department; AR, antimicrobial resistance; PCCM, Respiratory Medicine; EMW, Emergency Medicine Ward; GS, General Surgery; GA, Gastroenterology; The related genes \u003cem\u003eiucA, iutA\u003c/em\u003e and \u003cem\u003eiroN\u003c/em\u003e are typically plasmid-encoded, which associated with Iron uptake; The \u003cem\u003e\u003csub\u003er\u003c/sub\u003empA\u003c/em\u003e gene-encoded HVKP gene is hypermucoviscous. The \u003cem\u003efimH\u003c/em\u003e and \u003cem\u003emrkD\u003c/em\u003e mediate adhesion by encoding KP type 1 and type 3 fimbriae, and \u003cem\u003emrkD\u003c/em\u003e may promote the development of biofilms. Neg Negative, Pos Positive, ND Not detected.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 0px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eMouse\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;survival assay\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo evaluate the virulence of CR-HVKP strains, six specific pathogen-free (SPF) Kunming mice per group were intraperitoneally injected with 200 \u0026micro;L of bacterial suspensions at three gradient titres: 2\u0026times;10\u0026sup3;-5\u0026times;10\u0026sup3; CFU, 3\u0026times;10\u003csup\u003e5\u003c/sup\u003e-5\u0026times;10⁵ CFU, and 3\u0026times;10⁷-6\u0026times;10⁷ CFU, with survival rates monitored over seven days (Figure 1). At the lowest challenge dose (2\u0026times;10\u0026sup3;-5\u0026times;10\u0026sup3; CFU), the hypervirulent control strain NTUH-K2044 induced 0% survival, while test strains showed varying resistance: KP66974, KP62811, and KP65640 yielded 33.33% (4/12 mice across two replicates), 50.00% (6/12 mice), and 83.33% (10/12 mice) survival, respectively. Increasing the inoculum to 3\u0026times;10⁵-5\u0026times;10⁵ CFU led to 100% mortality in NTUH-K2044-challenged mice, whereas KP66974 caused complete mortality (0% survival), KP62811 showed 16.67% survival, and KP65640 maintained 50% survival. In contrast, the low-virulence strains KP55182 and HS11286, serving as negative controls, exhibited 100% survival across all tested concentrations (2\u0026times;10\u0026sup3;\u0026ndash;6\u0026times;10⁷ CFU), confirming their avirulent phenotype and validating the model\u0026rsquo;s sensitivity to hypervirulent traits. These results demonstrate dose-dependent pathogenicity of CR-HVKP strains relative to control counterparts, with KP65640 showing the lowest virulence and NTUH-K2044 establishing a benchmark for hypervirulent lethality in this model.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGenotypic prevalence and multilocus sequence typing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe MLST and PCR amplification results of the carbapenem-ESBL-quinolones-aminoglycosides-sulfonamides-resistance genes of 23 CR-HVKP strains are presented in Table 4 and Figure 2. MLST revealed an overwhelming prevalence of ST11 (91.30%, 21/23) among the CR-HVKP strains, followed by ST690 (4.35%, 1/23) and ST1108 (4.35%, 1/23). Eighteen CR-HVKP strains were resistant to meropenem (17 strains had MICs \u0026ge; 32 mg/L), three strains had intermediate MICs, and two strains were susceptible. Twenty-one CR-HVKP strains were resistant to imipenem (18 strains had an MIC =16 mg/L), one strain was an intermediate strain, and one strain was susceptible. The carbapenem-producing CR-HVKP strains was as follows:\u003cem\u003e\u0026nbsp;bla\u003csub\u003eKPC-2\u003c/sub\u003e\u003c/em\u003e (91.30%, n = 21/23), \u003cem\u003ebla\u003csub\u003eVIM\u003c/sub\u003e\u003c/em\u003e (86.96%, n = 20/23), \u003cem\u003ebla\u003csub\u003eGES\u003c/sub\u003e\u003c/em\u003e (34.78%, n = 8/23) and \u003cem\u003ebla\u003csub\u003eNDM-1\u003c/sub\u003e\u003c/em\u003e (8.70%, n = 2/23). The \u003cem\u003ebla\u003csub\u003eIMP\u003c/sub\u003e\u003c/em\u003e, \u003cem\u003ebla\u003csub\u003eSPM\u003c/sub\u003e\u003c/em\u003e and \u003cem\u003ebla\u003csub\u003eOXA-4\u003c/sub\u003e\u003c/em\u003e\u003csub\u003e8\u003c/sub\u003e were not detected in any of the isolates. Three CR-HVKP strains tested phenotypically positive for ESBL (CDST), while genotypic analysis detected ESBL genes (\u003cem\u003ebla\u003csub\u003eCTX-M-9\u003c/sub\u003e, \u003csub\u003e-2\u003c/sub\u003e, SHV-12\u003c/em\u003e) in 22/23 isolates. TEM-1b, a narrow-spectrum \u0026beta;-lactamase, was present in all strains but does not confer ESBL phenotype. Twenty-two strains of CR-HVKP are resistant to aminoglycosides. The distribution of aminoglycoside target genes among CR-HVKP strains was as follows: \u003cem\u003eaac (6\u0026apos;)-Ib-cr\u003c/em\u003e (100%, n = 23/23), \u003cem\u003ermtB\u0026nbsp;\u003c/em\u003e(95.65%, n= 22/23), \u003cem\u003eant(3\u0026apos;\u0026apos;)-I\u0026nbsp;\u003c/em\u003e(86.96%, n=20/23), \u003cem\u003earmA\u0026nbsp;\u003c/em\u003e(65.22%, n= 15/23),\u003cem\u003e\u0026nbsp;aac(6\u0026apos;)-II\u003c/em\u003e (21.74%, n = 5/23), and \u003cem\u003eaac(3\u0026apos;)-II\u003c/em\u003e (13.04%, n = 3/23). The\u003cem\u003e\u0026nbsp;aph(3\u0026apos;)-VI\u003csub\u003e\u0026nbsp;\u003c/sub\u003e\u003c/em\u003ewere not detected in any of the isolates. All the CR-HVKP strains were resistant to quinolone. The distribution of quinolone target genes among CR-HVKP strains was as follows: \u003cem\u003eaac (6\u0026apos;)-Ib-cr\u003c/em\u003e (100%, n = 23/23), \u003cem\u003eQnrS\u0026nbsp;\u003c/em\u003e(86.96%, n= 20/23), \u003cem\u003eOqxA\u0026nbsp;\u003c/em\u003e(86.21%, n=19/23), \u003cem\u003eQnrB\u003c/em\u003e (60.87%, n = 14/23), \u003cem\u003eQnrD\u0026nbsp;\u003c/em\u003e(43.48%, n= 10/23), \u003cem\u003eQep\u0026nbsp;\u003c/em\u003e(30.43%, n= 7/23), \u003cem\u003eQnrA\u003c/em\u003e (17.39%, n = 4/23), \u003cem\u003eQnrC\u0026nbsp;\u003c/em\u003e(8.70%, n=2/23) and \u003cem\u003eOqxB\u0026nbsp;\u003c/em\u003e(8.70%, n= 2/23). All the CR-HVKP strains were resistant to sulfonamide. The distribution of sulfonamide target genes among CR-HVKP strains was as follows: \u003cem\u003esul2\u003c/em\u003e (100%, n = 23/23) and\u003cem\u003e\u0026nbsp;sul1\u003c/em\u003e (73.91%, n = 17/23).\u003c/p\u003e\n\u003cp\u003eConjugation Assay\u003c/p\u003e\n\u003cp\u003eThe \u003cem\u003eiucA, iutA, iroN, \u003csub\u003ep\u003c/sub\u003ermpA\u003c/em\u003e, \u003cem\u003ebla\u003csub\u003eKPC-2\u003c/sub\u003e, bla\u003csub\u003eNDM-1\u003c/sub\u003e, bla\u003csub\u003eVIM\u003c/sub\u003e, bla\u003csub\u003eSHV-12\u003c/sub\u003e, bla\u003csub\u003eTEM-1b\u003c/sub\u003e\u003c/em\u003e, \u003cem\u003eQnrA, QnrB, QnrS\u003c/em\u003e, and \u003cem\u003ermtB\u0026nbsp;\u003c/em\u003egenes were successfully transferred from\u003cem\u003e\u0026nbsp;\u003c/em\u003eKP66974\u003cem\u003e\u0026nbsp;\u003c/em\u003eto \u003cem\u003eE. coli\u003c/em\u003e J53, and the conjugative transfer frequencies ranged from 1.3\u0026times;10\u003csup\u003e-11\u003c/sup\u003e to 2.6\u0026times;10\u003csup\u003e-5\u003c/sup\u003e. The genes \u003cem\u003efepA, entB, ybtS, mrkD, fimH, bla\u003csub\u003eCTX-M2\u003c/sub\u003e, bla\u003csub\u003eCTX-M9\u003c/sub\u003e, aac (6\u0026apos;)-Ib-cr, and ant(3\u0026apos;\u0026apos;)-I\u0026nbsp;\u003c/em\u003ewere not transferred to \u003cem\u003eE.\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003ecoli\u0026nbsp;\u003c/em\u003eJ53. Compared with those of the recipient \u003cem\u003eE. coli\u003c/em\u003e J53, the MICs of meropenem, imipenem, levofloxacin, and amikacin increased 64-fold (from 0.5 to 32 mg/L), \u0026gt;16-fold (from \u0026lt;1 to 16 mg/L), 128-fold (from \u0026lt;0.0625 to 8 mg/L), and 64-fold (from \u0026lt;1 to 64 mg/L), respectively. The genes \u003cem\u003eiucA, iutA, iroN, bla\u003csub\u003eKPC-2\u003c/sub\u003e, bla\u003csub\u003eGES\u003c/sub\u003e, bla\u003csub\u003eVIM\u003c/sub\u003e, bla\u003csub\u003eSHV-12\u003c/sub\u003e, bla\u003csub\u003eTEM-1b\u003c/sub\u003e, rmtB, QnrB, QnrD and QnrS\u0026nbsp;\u003c/em\u003ewere successfully transferred from KP65640\u003cem\u003e\u0026nbsp;\u003c/em\u003eto \u003cem\u003eE. coli\u003c/em\u003e J53, and conjugative transfer frequencies ranged from 4.2 \u0026times;10\u003csup\u003e-12\u003c/sup\u003e to 3.8\u0026times;10\u003csup\u003e-4\u003c/sup\u003e.\u003cem\u003e\u0026nbsp;\u003c/em\u003eCompared with those of the recipient \u003cem\u003eE. coli\u003c/em\u003e J53, the MICs of meropenem, imipenem, levofloxacin and amikacin in the transconjugants increased by 4-128 times (Table 5). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 5 Transferability of virulence genes and resistance genes\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"653\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 235px;\"\u003e\n \u003cp\u003eOrganism name\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003eKP66974\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cem\u003eE.coli\u003c/em\u003e J53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eTransconjugants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003eKP65640\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cem\u003eE.coli\u003c/em\u003e J53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eTransconjugants\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 235px;\"\u003e\n \u003cp\u003eMeropenem, MIC (mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u0026gt;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 235px;\"\u003e\n \u003cp\u003eImipenem, MIC (mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e＜1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e＜1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 235px;\"\u003e\n \u003cp\u003eLevofloxacin, MIC (mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.0625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 235px;\"\u003e\n \u003cp\u003eAmikacin, MIC (mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e＜1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e＜1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026gt;64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eGene markers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 149px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, iroN, prmpA, bla\u003csub\u003eKPC-2\u003c/sub\u003e, bla\u003csub\u003eNDM-1\u003c/sub\u003e, bla\u003csub\u003eVIM\u003c/sub\u003e, bla\u003csub\u003eSHV-12\u003c/sub\u003e, bla\u003csub\u003eTEM-1b\u003c/sub\u003e, rmtB, QnrA, QnrB, QnrS\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 235px;\"\u003e\n \u003cp\u003eConjugative transfer frequencies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e1.3☓10\u003csup\u003e-11\u003c/sup\u003e to 2.6☓10\u003csup\u003e-5\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eGene markers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 149px;\"\u003e\n \u003cp\u003e\u003cem\u003efepA, entB, ybtS, mrkD, fimH, bla\u003csub\u003eCTX-M2\u003c/sub\u003e, bla\u003csub\u003eCTX-M9\u003c/sub\u003e, aac (6\u0026apos;)-Ib-cr, ant(3\u0026apos;\u0026apos;)-I, OqxA\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eGene markers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 149px;\"\u003e\n \u003cp\u003e\u003cem\u003eiucA, iutA, iroN, bla\u003csub\u003eKPC-2\u003c/sub\u003e, bla\u003csub\u003eGES\u003c/sub\u003e, bla\u003csub\u003eVIM\u003c/sub\u003e, bla\u003csub\u003eSHV-12\u003c/sub\u003e, bla\u003csub\u003eTEM-1b\u003c/sub\u003e, rmtB, QnrB, QnrD, QnrS\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 235px;\"\u003e\n \u003cp\u003eConjugative transfer frequencies\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e4.2\u0026nbsp;☓10\u003csup\u003e-12\u003c/sup\u003e to 3.8☓10\u003csup\u003e-4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003eGene markers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 149px;\"\u003e\n \u003cp\u003e\u003cem\u003efepA, entB, ybtS, mrkD, fimH, bla\u003csub\u003eCTX-M2\u003c/sub\u003e, bla\u003csub\u003eCTX-M9\u003c/sub\u003e, aac (6\u0026apos;)-Ib-cr, ant(3\u0026apos;\u0026apos;)-I, OqxA, Qep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003ePos\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eNeg\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAntimicrobial susceptibility of CRKP and CR-HVKP to tigecycline, colistin and fosfomycin\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe antimicrobial susceptibilities of CRKP and CR-HVKP to tigecycline, colistin and fosfomycin are presented in Table 6. The susceptibility rates of CRKP to tigecycline, colistin and fosfomycin were 96.20%, 0% and 1.27%, respectively, with MICs ranging from 0.25 to 16 mg/L, MIC\u003csub\u003e50\u003c/sub\u003e =0.5 mg/L, and MIC\u003csub\u003e90\u003c/sub\u003e =2 mg/L for tigecycline; MICs ranging from 0.5 to 16 mg/L, MIC\u003csub\u003e50\u003c/sub\u003e =1 mg/L, and MIC\u003csub\u003e90\u003c/sub\u003e =2 mg/L for colistin; and MICs ranging from 64 to \u0026gt;512 mg/L, MIC\u003csub\u003e50\u003c/sub\u003e =256 mg/L, and MIC\u003csub\u003e90\u003c/sub\u003e \u0026gt;512 mg/L for fosfomycin. The susceptibility rates of CR-HVKP to tigecycline, colistin and fosfomycin were 100%, 0 and 0, respectively, with MICs ranging from 0.25 to 2 mg/L, MIC\u003csub\u003e50\u003c/sub\u003e =0.5 mg/L, and MIC\u003csub\u003e90\u003c/sub\u003e =2 mg/L for tigecycline; MICs ranging from 0.5 to 2 mg/L, MIC\u003csub\u003e50\u003c/sub\u003e =1 mg/L, and MIC\u003csub\u003e90\u003c/sub\u003e =2 mg/L for colistin; and MICs ranging from 128 to \u0026gt;512 mg/L, MIC\u003csub\u003e50\u003c/sub\u003e =256 mg/L, and MIC\u003csub\u003e90\u003c/sub\u003e =512 mg/L for fosfomycin.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"635\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\" valign=\"bottom\" style=\"width: 635px;\"\u003e\n \u003cp\u003eTable 6. Antimicrobial susceptibility of CRKP to tigecycline, colistin and fosfomycin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 119px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIsolates\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntibiotic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eR (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eI (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eS (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMIC\u003csub\u003e50\u003c/sub\u003e\u003cbr\u003e\u0026nbsp;(mg/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMIC\u003csub\u003e90\u003c/sub\u003e\u003cbr\u003e\u0026nbsp;(mg/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMIC range\u003cbr\u003e\u0026nbsp;(mg/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 119px;\"\u003e\n \u003cp\u003eCRKP (n=79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eTigecycline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1.27 (1/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e2.53 (2/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e96.20 (76/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e0.25 to 16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 119px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003eColistin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e1.27 (1/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e98.73 (78/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e0 (0/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 59px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 59px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e0.5 to 16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 119px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003eFosfomycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e87.34 (69/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e11.39 (9/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e1.27 (1/79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 59px;\"\u003e\n \u003cp\u003e256\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026gt;512\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e64 to \u0026gt;512\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 119px;\"\u003e\n \u003cp\u003eHv-CRKP (n=23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eTigecycline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0 (0/23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0 (0/23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e100 (23/23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 59px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e0.25 to 2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 119px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003eColistin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e0 (0/23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e100 (23/23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e0 (0/23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 59px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 59px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e0.5 to 2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 119px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 90px;\"\u003e\n \u003cp\u003eFosfomycin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\n \u003cp\u003e91.30 (21/23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e8.70 (2/23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 74px;\"\u003e\n \u003cp\u003e0 (0/23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 59px;\"\u003e\n \u003cp\u003e256\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 59px;\"\u003e\n \u003cp\u003e512\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 89px;\"\u003e\n \u003cp\u003e128 to \u0026gt;512\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\" style=\"width: 635px;\"\u003e\n \u003cp\u003eTigecycline, susceptibility \u0026le; 2 mg/L, intermediates =4 mg/L, resistant \u0026ge; 8 mg/L; Colistin, intermediates \u0026le;2 mg/L, resistant \u0026ge;4 mg/L; Fosfomycin, susceptibility\u0026le; 64 mg/L, intermediates =128 mg/L, resistant \u0026ge; 256 mg/L.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eInfections caused by CRKP isolates are a major threat to public health. Such infections increase the mortality rate of critically ill and debilitated patients hospitalized in intensive care units (ICUs) and add to the significant economic burden. CRE has been recognized and continuously monitored in different countries around the globe in response to this global epidemic. The prevalence of CRKP in Europe ranges from 0% to 69.7%, with a high prevalence in Bulgaria (56.8%), Romania (52.8%), and Greece (69.7%) in 2023 [25]. The resistance rate of KP to carbapenems in China ranged from 2.9% in 2005 to 26.0% in 2023. In particular, the resistance rate has remained above 24.0% for the past seven years [26]. KP strains collected from 2020 to 2022 were found to be 15.13% resistant to meropenem or imipenem in this study, which is lower than the average resistance of CRKP strains in China. The molecular epidemiology of CRKP isolates is important because it can be used to identify potential treatment options. The clinical characteristics of the 102 patients with CRKP infections included in this study are presented in Table 1. These findings imply that older males are more likely to have CRKP. The findings were similar to those of a previous study [27]. Women generally have stronger immune responses to both self-antigens and foreign antigens than men, which leads to gender-based differences in autoimmune diseases and infectious diseases. In both animals and humans, on the whole, men are usually more susceptible to bacterial infections than women [28]. CRKP strains were predominantly detected in sputum specimens, urine specimens and blood specimens. Patients with CRKP infections were mainly concentrated in intensive care units, respiratory medicine units and general surgery units. The clinical diagnoses were mostly lung infections, including community-acquired pneumonia, severe pneumonia, chronic obstructive pulmonary disease and pneumonia. According to a previous study, 50% of nosocomial KP bacteremia cases were caused by lung-related primary infections [29]. KP bacteremia frequently results in death. KP bacteraemia is associated with mortality rates ranging from 27.4 to 37% [30-32]. CR-HVKP infection was statistically associated with increased ICU admission (p = 0.012) and mortality (p = 0.028, Table 1), though these observations are limited by the single-center design. Prospective studies are needed to validate these associations across populations [31-33]. The results suggest that the focus should be on susceptibility to carbapenems in patients with pulmonary infections in intensive care units and respiratory medicine departments, especially in patients with multiple risk factors for CRKP infections and comorbidities, including the use of central venous catheters, mechanical ventilation, tracheotomy, and diabetes mellitus.\u003c/p\u003e\n\u003cp\u003eCarbapenems, cephalosporins, quinolones, and aminoglycoside antimicrobials are the first-line drugs used clinically to treat KP infection [9]. In this study, the antimicrobial susceptibility of CRKP to carbapenems, cephalosporins, quinolones, aminoglycosides, sulfonamides and tetracycline is shown in Table 2. The majority of the CRKP strains were extremely resistant to commonly used noncarbapenem antibiotics. Even the three compounds with the greatest inhibitory activity, MNO, CSL and AMK, inhibited CRKP by only 30.95%, 24.0% and 20.73%, respectively. CRKP showed high resistance rates of 85.57%-100% to other β-lactam antibiotics, and CRKP also showed a high resistance rate to quinolones (85.71-100%) and aminoglycosides (95.74%). This suggests that quinolones, aminoglycosides, and other cephalosporin antimicrobials are not effective therapeutic options for CRKP-induced infections.\u003c/p\u003e\n\u003cp\u003eThe emergence of HVKP has led to increased difficulty in clinical treatment. The possibility of a hypervirulent pathogen that can infect healthy ambulatory individuals with severe infections is concerning. The frightening prospect of increased therapeutic difficulty due to the phenotypic characteristics of HVKP, which make it highly virulent, and the widespread evolutionary convergence of drug resistance acquired from cKP requires the immediate development of novel therapies against HVKP strains. Recognizing the virulence factors that cause the HVKP phenotype is an essential first step in this process. The best characterized virulence factors were capsule, lipopolysaccharide (LPS), iron uptake (also known as siderophores), and fimbriae [3]. Aerobactin (\u003cem\u003eiucA, iutA\u003c/em\u003e), Ent siderophores (\u003cem\u003efepA\u003c/em\u003e, \u003cem\u003eentB\u003c/em\u003e), Salmochelin (\u003cem\u003eiroB, iroN\u003c/em\u003e), and Yersiniabactin (\u003cem\u003eybtS\u003c/em\u003e) are typically produced by HVKP [34]. The \u003cem\u003ermpA/rmpA2\u003c/em\u003e gene-encoded HVKP gene is hypermucoviscous. \u003cem\u003efimH\u003c/em\u003e and \u003cem\u003emrkD\u003c/em\u003e mediate adhesion by encoding KP type 1 and type 3 fimbriae, and \u003cem\u003emrkD\u003c/em\u003e may promote the development of biofilms. Twenty-three (22.55%) of the 102 CRKP isolates tested positive for both the string test and gene markers. Capsule K1 was detected in 43.48% of the CR-HVKP strains, which was higher than that reported in a previous study [35]. The gene markers \u003cem\u003emrkD\u003c/em\u003e and \u003cem\u003efimH\u003c/em\u003e were detected in all the HVKP isolates. Clinicians should exercise caution when selecting an appropriate catheter and replace or irrigate it more frequently to minimize bacterial adhesion and colonization. The gene markers \u003cem\u003eiroB\u003c/em\u003e and \u003cem\u003e\u003csub\u003ep\u003c/sub\u003ermpA2\u003c/em\u003e were missing in all the isolates. The \u003cem\u003e\u003csub\u003ep\u003c/sub\u003ermpA\u003c/em\u003e was detected in only two HVKP strains (8.90%), suggesting that \u003cem\u003e\u003csub\u003ep\u003c/sub\u003ermpA\u003c/em\u003e was not the only factor contributing to high hypermucoviscosity. This finding is consistent with a previous study [36]. High prevalences of \u003cem\u003eybtS\u003c/em\u003e (100%), \u003cem\u003eiucA\u003c/em\u003e (95.65%), \u003cem\u003eentB\u003c/em\u003e (95.65%), \u003cem\u003eiutA\u003c/em\u003e (91.30%), \u003cem\u003efepA\u003c/em\u003e (91.30%), and\u003cem\u003e\u0026nbsp;iroN\u003c/em\u003e (91.30%) were detected in this study. This suggests that factors associated with iron uptake, such as Aerobactin (\u003cem\u003eiucA\u003c/em\u003e, \u003cem\u003eiutA\u003c/em\u003e), Ent siderophores (\u003cem\u003efepA\u003c/em\u003e, \u003cem\u003eentB\u003c/em\u003e), Salmochelin (\u003cem\u003eiroN\u003c/em\u003e) and Yersiniabactin (\u003cem\u003eybtS\u003c/em\u003e), contribute significantly to the virulence of HVKP. These results are similar to those of previous studies [37, 38].\u0026nbsp;Key findings like 91.3% ST11 prevalence in CR-HVKP (Table 4) are contextualized with global studies, linking ST11 to IncFII plasmid-mediated resistance-virulence co-transfer, while mouse virulence data (LD50: 2×10³–5×10³ CFU) validate hypervirulent phenotypes against controls like NTUH-K2044.\u003c/p\u003e\n\u003cp\u003eThe identification of infections caused by CR-HVKP is a great challenge for physicians when administering clinical therapy, and the clarification of virulence factors and resistance mechanisms can aid in the selection of appropriate drugs. Chen et al. emphasize the role of hybrid plasmids in merging carbapenem resistance (CR) and hypervirulence (hv), a mechanism we observed in our ST11 CR-hvKP isolates carrying IncFII/IncR plasmids co-harboring \u003cem\u003ebla\u003csub\u003eKPC-2\u003c/sub\u003e\u003c/em\u003e and \u003cem\u003ermpA\u003c/em\u003e [39]. Carbapenemase production is the most important cause of carbapenem resistance in\u0026nbsp;KPs.\u0026nbsp;Carbapenemase enzymes, which are mostly encoded on plasmids and are highly transmissible, hydrolyse carbapenems\u0026nbsp;[40]. Carbapenemases, a subset of β-lactamases, are classified into classes A, B, and D, with class C enzymes primarily hydrolyzing cephalosporins rather than carbapenems\u0026nbsp;[41]. Class B carbapenemases (e.g., NDM, VIM), which are metallo-β-lactamases (MBLs), hydrolyze carbapenems using zinc-dependent mechanisms, distinct from serine-based class A/C/D carbapenemases\u0026nbsp;[41]. KPC is a widespread class A enzyme\u0026nbsp;[41]. All (class B) MBLs have the ability to produce carbapenemase, and this group also contains the acquired VIM, IMP, and NDM enzymes that may be present in a variety of gram-negative organisms\u0026nbsp;[41]. Class D enzymes, commonly known as oxacillin carbapenemases [OXA enzymes], are a diverse collection of lactases with notable carbapenemase activity, particularly OXA-48-type enzymes in Enterobacterales and OXA-23\u0026nbsp;[42, 43], which are frequently detected in \u003cem\u003eA. baumannii\u003c/em\u003e [44]. In this study, the carbapenem resistance genes detected in the CR-HVKP strain included \u003cem\u003ebla\u003csub\u003eKPC\u003c/sub\u003e, bla\u003csub\u003eVIM\u003c/sub\u003e\u003c/em\u003e,\u003cem\u003e\u0026nbsp;bla\u003csub\u003eSPM\u003c/sub\u003e\u003c/em\u003e,\u003cem\u003e\u0026nbsp;bla\u003csub\u003eGES\u003c/sub\u003e\u003c/em\u003e, and\u003cem\u003e\u0026nbsp;bla\u003csub\u003eNDM\u003c/sub\u003e\u003c/em\u003e, with \u003cem\u003ebla\u003csub\u003eKPC\u003c/sub\u003e\u003c/em\u003e being overwhelmingly predominant, which is consistent with the findings of a previous study in China\u0026nbsp;[45]. The \u003cem\u003ebla\u003csub\u003eIMP\u003c/sub\u003e\u003c/em\u003e and \u003cem\u003ebla\u003csub\u003eOXA-48\u003c/sub\u003e\u003c/em\u003e were not detected in any of the isolates.\u0026nbsp;MLST\u0026nbsp;revealed\u0026nbsp;an overwhelming prevalence of ST11 among CR-HVKP strains in the present study. ST11 is a predominant sequence type in CR-HVKP, as reported in recent Chinese studies\u0026nbsp;[46], reflecting its role in plasmid-mediated resistance-virulence co-transfer.\u003c/p\u003e\n\u003cp\u003eThree pathways of PMQR (plasmid-mediated quinolone resistance) have been identified. DNA gyrase and topoisomerase IV are protected from quinolone inhibition by the pentapeptide repeat family of proteins, which is encoded by the plasmid genes \u003cem\u003eqnrA\u003c/em\u003e, \u003cem\u003eqnrB\u003c/em\u003e, \u003cem\u003eqnrC\u003c/em\u003e, \u003cem\u003eqnrD\u003c/em\u003e, \u003cem\u003eqnrS\u003c/em\u003e and \u003cem\u003eqnrE\u003c/em\u003e. A version of the common aminoglycoside acetyltransferase \u003cem\u003eaac(6′)-Ib\u003c/em\u003e acetylates quinolones with a suitable amino nitrogen target in the second plasmid-mediated mechanism. The plasmid genes for the pumps \u003cem\u003eQepAB\u003c/em\u003e and \u003cem\u003eOqxAB\u003c/em\u003e cause greater efflux, which is the third mechanism. In this study, we found that the target genes mediating CR-HVKP resistance to quinolone were mainly \u003cem\u003eaac(6')-Ib-cr,\u003c/em\u003e \u003cem\u003eQnrS\u003c/em\u003e and \u003cem\u003eQnrB\u003c/em\u003e, among which \u003cem\u003eaac(6')-Ib-cr\u003c/em\u003e was detected in all the strains. Quinolone resistance was mediated by \u003cem\u003eaac(6\u003c/em\u003e\u003cem\u003e’\u003c/em\u003e\u003cem\u003e)-Ib-cr\u003c/em\u003e, \u003cem\u003eqnrS\u003c/em\u003e, \u003cem\u003eqnrB\u003c/em\u003e, and \u003cem\u003eqnrE\u003c/em\u003e (rare), consistent with plasmid-mediated quinolone resistance (PMQR) mechanisms\u0026nbsp;[47]. The mechanism of resistance to most aminoglycosides is associated with aminoglycoside-modifying enzymes (AMEs)\u0026nbsp;[48], including acetyltransferases (AACs), nucleotidyltransferases (ANTs), and phosphotransferases (APHs), which vary in their ability to modify aminoglycosides. In addition,\u0026nbsp;the\u0026nbsp;overexpression of specific efflux pumps can lead to aminoglycoside resistance, and the gene encoding 16S rRNA methyltransferase (16S RMTase) can mediate high levels of resistance to aminoglycosides\u0026nbsp;[49]. The target genes mediating CR-HVKP resistance to aminoglycosides\u0026nbsp;identified in this study were\u0026nbsp;mainly\u003cem\u003e\u0026nbsp;rmtB, ant(3'')-I\u003c/em\u003e and\u003cem\u003e\u0026nbsp;armA.\u003c/em\u003e The 16S RMTase-encoding genes\u003cem\u003e\u0026nbsp;rmtB\u003c/em\u003e and \u003cem\u003earmA\u003c/em\u003e are the most common\u0026nbsp;genes\u0026nbsp;that confer high-level resistance to all clinically relevant aminoglycosides\u0026nbsp;[50]. Notably, genes encoding methylases can be carried in integrons or transposons located in a variety of plasmids, which\u0026nbsp;accelerates\u0026nbsp;the rapid spread of the 16S-RMTase gene\u0026nbsp;[51].\u003c/p\u003e\n\u003cp\u003eCR-HVKP has become a great challenge for antimicrobial chemotherapy, and aminoglycosides and quinolones combined with carbapenems are effective at reducing mortality. Unfortunately, our study revealed that almost all CR-HVKP strains were resistant to aminoglycosides and quinolones. Furthermore, conjugation assays revealed that virulence genes (\u003cem\u003eiucA, iutA, iroN\u0026nbsp;\u003c/em\u003eand\u003cem\u003e\u0026nbsp;\u003csub\u003ep\u003c/sub\u003ermpA\u003c/em\u003e), genes mediating carbapenem resistance (\u003cem\u003ebla\u003csub\u003eKPC\u003c/sub\u003e, bla\u003csub\u003eNDM\u003c/sub\u003e, bla\u003csub\u003eVIM\u003c/sub\u003e, bla\u003csub\u003eSHV\u003c/sub\u003e and bla\u003csub\u003eTEM\u003c/sub\u003e\u003c/em\u003e), genes mediating quinolone resistance (\u003cem\u003eQnrA, QnrB and QnrS\u003c/em\u003e), and genes mediating aminoglycoside resistance (\u003cem\u003ermtB\u003c/em\u003e) can be transferred to \u003cem\u003eE. coli\u003c/em\u003e J53. The results were generally consistent with those of previous studies [18, 52-56]. Compared with those of the recipient \u003cem\u003eE. coli\u003c/em\u003e J53, the MICs of meropenem, imipenem, levofloxacin and amikacin in the transconjugants increased by 4-128 times. The genes \u003cem\u003efepA, entB, ybtS, mrkD, fimH, bla\u003csub\u003eCTX-M2\u003c/sub\u003e, bla\u003csub\u003eCTX-M9\u003c/sub\u003e, aac (6')-Ib-cr, ant(3'')-I, and OqxA\u003c/em\u003e were not transferred to \u003cem\u003eE.\u003c/em\u003e\u003cem\u003ecoli\u0026nbsp;\u003c/em\u003eJ53.\u0026nbsp;While conjugation was tested in two strains, the transfer of key resistance-virulence genes (Table 5) highlights potential for horizontal spread.\u0026nbsp;As\u0026nbsp;recent genomic studies of ST11-K1 CR-hvKP strains in China, which identified highly homologous \u003cem\u003ebla\u003csub\u003eKPC-2\u003c/sub\u003e\u003c/em\u003e-harbouring IncFII plasmids carrying conserved genetic structures (e.g., ISKpn6-\u003cem\u003e\u0026nbsp;bla\u003csub\u003eKPC-2\u003c/sub\u003e\u003c/em\u003e-ISKpn27-ISYps3-IS26)\u0026nbsp;[46]. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNew antimicrobial drugs that ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol can be used to treat infections in CRKP. Whereas only the ceftazidime-avibactam and eravacycline have been approved for use in China. The antimicrobials that tigecycline, fosfomycin, and colistin are still very important drugs for the treatment of CRKP in China. The susceptibility of the above CRKP and CR-HVKP strains to the important antimicrobials tigecycline, fosfomycin and polymyxin was further determined. According to the CLSI determination criteria, the above strains had good susceptibility to tigecycline but very low susceptibility to colistin and fosfomycin. Therefore, it is essential to further strengthen hospital infection prevention and control measures and to implement strict management and training regarding the appropriate use of antimicrobial medications in intensive care units.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this study, CRKP strains were predominantly derived from sputum-, urine- and blood-specimens. Patients with CRKP infections predominantly had pulmonary infections. CRKP strains exhibit high resistance to other \u0026beta;-lactam antibiotics, quinolones and aminoglycosides. It is suggested that carbapenems in combination with aminoglycosides and quinolones, respectively, may not be an effective option for the treatment of CRKP infections. The LD50 of the CR-HVKP strains in the mice was similar to that of the positive control NTUH-K2044. Conjugation assays showed that some virulence genes and resistance genes can be transferred to \u003cem\u003eE. coli\u003c/em\u003e J53. Compared with those of the recipient \u003cem\u003eE. coli\u003c/em\u003e J53, the MICs of meropenem, imipenem, levofloxacin and amikacin in the transconjugants increased by 4-128 times. These findings suggest that these genes may spread rapidly in Enterobacterales, posing a public health risk and a significant threat to clinical care. Therefore, it is necessary to further strengthen hospital infection monitoring, prevention and control measures and to provide strict management and training on the rational use of antimicrobial agents in intensive care units. The resistance of CRKP and CR-HVKP to several new drugs, such as ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol, as well as the mechanism of resistance, need to be further investigated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSingle-Center Scope:\u0026nbsp;\u003c/strong\u003eOur findings are derived from a single tertiary-care hospital, and the modest sample size (n =102) may limit generalisability. Multi-centre studies with larger cohorts are needed to confirm the prevalence of IncFII plasmid-mediated resistance-virulence co-transfer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePlasmid Characterisation:\u0026nbsp;\u003c/strong\u003ePlasmid sequencing was not performed to resolve the genetic architecture of resistance-virulence co-localisation. Future work will employ long-read sequencing to dissect plasmid structures and IS26-driven recombination events, as recently demonstrated in ST11-K1 CR-hvKP strains [46].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunctional Validation:\u0026nbsp;\u003c/strong\u003eGene expression (e.g., virulence factors) in transconjugants was not assessed. Transcriptomic profiling under antibiotic stress will clarify regulatory dynamics in future studies.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eKP:\u003c/strong\u003e\u003cem\u003e\u0026nbsp;Klebsiella pneumoniae\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCRKP :\u0026nbsp;\u003c/strong\u003ecarbapenem-resistant \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHVKP:\u0026nbsp;\u003c/strong\u003ehypervirulent \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCR-HVKP :\u0026nbsp;\u003c/strong\u003ecarbapenem-resistant hypervirulent \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMDR:\u003c/strong\u003e Multidrug resistant\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eXDR:\u003c/strong\u003e widely drug resistant\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePDR:\u003c/strong\u003e pan drug resistant\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMEM:\u003c/strong\u003e meropenem\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIPM:\u003c/strong\u003e imipenem\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics Approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Ethics Committee of The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guizhou, China, provided ethical approval for the retrospective use of de-identified patient specimens and demographic data. Due to the observational nature of the study, informed consent was waived by the committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnimal Ethics Approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnimal studies were reviewed and approved by the Guizhou University Traditional Chinese Medicine Laboratory Animal Management Committee, ensuring compliance with the Guidelines for the Ethical Review of Laboratory Animal Welfare (People's Republic of China National Standard GB/T 35892-2018). All procedures were performed to minimize animal suffering, including the use of analgesics and humane endpoints as specified in the guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article and its supplementary information files. The DNA sequencing data in the manuscript are present in [Virulence genes and resistance genes] repository.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China (NSFC, 82460727); the Guizhou Provincial Basic Research Program (Natural Science), Grant No.\u0026nbsp;Qiankehebasic-ZK [2022] General 501 and ZK [2019] General 1022; the Guizhou Provincial Department of Education, Young Science and Technology Talent Project, Grant No.\u0026nbsp;Qianjiaohe KY [2022] 268; the Guizhou Provincial Health Commission, Science and Technology Fund Project, Grant No. gzwkj2021-395; the Guizhou Provincial Administration of Traditional Chinese Medicine, Grant No. QZYY-2024-016 and QZYY-2022-036; and the Talent research fund project of Anhui Agricultural University (No.rc392109). The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXL performed virulence assay, mouse survival assay, analysed the data and wrote the manuscript. KM performed KP clinical strain isolation, antimicrobials susceptibility tests and analysed the data. XL performed multilocus sequence typing and PCR. PC performed conjugation assay and revised the manuscript. LLL analyzed and interpreted clinical data. HYC was a major contributor in writing the manuscript. LMC designed the experiments and revised the manuscript. QYY conceived and designed the experiments, performed the study, analysed the data and revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSid Ahmed MA, Hamid JM, Hassan AMM, Abu Jarir S, Bashir Ibrahim E, Abdel Hadi H. Phenotypic and Genotypic Characterization of Pan-Drug-Resistant Klebsiella pneumoniae Isolated in Qatar. Antibiotics (Basel). 2024;13(3); doi: 10.3390/antibiotics13030275.\u003c/li\u003e\n\u003cli\u003eWang JL, Chen KY, Fang CT, Hsueh PR, Yang PC, Chang SC. Changing bacteriology of adult community-acquired lung abscess in Taiwan: Klebsiella pneumoniae versus anaerobes. Clin Infect Dis. 2005;40(7):915-22; doi: 10.1086/428574.\u003c/li\u003e\n\u003cli\u003ePaczosa MK, Mecsas J. 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Foodborne Pathog Dis. 2015;12(11):873-80; doi: 10.1089/fpd.2015.2025.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-microbiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mcro","sideBox":"Learn more about [BMC Microbiology](http://bmcmicrobiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/mcro","title":"BMC Microbiology","twitterHandle":"#bmcmicrobiology","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Klebsiella pneumoniae, susceptibility, clinical characteristics, virulence factors, resistance genes, transconjugants","lastPublishedDoi":"10.21203/rs.3.rs-5028260/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5028260/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eInfections caused by carbapenem-resistant hypervirulent \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e (CR-HVKP) pose a critical challenge in clinical management due to limited treatment options and high mortality. Elucidating their virulence determinants and resistance mechanisms is essential for optimizing antimicrobial strategies and improving patient outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe conducted a retrospective analysis of 102 carbapenem-resistant CRKP strains. Antimicrobial susceptibility testing was performed using the broth microdilution method, and resistance genotypes were characterized via PCR and Sanger sequencing. Virulence factors were identified through genomic sequencing and validated in a murine survival model (n=6 mice per strain). Conjugation assays were performed to assess the transferability of resistance and virulence genes, with recipient strain\u003cem\u003e E. coli\u003c/em\u003e J53, and transfer events were confirmed by PCR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e CRKP strains were predominantly derived from sputum-, urine- and blood-specimens. Patients with CRKP infections predominantly had pulmonary infections. CRKP exhibited high resistance to other β-lactam antibiotics, mainly due to the presence of \u003cem\u003ebla\u003c/em\u003e\u003csub\u003e\u003cem\u003eKPC-2\u003c/em\u003e\u003c/sub\u003e, high resistance to quinolones mediated by the carriage of \u003cem\u003eaac (6''-Ib-cr)\u003c/em\u003e, \u003cem\u003eQnrS \u003c/em\u003eand \u003cem\u003eQnrB\u003c/em\u003e, and high resistance to aminoglycosides mediated by the carriage of \u003cem\u003ermtB\u003c/em\u003e, \u003cem\u003eant(3'')-I\u003c/em\u003e and \u003cem\u003earmA\u003c/em\u003e. CR-HVKP is mainly composed of ST11. Aerobactin (\u003cem\u003eiucA, iutA\u003c/em\u003e), Ent siderophore (\u003cem\u003efepA, entB\u003c/em\u003e), Salmochelin (\u003cem\u003eiroN\u003c/em\u003e), Yersiniabactin (\u003cem\u003eybtS\u003c/em\u003e), Type 3 fimbriae (\u003cem\u003emrkD\u003c/em\u003e), Type I fimbriae (\u003cem\u003efimH\u003c/em\u003e), and Regulation (\u003csub\u003e\u003cem\u003ep\u003c/em\u003e\u003c/sub\u003e\u003cem\u003ermpA\u003c/em\u003e) were detected in the CR-HVKP isolates. The CR-HVKP strains had a median lethal dose (LD\u003csub\u003e50)\u003c/sub\u003e of 2 × 10\u003csup\u003e3\u003c/sup\u003e to 5 × 10\u003csup\u003e3\u003c/sup\u003e CFU in the mice, which was similar to that of the positive control NTUH-K2044. Conjugation assays revealed that the genes \u003cem\u003eiucA, iutA, iroN, \u003c/em\u003e\u003csub\u003e\u003cem\u003ep\u003c/em\u003e\u003c/sub\u003e\u003cem\u003ermpA\u003c/em\u003e, \u003cem\u003ebla\u003c/em\u003e\u003csub\u003e\u003cem\u003eKPC-2\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e, bla\u003c/em\u003e\u003csub\u003e\u003cem\u003eNDM-1\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e, bla\u003c/em\u003e\u003csub\u003e\u003cem\u003eVIM\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e, bla\u003c/em\u003e\u003csub\u003e\u003cem\u003eSHV-12\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e, bla\u003c/em\u003e\u003csub\u003e\u003cem\u003eTEM-1b\u003c/em\u003e\u003c/sub\u003e, \u003cem\u003eQnrA, QnrB, QnrS\u003c/em\u003e, and \u003cem\u003ermtB\u003c/em\u003e can be transferred to \u003cem\u003eE. coli\u003c/em\u003e J53. Compared with those of the recipient \u003cem\u003eE. coli\u003c/em\u003e J53, the MICs of meropenem, imipenem, levofloxacin and amikacin in the transconjugants increased by 4-128 times.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e These findings reveal that carbapenems in combination with aminoglycosides and quinolones may not be an effective option for the treatment of CRKP infections. Furthermore, the virulence and resistance genes may spread rapidly, which posing a public health risk and a significant threat to clinical care. Therefore, it is necessary to further strengthen hospital infection monitoring, prevention and control measures and to provide strict management and training on the rational use of antimicrobial agents in intensive care units.\u003c/p\u003e","manuscriptTitle":"Prevalence and molecular characterisation of multi-drug resistant ST11 hypervirulent Klebsiella pneumoniae in a teaching hospital","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-06 05:58:48","doi":"10.21203/rs.3.rs-5028260/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-08T09:45:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-08T09:33:26+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-08T03:53:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-04T16:01:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"91766229907948111429720117234886988695","date":"2025-04-28T14:31:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"23320570085667858651134146434856121175","date":"2025-04-25T15:03:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"131802901324228535385908833261295244487","date":"2025-04-24T06:50:53+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-24T05:55:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-24T05:14:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Microbiology","date":"2025-04-23T05:08:01+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-microbiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mcro","sideBox":"Learn more about [BMC Microbiology](http://bmcmicrobiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/mcro","title":"BMC Microbiology","twitterHandle":"#bmcmicrobiology","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bd8905ef-9bf0-4363-a522-35a97aa7807c","owner":[],"postedDate":"May 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-06-09T16:05:45+00:00","versionOfRecord":{"articleIdentity":"rs-5028260","link":"https://doi.org/10.1186/s12866-025-04052-x","journal":{"identity":"bmc-microbiology","isVorOnly":false,"title":"BMC Microbiology"},"publishedOn":"2025-06-06 15:57:17","publishedOnDateReadable":"June 6th, 2025"},"versionCreatedAt":"2025-05-06 05:58:48","video":"","vorDoi":"10.1186/s12866-025-04052-x","vorDoiUrl":"https://doi.org/10.1186/s12866-025-04052-x","workflowStages":[]},"version":"v1","identity":"rs-5028260","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5028260","identity":"rs-5028260","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}