Antibiotic resistance and occurrence of extended-spectrum beta-lactamases, AmpC and carbapenemases in Klebsiella pneumoniae from blood cultures in Southern Ghana

Antibiotic resistance and occurrence of extended-spectrum beta-lactamases, AmpC and carbapenemases in Klebsiella pneumoniae from blood cultures in Southern Ghana | 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 Antibiotic resistance and occurrence of extended-spectrum beta-lactamases, AmpC and carbapenemases in Klebsiella pneumoniae from blood cultures in Southern Ghana Francis K. M. Tetteh, William Boateng, Mary-Madgalene Osei, Fleischer C. N. Kotey, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9086605/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Antibiotic-resistant Klebsiella pneumoniae presents a significant global health threat, prompting urgent calls for new treatment options. This study determined antibiotic resistance profiles of K. pneumoniae isolates from blood cultures in Southern Ghana and characterized the β-lactamase enzymes mediating β-lactam resistance. Archived K. pneumoniae isolates stored at -80°C at the Department of Medical Microbiology, University of Ghana Medical School were retrieved and revived for the study. Isolate identities were confirmed using the BD Bruker MALDI-TOF. Antimicrobial susceptibility testing was performed using both the MicroScan AutoSCAN system and Kirby-Bauer disc diffusion method. Of the 109 non-duplicate archived isolates, 95 (87.2%) were confirmed as K. pneumoniae . All confirmed isolates exhibited resistance to at least one antibiotic class, with two isolates (2.1%) resistant to all tested antibiotics. High resistance rates were observed for trimethoprim-sulfamethoxazole (85.3%), gentamicin (83.2%), ceftriaxone (80.0%), cefotaxime (78.9%), and ceftazidime (77.9%). Resistance to ertapenem (18.9%), and meropenem (8.4%) was comparatively lower. β-Lactamase enzyme profiles revealed that 77.9% (n = 74/95) of screened isolates were extended-spectrum beta-lactamase (ESBL) producers, 51.6% (n = 47/91) were AmpC producers, 26.6% (n = 17/64) were carbapenemase-producers, and 12.5% (n = 6/48) exhibited resistance to colistin. Notably, 12.5% of isolates concurrently produced ESBL, AmpC, and carbapenemase enzymes and were resistant to colistin. The prevalence of ESBL-producing K. pneumoniae was higher among children under five years of age compared to adults over sixty, though the difference was not statistically significant ( p = 0.933). All ESBL-producing isolates were multidrug-resistant (MDR), and 76.2% (n = 21) of non-ESBL producers were also MDR. AmpC-producing isolates were significantly more prevalent among children under five than among those aged 5–19 and adults over sixty ( p = 0.023). The high prevalence of MDR K. pneumoniae strains producing ESBLs, AmpCs, carbapenemases, and exhibiting colistin resistance is alarming and significantly narrows treatment options for bloodstream infections. These findings highlight the urgent need for alternative therapeutic strategies and routine surveillance to guide effective clinical management and antimicrobial stewardship. Bacteriology Infectious Diseases Laboratory Diagnostics Klebsiella pneumoniae Extended-spectrum beta-lactamase AmpC Carbapenemase Colistin Figures Figure 1 Figure 2 Introduction Klebsiella pneumoniae is a Gram-negative, non-motile, encapsulated bacterium that has emerged as a medically significant multidrug-resistant (MDR) pathogen. It is implicated in both community- and hospital-acquired infections (CAIs and HAIs) 1 , 2 , 3 . The World Health Organization (WHO) has classified K. pneumoniae as a critical priority pathogen that warrants new antibiotics urgently 4 . Globally, it is the second most common cause of Gram-negative bacteremia 5 and the leading cause of neonatal sepsis in sub-Saharan Africa. 6 , 7 In 2019 alone, drug-resistant K. pneumoniae was associated with over 600,000 deaths in the region, 8 underscoring its major threat to public health in the context of rising antimicrobial resistance (AMR). AMR remains one of the most pressing threats to global public health. It leads to significant adverse outcomes, including prolonged hospital stays due to failed antimicrobial therapy, increased medical costs for patients and their families, overburdened healthcare systems, and elevated mortality rates. 4 , 9 , 10 In 2017, the WHO underscored the urgent need for low-and middle-income countries (LMICs) to strengthen their healthcare systems to combat AMR through the implementation of surveillance and antimicrobial stewardship programs. These programs aim to optimize antimicrobial use and prevent the further spread of resistant pathogens. 9 , 11 The clinical impact of K. pneumoniae is well documented, with increasing resistance observed against key antibiotics. Resistance to third-generation cephalosporins is commonly mediated by ESBLs and AmpC β-lactamases 12 . Resistance to last-resort antibiotics such as carbapenems is conferred by carbapenemase enzymes, 13 while resistance to colistin – a reserve antimicrobial is often linked to polymyxin E resistance. 14 In Enterobacteriaceae, antibiotic resistance mechanisms include drug target modification, efflux pumps, biofilm formation, enzymatic degradation (via ESBLs, AmpCs, and carbapenemases), global cell adaptation, and decreased membrane permeability due to porin loss 15 . These mechanisms collectively confer resistance to a broad spectrum of antibiotics, including cephalosporins, fluoroquinolones, and trimethoprim-sulfamethoxazole, 16 ultimately limiting treatment options by restricting, inactivating, or degrading antibiotics before they exert their effect. 14 , 15 , 16 While ESBLs and AmpCs can hydrolyze most penicillins and cephalosporins, they do not typically affect carbapenems 17 , 18 , 19 . However, rising global concern surrounds the increasing resistance to colistin in both human and veterinary settings, 20 including documented cases in Ghana. 21 , 22 Although MDR- K. pneumoniae has been reported worldwide, its prevalence in LMICs is particularly concerning. Clinical studies have reported ESBL-producing K. pneumoniae rates of 77.1% in Northeastern Thailand, 23 80% in Bangladesh, 24 and 84% in Côte d’Ivoire. 25 In Colombia, carbapenem resistant K. pneumoniae prevalence reached 91.5% in clinical isolates. 26 Across Africa, hospital-based studies have reported prevalence of carbapenemase-producing organisms ranging from 2.3% to 67.7% in North Africa, and 9% to 60% in sub-Saharan Africa. 2 Despite this, routine detection and characterization of resistance mechanisms are often lacking in diagnostic laboratories across LMICs, including Ghana – a situation that is common in many resource-constrained settings. 27 This gap in diagnostic capacity limits effective antimicrobial therapy and infection prevention efforts. To address these knowledge gaps, the present study evaluated the prevalence of ESBLs, AmpCs, carbapenemases, and colistin resistance; characterizes AMR patterns; and maps the distribution of these resistance traits among MDR- K. pneumoniae isolated from blood cultures in Ghana. The findings aim to inform empirical therapy and clinical decision-making through the rapid identification of resistance traits and their associated antibiotic resistance profiles, thereby enhancing patient care and treatment outcomes. Material and Methods Study design and isolate recovery Archived K. pneumoniae isolates preserved at -80°C in the Department of Medical Microbiology, University of Ghana Medical School, were retrieved and revived on July 4, 2023 for the study. The isolates had been collected between April and December 2021. A total of 109 freezer skimmed-milk tryptone glucose glycerol stock of the non-duplicate K. pneumoniae isolates were aseptically scraped using sterile pipette tips and inoculated into tryptic soy broth (TSB) (Oxoid, UK). After 24 ± 1 h incubation at 37°C, a loopful was plated onto nutrient agar (NA) (Oxoid, UK) and incubated at 37°C for 20 ± 1 h. Ninety-five (95) isolates were successfully revived and confirmed using the BD MALDI-TOF analyzer, Version 4.2.100 (BRUKER Daltonics, Germany). Patient demographics (age, sex), clinical diagnoses, and contributing health facilities from which the isolates emanated were extracted from the associated anonymized database. Antibiotic susceptibility testing and determination of resistance phenotypes Antibiotic susceptibility testing (AST) was conducted using the Kirby-Bauer disc diffusion method and the minimum inhibitory concentration (MIC) method on the MicroScan AutoSCAN-4 system (American MicroScan, USA) in accordance with the manufacturer’s instructions and interpreted using the clinical and laboratory standards institute (CLSI) M100 guidelines. 28 The AutoSCAN-4 was performed in the 96-well microplates as described previously. 29 Briefly, the isolates were inoculated into the microdilution panels containing preloaded antibiotics. The inoculated plates were then incubated for 20 ± 1 h at 37°C and scanned for absorbance representing growth. The AutoSCAN-4 performs automated AST in a 96-well microbroth dilution plate and is read by measuring the amount of light passing through the wells. 29 With the disc diffusion method, susceptibilities of isolates were examined against the following clinically relevant antibiotics: ampicillin (10 µg), ceftazidime (30 µg), cefotaxime (30 µg), ceftriaxone (30 µg), ciprofloxacin (5 µg), ertapenem (10 µg), meropenem (10 µg), tetracycline (30 µg), chloramphenicol (30 µg), gentamicin (10 µg), azithromycin (15 µg), and trimethoprim-sulfamethoxazole (1.25/23.75 µg) (Oxoid, UK). Reference strains Escherichia coli ATCC 25922 and K. pneumoniae NCTC 13438 were included as quality controls in each susceptibility assay and phenotypic test. The confirmed isolates were tested for the presence of resistance phenotypes, including ESBLs, AmpCs, and carbapenemases as well as resistance to colistin. The isolates were screened for presumptive presence of ESBLs using cefotaxime (30 µg), and ceftazidime (30 µg) antibiotic discs (MAST, UK). Isolates with zone inhibition diameters ≤ 27 mm for cefotaxime and ≤ 22 mm for ceftazidime were recorded as ESBL screened-positive. Confirmation for ESBL production was performed using the combined-discs method. Zones of inhibition were determined for each isolate to antibiotic disc containing 30 µg of cefotaxime, and 30 µg of ceftazidime either alone or in combination with 10 µg of clavulanic acid (MAST, UK). All zones of inhibition which differed by ≥ 5 mm between at least one of the standard antibiotic discs and its corresponding clavulanic combination disc were phenotypically confirmed as ESBL producers. The modified carbapenem inactivation method (mCIM), as described by Pierce et al . 30 , was used to detect carbapenemase production using meropenem (10 µg). Briefly, 1 µl of the K. pneumoniae isolate was mixed in a tube containing 2 ml of TSB using a sterile inoculation loop and vortexed for 10 to 15 s. Thereafter, a 10 µg meropenem disc was aseptically added into the bacterial suspension and incubated at 37°C for 4 h ± 15 m. Shortly before completing the 4-h carbapenem inactivation step, a suspension of the mCIM indicator organism ( E. coli ATCC 25922, a carbapenem-susceptible strain) adjusted to a 0.5 McFarland standard turbidity was prepared. The surface of a mueller hinton agar (MHA) plate was then inoculated following the standard disc diffusion susceptibility testing method. 28 The meropenem disc was then removed from the TSB bacterial suspension using a 10 µl inoculating loop, placed at the center of the inoculated MHA plate, and incubated aerobically at 37°C for 20 ± 1 h. The diameter of the zone of inhibition around each meropenem disc was measured and interpreted. A zone diameter of 6 to 10 mm was considered positive (carbapenemase production detected), a zone diameter of 11 to 19 mm was considered an indeterminate, and a zone diameter of ≥ 20 mm was considered as negative (no carbapenemase production detected) as previously reported. 31 , 32 Colistin resistance and AmpC were determined using the MicroScan AutoSCAN-4 system. Data analysis Data were entered into a Microsoft Excel® (2016) spreadsheet and exported into the IBM Statistical Products and Services Solutions (SPSS), Version 25 (IBM Corp., USA), for analysis. Descriptive statistics were computed, including means and standard deviation or medians and interquartile ranges for continuous variables, and frequencies and percentages for categorical variables. Differences in the prevalence of multidrug resistance by gender, age group, healthcare facility, region, and city were examined using Fisher’s exact test or the independent-samples t-test, as appropriate. Bar charts were generated using Microsoft Excel® (2016) to visualize antibiotic resistance profiles. Ninety-five percent confidence intervals (95% CIs) were calculated using the modified Wald method with the GraphPad QuickCalcs online calculator ( https://www.graphpad.com/quickcalcs/confinterval2/ ). A p-value < 0.05 was considered statistically significant. Results General characteristics of the study participants Of the 109 archived isolates, 95 (87.2%) were successfully revived and confirmed as K. pneumoniae. The mean age of the individuals from whom the isolates were recovered was 17.66 ± 24.68 years. Among patients with available sex data, 32 were male (mean age = 17.03 ± 24.57 years) and 31 were female (mean age = 17.84 ± 24.77 years). Data on sex and age were missing for 33.7% (32/95) and 27.4% (26/95) isolates, respectively. The majority of isolates were obtained from patients with a clinical diagnosis of sepsis (84.2%, 80/95), followed by bacteremia and chronic kidney disease (2.1%, 2/95 each). Eleven patients (11.6%) had other clinical conditions (Table 1 ). Table 1 Characteristics of study participants and phenotypic resistant traits among K. pneumoniae isolates from blood cultures Demographic Characteristics ESBL Producers (n = 74) AmpC Producers (n = 47) Carbapenemase Producers (n = 17) Colistin Resistant (n = 6) Category n = 95 (%) Frequency (%) 95% CI* p- Value Frequency (%) CI* (%) p -value Frequency (%) CI* (%) p- Value Frequency (%) CI* (%) p -value Sex Male 33.7 32.4 22.8–43.8 0.621 25.5 15.1–39.6 0.055 17.7 5.4–41.8 0.506 33.3 9.3–70.4 0.233 Female 32.6 35.1 25.2–46.5 27.7 16.8–41.9 29.4 13.0-53.4 50.0 18.8–81.2 Unknown 33.7 32.4 22.8–43.8 46.8 33.3–60.8 52.9 30.9–73.8 16.7 1.1–58.2 Age groups Under 5 years 40 40.5 30.1–51.9 0.933 25.5 15.1–39.6 0.023 17.6 5.4–41.8 0.210 33.3 9.3–70.4 0.272 5–19 years 8.4 9.5 4.4–18.5 8.5 2.8–20.5 17.6 5.4–41.8 33.3 9.3–70.4 20–59 years 13.7 13.5 7.3–23.3 17.0 8.6–30.4 5.9 0.0-28.9 16.7 1.1–58.2 60 + years 10.5 9.5 4.4–18.5 8.5 2.8–20.5 11.8 2.0-35.6 0.0 0.0-44.3 Unknown 27.4 27.0 18.2–38.2 40.4 27.6–54.7 47.1 26.2–69.0 Diagnosis Queried Sepsis 84.2 90.5 81.5–95.6 93.6 82.2–98.5 100.0 78.4–100.0 100.0 55.7–100.0 Bacteremia 2.1 2.7 0.2–9.9 0.879 4.3 0.4–15.0 0.822 0.0 0.0-21.6 0.715 0.0 0.0-44.3 0.715 Chronic kidney disorder 2.1 1.4 0.0–8.0 0.0 0.0–9.0 NT - NT - Others 11.6 5.4 1.7–13.5 2.1 0.0-12.1 0.0 0.0-21.6 0.0 0.0-44.3 Study site KATH 23.2 29.7 20.5–41.0 0.002 36.2 23.9–50.5 < 0.001 35.3 17.2–58.8 50 18.8–81.2 NA GARH 22.1 14.9 8.3–24.9 10.6 4.2–23.0 0.0 0.0-21.6 0.0 0.0-44.3 KBTH 17.9 16.2 9.4–26.4 25.5 15.1–39.6 35.3 17.2–58.8 0.0 0.0-44.3 ERH 12.6 10.8 5.3–20.2 17.0 8.6–30.4 23.5 9.1–47.8 50 18.8–81.2 37 MH 10.5 13.5 7.3–23.3 2.1 0.0-12.1 5.9 0.0-28.9 0.0 0.0-44.3 PMLCH 6.3 8.1 3.5–16.9 2.1 0.0-12.1 0.0 0.0-21.6 0.0 0.0-44.3 HTH 3.2 4.1 0.9–11.7 6.4 1.6–17.8 0.0 0.0-21.6 0.0 0.0-44.3 Private Lab 3.2 1.4 0.0–8.0 0.0 0.0–9.0 0.0 0.0-21.6 0.0 0.0-44.3 LEKMA Hospital 3.2 1.4 0.0–8.0 0.0 0.0–9.0 0.0 0.0-21.6 0.0 0.0-44.3 Regional Summary Greater Accra 61.1 55.4 44.1–66.2 0.021 40.4 27.6–54.7 0.001 41.2 21.6–64.1 0.0 0.0-44.3 0.010 Ashanti 23.2 29.7 20.5–41.0 36.2 23.9–50.5 35.3 17.2–58.8 50.0 18.8–81.2 Eastern 12.6 10.8 5.3–20.2 17.0 8.6–30.4 23.5 9.1–47.8 50.0 18.8–81.2 Volta 3.2 4.1 0.9–11.7 6.4 1.6–17.8 0.0 0.0-21.6 0.0 0.0-44.3 ESBL – Extended Spectrum Beta-Lactamase, KATH - Komfo Anokye Teaching Hospital, GARH - Greater Accra Regional Hospital, KBTH - Korle Bu Teaching Hospital, ERH - Eastern Regional Hospital, 37 MH − 37 Military Hospital, PMLCH - Princess Marie Louise Children’s Hospital, HTH – Ho Teaching Hospital, LEKMA - Ledzokuku-Krowor Municipal Assembly, n – Number, % - Percentage, NA – Not applicable, NT – Not tested, CI* - Confidence interval. Antibiotic susceptibility patterns of the isolates All isolates demonstrated resistance to at least one class of antibiotic, and two isolates (2.1%) were resistant to all antibiotics tested. Of the twelve antibiotics evaluated, nine exhibited resistance rates exceeding 50.0%, while resistance to chloramphenicol, ertapenem, and meropenem was 49.5%, 18.9%, and 8.4%, respectively. All isolates were resistant to ampicillin (100.0%). High resistance rates were also observed for trimethoprim-sulfamethoxazole (85.3%), gentamicin (83.2%), ceftriaxone (80.0%), cefotaxime (78.9%), and ceftazidime (77.9%) (Fig. 1 ). Multidrug resistance, defined as resistance to at least one agent in three or more antimicrobial classes, according to Magiorakos et al. , 33 was identified in 94.7% (90/95) of the isolates. Of the 95 isolates, 12.5% were concurrently ESBL-, AmpC-, and carbapenemase-producing, and were resistant to colistin. Overall, 77.9% (74/95) of isolates were ESBL-producing K. pneumoniae (77.9%). Although ESBL production appeared more frequent among isolates from children under five years of age (40.5%) compared with adults older than 60 years (9.5%), this difference was not statistically significant ( p = 0.933) (Table 1 ). The majority of ESBL-producing isolates originated from the Greater Accra Region (55.4%). At the facility level, ESBL producers were most prevalent at KBTH (16.2%), followed by GARH (14.9%), 37 MH (13.5%), PMLCH (8.1%), Private Lab (1.4%), and LEKMA Hospital (1.4%) (Table 1 ). ESBL-producing isolates demonstrated high resistance rates (often > 60%) to most antibiotics tested, including ampicillin, trimethoprim-sulfamethoxazole, ceftriaxone, gentamicin, cefotaxime, ceftazidime, tetracycline, azithromycin, ciprofloxacin, and chloramphenicol (Fig. 2 A). All ESBL-producing isolates (74/74; 100%) were MDR, compared with 76.2% (16/21) of non-ESBL-producing isolates. The majority of the isolates remained susceptible to meropenem and ertapenem. Detailed antimicrobial susceptibility and phenotypic test results are presented in supplementary table S1. Of the 91 isolates tested for AmpC production, 51.6% (47/91) were confirmed as AmpC-producers. Among these, 27.7% were recovered from females and 25.5% from males, while sex data were missing for 46.8% of isolates. The proportion of AmpC-producing K. pneumoniae was relatively higher among children under five years of age compared with individuals aged 5–19 years and adults older than 60 years (Table 1 ). Most AmpC-producing isolates originated from the Greater Accra Region (40.4%). At the facility level, AmpC-producers were most prevalent at KBTH (25.5%), followed by GARH (10.6%), PMLCH (2.1%), and 37 MH (2.1%). No AmpC-producing isolates were recorded from LEKMA Hospital or the Private Lab (Table 1 ). AmpC producing isolates demonstrated high resistance rates (> 60%) to most antibiotics tested, whereas non-AmpC producers exhibited moderate to high resistance across the antibiotics evaluated (Fig. 2 B). With the exception of one isolate, all AmpC producers (97.9%; 46/47) were MDR. Among non-AmpC producers, 90.9% (40/44) were MDR. Carbapenemase testing was performed on 64 isolates (due to resource constraints), of which 26.6% were confirmed as carbapenemase-producers. Among these, 29.4% were recovered from females and 17.6% from males, while sex data were missing for 52.9% of isolates. There was no statistically significant difference in carbapenemase-producing K. pneumoniae across the different age groups (Table 1 ). Most carbapenemase-producing isolates originated from the Greater Accra Region (41.2%). At the facility level, carbapenemase producers were most prevalent at KBTH (35.3%), followed by 37 MH (5.9%). However, none were recorded from GARH, PMLCH, Private Lab, and LEKMA (Table 1 ). Generally, carbapenemase producers demonstrated high resistance to the various antibiotics, while non-carbapenemase producers showed slightly high resistance to the antibiotics (Fig. 2 C). With the exception of one isolate, 94.1% (16/17) of carbapenemase producers were MDR. Similarly, 97.9% (46/47) of non-carbapenemase producers were MDR. Colistin susceptibility testing was performed on 48 isolates (due to resource constraints), of which 12.5% were confirmed as colistin-resistant. Among these, 50.0% were recovered from females, 33.3% from males, and sex data were missing for 16.7% of isolates. The proportion of colistin-resistant K. pneumoniae was similar among children under five and other age groups (5–19 years), with no statistically significant difference observed ( p = 0.272) (Table 1 ). No colistin-resistant isolates were identified from the Greater Accra Region. Colistin-resistant isolates exhibited very high resistance to most antibiotics tested, whereas colistin-susceptible isolates showed moderately high resistance across the same antibiotics. Although all colistin-resistant isolates (6/6; 100%) were MDR, they remained susceptible to meropenem and ertapenem (Fig. 2 D). Among colistin-susceptible isolates, 97.6% (40/41) were MDR. Discussion This study investigated the prevalence of antibiotic resistance and β-lactam-degrading enzymes specifically ESBLs, AmpCs, and carbapenemases among K. pneumoniae isolates recovered from blood cultures in Southern Ghana. A high prevalence of resistance was observed across nearly all antibiotics tested, except for meropenem and ertapenem, aligning with previous findings from Ghana, 34,35 and other regions. 36 , 37 Resistance to third-generation cephalosporins, including cefotaxime, ceftazidime, and ceftriaxone, is often linked to ESBL production. 38 Consequently, even if an isolate appears susceptible in vitro , treatment failure may occur if it harbors ESBL genes 38 . The high resistance rate to gentamicin, an aminoglycoside, observed in this study may be attributed to several mechanisms, including: (1) enzymatic inactivation by aminoglycoside-modifying enzymes such as acetyltransferases, nucleotidyltransferases, or phosphotransferases; (2) increased efflux; (3) reduced permeability; and (4) alterations in the 30S ribosomal subunit that prevent drug binding 39 . This is especially concerning given the widespread and often empiric use of aminoglycosides in Ghana, where they are among the most commonly prescribed antibiotics 40 , 41 , 42 . A six-year review at a Ghanaian secondary healthcare facility found gentamicin usage at a rate of 13.1 defined daily doses per 100 patients, with no significant reduction from 2016 to 2021 43 . The overuse and misuse of antibiotics particularly aminoglycosides, cephalosporins, and fluoroquinolones is a key driver of AMR and highlight the urgent need for stricter prescribing practices and improved surveillance. In contrast, meropenem and ertapenem retained relatively high effectiveness against MDR strains, consistent with reports from other settings. 44 , 45 Their limited use is likely attributable to their high cost, intravenous administration, and their designation as last-resort agents in national treatment guidelines. Although these carbapenems have been available in Ghana since 2002, their lower consumption compared with older antibiotics such as aminoglycosides, may have contributed to the preservation of their efficacy. Nevertheless, judicious use remains essential, and routine monitoring of carbapenem use should be emphasized as a key component of antimicrobial stewardship programs. The prevalence of ESBL production in this study (77.9%) was significantly higher than previous reports from China (12.1%) 46 , Italy (30%) 45 , and sub-Saharan Africa (45.5%) 47 . The elevated rate may reflect long-standing but under-recognized community circulation of ESBL-producing strains in Ghana, exacerbated by limited laboratory capacity and lack of awareness 19 . The prevalence reported here is comparable to studies in Egypt (76.2%) 48 , and Ghana (71.2%) 49 , (75.6%) 50 , though lower than figures from Bangladesh (80%) 24 , Belgium (89.3%) 51 , Egypt (80%) 52 , and Côte d’Ivoire 25 . Variations in ESBL prevalence likely stem from geographic, methodological, and temporal differences. ESBL prevalence was notably higher among children under five, though not statistically significant ( p = 0.933), likely due to increased empirical antibiotic use in this age group. MDR is strongly associated with ESBL production, and the high prevalence of MDR K. pneumoniae observed especially among ESBL producers is consistent with earlier findings from Ghana 53 , 54 , and other regions 55 , 56 . Resistance was particularly high for penicillins, trimethoprim-sulfonamide combinations, aminoglycosides, third-generation cephalosporins, tetracyclines, macrolides, and fluoroquinolones. This is alarming, as these antibiotics are frequently used empirically for syndromic treatment 57 . The increasing ineffectiveness of these drugs against MDR pathogens necessitates urgent, multifaceted public health interventions, including enhanced diagnostics, refined treatment protocols, and robust infection control measures. AmpC production was detected in 51.6% of isolates significantly higher than previous reports from Saudi Arabia (5.5%) 58 , Libya (6.7%) 59 , and Ghana (19.4%) 49 , (17%) 60 , but comparable to a study from Iran (52.9%) 61 . AmpC prevalence remains underdefined in sub-Saharan Africa due to the absence of rapid, validated detection methods 58 . Consequently, its burden may be underestimated, underscoring the need to develop and implement standardized detection protocols 62 . Carbapenemase production was detected in 26.6% of isolates – significantly higher than previously reported rates in Ghana: 5.6% by Dwomoh et al. 53 , 2.9% by Codjoe et al. 63 , and 7.2% by Hackman et al. 64 . The present study’s focus on K. pneumoniae from blood cultures in secondary and tertiary hospitals in Southern Ghana may account for this higher prevalence. The findings align with a recent Ghanaian study reporting 26.4% prevalence 49 , and with similar findings from Uganda 65 , though still lower than those from Egypt (54.1%) 66 . Elsewhere, reported carbapenemase rates vary 4.9% in Argentina 67 , 5.74% in Malaysia 68 , and 9.1% in Nepal 69 , but collectively point to a global rise in carbapenem resistance, requiring urgent, coordinated responses. Colistin resistance was identified in 12.5% of isolates comparable to rates from Kuwait (12.0%) 37 , and Spain (13.1) 55 , but lower than those reported in India (33.3%) 14 , Italy (43%) 56 , and Ghana (57%) 22 . These variations may reflect differences in antibiotic use practices, population demographics, resistance trends, and detection methods. The absence of standardized, rapid colistin resistance testing and lack of consistent antimicrobial use guidelines compounded by limited public awareness remains a challenge, especially given colistin’s role as a last-resort antibiotic for MDR Gram-negative infections. Many healthcare facilities in resource-limited settings lack the diagnostic capacity to detect colistin resistance 27 , leading to its underreporting. Although the prevalence found here is relatively low, regular nationwide surveillance is essential. This study has certain limitations. Archived isolates were used, limiting access to detailed clinical data such as underlying conditions or comorbidities. Nonetheless, inclusion of isolates from both secondary and tertiary care facilities across Southern Ghana enhances the study’s representativeness and generalizability. Conclusion This study reveals a high prevalence of ESBL, AmpC, carbapenemase production, and colistin resistance among K. pneumoniae isolates from blood cultures in Southern Ghana. Notably, a subset of isolates harbored all three β-lactamase enzymes and were concurrently resistant to colistin, presenting a significant therapeutic challenge. Routine detection and characterization of resistance mechanisms, coupled with robust laboratory surveillance, are urgently needed to guide effective clinical management and containment strategies. The responsible use of last-resort antibiotics such as meropenem and ertapenem must be prioritized, while the overuse of third-generation cephalosporins, aminoglycosides, and fluoroquinolones should be strictly regulated. The widespread presence of MDR K. pneumoniae in both ESBL-producing and non-ESBL-producing isolates, as well as AmpC-producing and non-AmpC-producing isolates, and carbapenemase-producing and non-carbapenemase-producing isolates underscores the urgent need to enhance infection-prevention and control measures. Strengthening antimicrobial stewardship programs within both healthcare facilities and communities is essential to curb the spread of resistance and preserve the efficacy of available antibiotics. Declarations Acknowledgements The authors are highly grateful to all staff of the Microbiology Departments in all nine sentinel sites, all staff of the Department of Medical Microbiology, College of Health Sciences, Korle-Bu, especially Joseph Anamsi, Grace Semevor, Rita Serwaa Addo, Ursela Serwaa Sarfo, and Isaura Namen-Arikum Yelkebono for their enormous technical support during the study. Author contributions Conceptualization: FKMT, WB, KOD, and ES-D. Methodology: FKMT, MMO, FCNK, BD, and KOD. Validation: FKMT, MMO, FCNK, BD, KOD, and ES-D. Formal analysis: FKMT, WB, BD, and KOD. Investigation: FKMT. Data curation: FKMT, WB, MMO, FCNK, and BD. Writing - original draft preparation: FKMT. Writing - review and editing: FKMT, WB, KOD, and ES-D. Visualization: FKMT, WB, MMO, FCNK, BD, KOD, and ES-D. Supervision: KOD, and ES-D. Resources: FKMT, MMO, FCNK, and ES-D. Project administration: FKMT, MMO, FCNK, and ES-D. All authors reviewed final draft of the manuscript and approved for submission. Declaration of competing interests The authors declare no competing interests. Data availability All data generated or analyzed during the study are included in this article. Further inquiries can be directed to the corresponding authors. Ethical approval The Ethical and Protocol Review Committee (EPRC) of the College of Health Sciences, University of Ghana, approved the research study (protocol identification number: CHS-Et/M.2-P4.6/2021-2022). Approval was also obtained from the respective study sites. Informed consent was waived by the ethics committee because there was no contact with patients. Archived bacterial isolates were retrieved and used. The isolates had been de-identified prior to retrieval. All methods were performed in accordance with the relevant standard guidelines and regulations. Funding FKMT was supported with a Doctoral Fellowship Award “ST/PhD/004/2022” from the West Africa Genomic Medicine Centre (WAGMC), University of Ghana. The views expressed in this publication are those of the authors and not necessarily those of the University of Ghana or the WAGMC. References Olalekan A et al (2020) High proportion of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae among extended-spectrum β-lactamase-producers in Nigerian hospitals. J Global Antimicrob Resist 21:8–12 Manenzhe RI, Zar HJ, Nicol MP, Kaba M (2015) The spread of carbapenemase-producing bacteria in Africa: a systematic review. 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Infect Drug Resist 18:4993–5005 Toy T et al (2019) Multicountry Distribution and Characterization of Extended-spectrum β-Lactamase–associated Gram-negative Bacteria From Bloodstream Infections in Sub-Saharan Africa. Clin Infect Dis 69:S449–S458 El-Kholy A et al (2012) Device-associated nosocomial infection rates in intensive care units at Cairo University hospitals: first step toward initiating surveillance programs in a resource-limited country. Am J Infect Control 40:e216–220 Quansah E et al (2019) Geographical Distribution of β-Lactam Resistance among Klebsiella spp. from Selected Health Facilities in Ghana. Trop Med Infect Disease 4:117 Labi A-K et al (2020) High Carriage Rates of Multidrug-Resistant Gram-Negative Bacteria in Neonatal Intensive Care Units From Ghana. 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Rev Esp Quimioter 14:358–363 Monaco M et al (2014) Colistin resistance superimposed to endemic carbapenem-resistant Klebsiella pneumoniae: a rapidly evolving problem in Italy, November 2013 to April 2014. Eurosurveillance 19:20939 Ntirenganya C, Manzi O, Muvunyi CM, Ogbuagu O (2015) High Prevalence of Antimicrobial Resistance Among Common Bacterial Isolates in a Tertiary Healthcare Facility in Rwanda. Am J Trop Med Hyg 92:865–870 Abdalhamid B, Albunayan S, Shaikh A, Elhadi N, Aljindan R (2017) Prevalence study of plasmid-mediated AmpC β-lactamases in Enterobacteriaceae lacking inducible ampC from Saudi hospitals. J Med Microbiol 66:1286–1290 Ahmed SF, Ali MMM, Mohamed ZK, Moussa TA, Klena JD (2014) Fecal carriage of extended-spectrum β-lactamases and AmpC-producing Escherichia coli in a Libyan community. Ann Clin Microbiol Antimicrob 13:22 Owusu FA et al (2023) Occurrence of Carbapenemases, Extended-Spectrum Beta-Lactamases and AmpCs among Beta-Lactamase-Producing Gram-Negative Bacteria from Clinical Sources in Accra, Ghana. Antibiotics 12, 1016 Ghanavati R et al (2017) First report of coexistence of AmpC beta-lactamase genes in Klebsiella pneumoniae strains isolated from burn patients. Acta Microbiol Immunol Hung 64:455–462 Rodríguez-Guerrero E, Callejas-Rodelas JC, Navarro-Marí JM, Gutiérrez-Fernández J (2022) Systematic Review of Plasmid AmpC Type Resistances in Escherichia coli and Klebsiella pneumoniae and Preliminary Proposal of a Simplified Screening Method for ampC. Microorganisms 10:611 Codjoe FS, Donkor ES, Smith TJ, Miller K (2019) Phenotypic and Genotypic Characterization of Carbapenem-Resistant Gram-Negative Bacilli Pathogens from Hospitals in Ghana. Microb Drug Resist 25:1449–1457 Hackman HK, Arhin RE, Gordon A, Mensah S (2017) N. B. Emergence of Carbapenem-resistant Enterobacteriaceae among Extended-spectrum Beta-lactamase Producers in Accra, Ghana. J Nat Sci Res 7 Okoche D, Asiimwe BB, Katabazi FA, Kato L, Najjuka CF (2015) Prevalence and Characterization of Carbapenem-Resistant Enterobacteriaceae Isolated from Mulago National Referral Hospital, Uganda. PLoS ONE 10:e0135745 Kotb S et al (2020) Epidemiology of Carbapenem-resistant Enterobacteriaceae in Egyptian intensive care units using National Healthcare–associated Infections Surveillance Data, 2011–2017. Antimicrob Resist Infect Control 9:2 Villar HE, Baserni MN, Jugo MB (2013) Faecal carriage of ESBL-producing Enterobacteriaceae and carbapenem-resistant Gram-negative bacilli in community settings. J Infect Developing Ctries 7:630–634 Zaidah AR, Mohammad NI, Suraiya S, Harun A (2017) High burden of Carbapenem-resistant Enterobacteriaceae (CRE) fecal carriage at a teaching hospital: cost-effectiveness of screening in low-resource setting. Antimicrob Resist Infect Control 6:42 Gurung S et al (2020) Detection of OXA-48 Gene in Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae from Urine Samples. Infect Drug Resist 13:2311–2321 Additional Declarations The authors declare no competing interests. Supplementary Files SupplementaryTableS1.docx Table S1: List of K. pneumoniae from blood cultures with their antimicrobial susceptibility and phenotypic test results. Cite Share Download PDF Status: Posted Version 1 posted 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-9086605","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":604010456,"identity":"8b035dd4-2807-4480-9a1c-53b2844afabe","order_by":0,"name":"Francis K. M. 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Each bar presents an antibiotic that denotes the percentage resistance.\u003c/p\u003e","description":"","filename":"Slide1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9086605/v1/fa13b9373dea931214414985.jpg"},{"id":104491873,"identity":"8f6251e2-47bd-42fb-b867-13d5f5fc466e","added_by":"auto","created_at":"2026-03-12 11:53:04","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":136320,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAntibiogram of \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eK. pneumoniae\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e phenotypes from blood cultures in Southern Ghana between April and December 2021. (A) \u003c/strong\u003eAntibiogram of ESBL (n=95), \u003cstrong\u003e(B)\u003c/strong\u003e AmpC (n=91), \u003cstrong\u003e(C)\u003c/strong\u003ecarbapenemase (n=64), and \u003cstrong\u003e(D)\u003c/strong\u003ecolistin (n=48).\u003cstrong\u003e \u003c/strong\u003eAntibiotics: ampicillin (10 µg), ceftazidime (30 µg), cefotaxime (30 µg), ceftriaxone (30 µg), ciprofloxacin (5 µg), ertapenem (10 µg), meropenem (10 µg), tetracycline (30 µg), chloramphenicol (30 µg), gentamicin (10 µg), azithromycin (15 µg), and trimethoprim-sulfamethoxazole (1.25/23.75 µg).\u003cstrong\u003e *\u003c/strong\u003eSignificant difference between ESBL-producers and non-ESBL-producers.\u003c/p\u003e","description":"","filename":"Slide2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9086605/v1/b5328dce5643b428e624ddf7.jpg"},{"id":104780675,"identity":"0e0e12cb-78a9-44ba-998e-339bbcb7b1d4","added_by":"auto","created_at":"2026-03-17 07:53:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1385907,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9086605/v1/60cd4dd9-9252-481c-92bf-47fde9b62c87.pdf"},{"id":104491871,"identity":"ca219689-640c-4033-b8c6-4b5f8dad9264","added_by":"auto","created_at":"2026-03-12 11:53:04","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":61943,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTable S1: List of \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eK. pneumoniae\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e from blood cultures with their antimicrobial susceptibility and phenotypic test results.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"SupplementaryTableS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-9086605/v1/b6334720ffebaf74882aadea.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eAntibiotic resistance and occurrence of extended-spectrum beta-lactamases, AmpC and carbapenemases in \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eKlebsiella\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003epneumoniae\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e from blood cultures in Southern Ghana\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003e \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e is a Gram-negative, non-motile, encapsulated bacterium that has emerged as a medically significant multidrug-resistant (MDR) pathogen. It is implicated in both community- and hospital-acquired infections (CAIs and HAIs)\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. The World Health Organization (WHO) has classified \u003cem\u003eK. pneumoniae\u003c/em\u003e as a critical priority pathogen that warrants new antibiotics urgently\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Globally, it is the second most common cause of Gram-negative bacteremia\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e and the leading cause of neonatal sepsis in sub-Saharan Africa.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e In 2019 alone, drug-resistant \u003cem\u003eK. pneumoniae\u003c/em\u003e was associated with over 600,000 deaths in the region,\u003csup\u003e8\u003c/sup\u003e underscoring its major threat to public health in the context of rising antimicrobial resistance (AMR).\u003c/p\u003e \u003cp\u003eAMR remains one of the most pressing threats to global public health. It leads to significant adverse outcomes, including prolonged hospital stays due to failed antimicrobial therapy, increased medical costs for patients and their families, overburdened healthcare systems, and elevated mortality rates.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e In 2017, the WHO underscored the urgent need for low-and middle-income countries (LMICs) to strengthen their healthcare systems to combat AMR through the implementation of surveillance and antimicrobial stewardship programs. These programs aim to optimize antimicrobial use and prevent the further spread of resistant pathogens.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe clinical impact of \u003cem\u003eK. pneumoniae\u003c/em\u003e is well documented, with increasing resistance observed against key antibiotics. Resistance to third-generation cephalosporins is commonly mediated by ESBLs and AmpC β-lactamases\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Resistance to last-resort antibiotics such as carbapenems is conferred by carbapenemase enzymes,\u003csup\u003e13\u003c/sup\u003e while resistance to colistin \u0026ndash; a reserve antimicrobial is often linked to polymyxin E resistance.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e In Enterobacteriaceae, antibiotic resistance mechanisms include drug target modification, efflux pumps, biofilm formation, enzymatic degradation (via ESBLs, AmpCs, and carbapenemases), global cell adaptation, and decreased membrane permeability due to porin loss\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. These mechanisms collectively confer resistance to a broad spectrum of antibiotics, including cephalosporins, fluoroquinolones, and trimethoprim-sulfamethoxazole,\u003csup\u003e16\u003c/sup\u003e ultimately limiting treatment options by restricting, inactivating, or degrading antibiotics before they exert their effect.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e While ESBLs and AmpCs can hydrolyze most penicillins and cephalosporins, they do not typically affect carbapenems\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. However, rising global concern surrounds the increasing resistance to colistin in both human and veterinary settings,\u003csup\u003e20\u003c/sup\u003e including documented cases in Ghana.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Although MDR-\u003cem\u003eK. pneumoniae\u003c/em\u003e has been reported worldwide, its prevalence in LMICs is particularly concerning.\u003c/p\u003e \u003cp\u003eClinical studies have reported ESBL-producing \u003cem\u003eK. pneumoniae\u003c/em\u003e rates of 77.1% in Northeastern Thailand,\u003csup\u003e23\u003c/sup\u003e 80% in Bangladesh,\u003csup\u003e24\u003c/sup\u003e and 84% in C\u0026ocirc;te d\u0026rsquo;Ivoire.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e In Colombia, carbapenem resistant \u003cem\u003eK. pneumoniae\u003c/em\u003e prevalence reached 91.5% in clinical isolates.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e Across Africa, hospital-based studies have reported prevalence of carbapenemase-producing organisms ranging from 2.3% to 67.7% in North Africa, and 9% to 60% in sub-Saharan Africa.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Despite this, routine detection and characterization of resistance mechanisms are often lacking in diagnostic laboratories across LMICs, including Ghana \u0026ndash; a situation that is common in many resource-constrained settings.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e This gap in diagnostic capacity limits effective antimicrobial therapy and infection prevention efforts. To address these knowledge gaps, the present study evaluated the prevalence of ESBLs, AmpCs, carbapenemases, and colistin resistance; characterizes AMR patterns; and maps the distribution of these resistance traits among MDR-\u003cem\u003eK. pneumoniae\u003c/em\u003e isolated from blood cultures in Ghana. The findings aim to inform empirical therapy and clinical decision-making through the rapid identification of resistance traits and their associated antibiotic resistance profiles, thereby enhancing patient care and treatment outcomes.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and isolate recovery\u003c/h2\u003e \u003cp\u003eArchived \u003cem\u003eK. pneumoniae\u003c/em\u003e isolates preserved at -80\u0026deg;C in the Department of Medical Microbiology, University of Ghana Medical School, were retrieved and revived on July 4, 2023 for the study. The isolates had been collected between April and December 2021. A total of 109 freezer skimmed-milk tryptone glucose glycerol stock of the non-duplicate \u003cem\u003eK. pneumoniae\u003c/em\u003e isolates were aseptically scraped using sterile pipette tips and inoculated into tryptic soy broth (TSB) (Oxoid, UK). After 24\u0026thinsp;\u0026plusmn;\u0026thinsp;1 h incubation at 37\u0026deg;C, a loopful was plated onto nutrient agar (NA) (Oxoid, UK) and incubated at 37\u0026deg;C for 20\u0026thinsp;\u0026plusmn;\u0026thinsp;1 h. Ninety-five (95) isolates were successfully revived and confirmed using the BD MALDI-TOF analyzer, Version 4.2.100 (BRUKER Daltonics, Germany). Patient demographics (age, sex), clinical diagnoses, and contributing health facilities from which the isolates emanated were extracted from the associated anonymized database.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAntibiotic susceptibility testing and determination of resistance phenotypes\u003c/h3\u003e\n\u003cp\u003eAntibiotic susceptibility testing (AST) was conducted using the Kirby-Bauer disc diffusion method and the minimum inhibitory concentration (MIC) method on the MicroScan AutoSCAN-4 system (American MicroScan, USA) in accordance with the manufacturer\u0026rsquo;s instructions and interpreted using the clinical and laboratory standards institute (CLSI) M100 guidelines.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e The AutoSCAN-4 was performed in the 96-well microplates as described previously.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e Briefly, the isolates were inoculated into the microdilution panels containing preloaded antibiotics. The inoculated plates were then incubated for 20\u0026thinsp;\u0026plusmn;\u0026thinsp;1 h at 37\u0026deg;C and scanned for absorbance representing growth. The AutoSCAN-4 performs automated AST in a 96-well microbroth dilution plate and is read by measuring the amount of light passing through the wells.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e With the disc diffusion method, susceptibilities of isolates were examined against the following clinically relevant antibiotics: ampicillin (10 \u0026micro;g), ceftazidime (30 \u0026micro;g), cefotaxime (30 \u0026micro;g), ceftriaxone (30 \u0026micro;g), ciprofloxacin (5 \u0026micro;g), ertapenem (10 \u0026micro;g), meropenem (10 \u0026micro;g), tetracycline (30 \u0026micro;g), chloramphenicol (30 \u0026micro;g), gentamicin (10 \u0026micro;g), azithromycin (15 \u0026micro;g), and trimethoprim-sulfamethoxazole (1.25/23.75 \u0026micro;g) (Oxoid, UK). Reference strains \u003cem\u003eEscherichia coli\u003c/em\u003e ATCC 25922 and \u003cem\u003eK. pneumoniae\u003c/em\u003e NCTC 13438 were included as quality controls in each susceptibility assay and phenotypic test.\u003c/p\u003e \u003cp\u003eThe confirmed isolates were tested for the presence of resistance phenotypes, including ESBLs, AmpCs, and carbapenemases as well as resistance to colistin. The isolates were screened for presumptive presence of ESBLs using cefotaxime (30 \u0026micro;g), and ceftazidime (30 \u0026micro;g) antibiotic discs (MAST, UK). Isolates with zone inhibition diameters\u0026thinsp;\u0026le;\u0026thinsp;27 mm for cefotaxime and \u0026le;\u0026thinsp;22 mm for ceftazidime were recorded as ESBL screened-positive. Confirmation for ESBL production was performed using the combined-discs method. Zones of inhibition were determined for each isolate to antibiotic disc containing 30 \u0026micro;g of cefotaxime, and 30 \u0026micro;g of ceftazidime either alone or in combination with 10 \u0026micro;g of clavulanic acid (MAST, UK). All zones of inhibition which differed by \u0026ge;\u0026thinsp;5 mm between at least one of the standard antibiotic discs and its corresponding clavulanic combination disc were phenotypically confirmed as ESBL producers.\u003c/p\u003e \u003cp\u003eThe modified carbapenem inactivation method (mCIM), as described by Pierce \u003cem\u003eet al\u003c/em\u003e.\u003csup\u003e30\u003c/sup\u003e, was used to detect carbapenemase production using meropenem (10 \u0026micro;g). Briefly, 1 \u0026micro;l of the \u003cem\u003eK. pneumoniae\u003c/em\u003e isolate was mixed in a tube containing 2 ml of TSB using a sterile inoculation loop and vortexed for 10 to 15 s. Thereafter, a 10 \u0026micro;g meropenem disc was aseptically added into the bacterial suspension and incubated at 37\u0026deg;C for 4 h\u0026thinsp;\u0026plusmn;\u0026thinsp;15 m. Shortly before completing the 4-h carbapenem inactivation step, a suspension of the mCIM indicator organism (\u003cem\u003eE. coli\u003c/em\u003e ATCC 25922, a carbapenem-susceptible strain) adjusted to a 0.5 McFarland standard turbidity was prepared. The surface of a mueller hinton agar (MHA) plate was then inoculated following the standard disc diffusion susceptibility testing method.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e The meropenem disc was then removed from the TSB bacterial suspension using a 10 \u0026micro;l inoculating loop, placed at the center of the inoculated MHA plate, and incubated aerobically at 37\u0026deg;C for 20\u0026thinsp;\u0026plusmn;\u0026thinsp;1 h. The diameter of the zone of inhibition around each meropenem disc was measured and interpreted. A zone diameter of 6 to 10 mm was considered positive (carbapenemase production detected), a zone diameter of 11 to 19 mm was considered an indeterminate, and a zone diameter of \u0026ge;\u0026thinsp;20 mm was considered as negative (no carbapenemase production detected) as previously reported.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e Colistin resistance and AmpC were determined using the MicroScan AutoSCAN-4 system.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003eData were entered into a Microsoft Excel\u0026reg; (2016) spreadsheet and exported into the IBM Statistical Products and Services Solutions (SPSS), Version 25 (IBM Corp., USA), for analysis. Descriptive statistics were computed, including means and standard deviation or medians and interquartile ranges for continuous variables, and frequencies and percentages for categorical variables. Differences in the prevalence of multidrug resistance by gender, age group, healthcare facility, region, and city were examined using Fisher\u0026rsquo;s exact test or the independent-samples t-test, as appropriate. Bar charts were generated using Microsoft Excel\u0026reg; (2016) to visualize antibiotic resistance profiles. Ninety-five percent confidence intervals (95% CIs) were calculated using the modified Wald method with the GraphPad QuickCalcs online calculator (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.graphpad.com/quickcalcs/confinterval2/\u003c/span\u003e\u003cspan address=\"https://www.graphpad.com/quickcalcs/confinterval2/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). A \u003cem\u003ep-value\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eGeneral characteristics of the study participants\u003c/h2\u003e \u003cp\u003eOf the 109 archived isolates, 95 (87.2%) were successfully revived and confirmed as \u003cem\u003eK. pneumoniae.\u003c/em\u003e The mean age of the individuals from whom the isolates were recovered was 17.66\u0026thinsp;\u0026plusmn;\u0026thinsp;24.68 years. Among patients with available sex data, 32 were male (mean age\u0026thinsp;=\u0026thinsp;17.03\u0026thinsp;\u0026plusmn;\u0026thinsp;24.57 years) and 31 were female (mean age\u0026thinsp;=\u0026thinsp;17.84\u0026thinsp;\u0026plusmn;\u0026thinsp;24.77 years). Data on sex and age were missing for 33.7% (32/95) and 27.4% (26/95) isolates, respectively. The majority of isolates were obtained from patients with a clinical diagnosis of sepsis (84.2%, 80/95), followed by bacteremia and chronic kidney disease (2.1%, 2/95 each). Eleven patients (11.6%) had other clinical conditions (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of study participants and phenotypic resistant traits among \u003cem\u003eK. pneumoniae\u003c/em\u003e isolates from blood cultures\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"14\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDemographic Characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eESBL Producers (n\u0026thinsp;=\u0026thinsp;74)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eAmpC Producers (n\u0026thinsp;=\u0026thinsp;47)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c11\" namest=\"c9\"\u003e \u003cp\u003eCarbapenemase Producers (n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003eColistin Resistant (n\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;95 (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequency (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95% CI*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep-\u003c/em\u003eValue\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFrequency (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCI* (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eFrequency (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCI* (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cem\u003ep-\u003c/em\u003eValue\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eFrequency (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCI* (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22.8\u0026ndash;43.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.621\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e25.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e15.1\u0026ndash;39.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.055\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e17.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5.4\u0026ndash;41.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.506\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e33.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e9.3\u0026ndash;70.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.233\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25.2\u0026ndash;46.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e27.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e16.8\u0026ndash;41.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e29.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e13.0-53.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e50.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e18.8\u0026ndash;81.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22.8\u0026ndash;43.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e46.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e33.3\u0026ndash;60.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e52.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e30.9\u0026ndash;73.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e16.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1.1\u0026ndash;58.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge groups\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnder 5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30.1\u0026ndash;51.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.933\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e25.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e15.1\u0026ndash;39.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u003cb\u003e0.023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e17.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5.4\u0026ndash;41.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.210\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e33.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e9.3\u0026ndash;70.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.272\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u0026ndash;19 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.4\u0026ndash;18.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.8\u0026ndash;20.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e17.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5.4\u0026ndash;41.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e33.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e9.3\u0026ndash;70.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u0026ndash;59 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.3\u0026ndash;23.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e17.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e8.6\u0026ndash;30.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.0-28.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e16.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e1.1\u0026ndash;58.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e60\u0026thinsp;+\u0026thinsp;years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.4\u0026ndash;18.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.8\u0026ndash;20.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e11.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2.0-35.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.0-44.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18.2\u0026ndash;38.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e40.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e27.6\u0026ndash;54.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e47.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e26.2\u0026ndash;69.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiagnosis Queried\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSepsis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e90.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e81.5\u0026ndash;95.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e93.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e82.2\u0026ndash;98.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e78.4\u0026ndash;100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e55.7\u0026ndash;100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBacteremia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2\u0026ndash;9.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.879\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.4\u0026ndash;15.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.822\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.0-21.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0.715\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.0-44.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e0.715\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic kidney disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0\u0026ndash;8.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.0\u0026ndash;9.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.7\u0026ndash;13.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.0-12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.0-21.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.0-44.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStudy site\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKATH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20.5\u0026ndash;41.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"8\" rowspan=\"9\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e36.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e23.9\u0026ndash;50.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e35.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e17.2\u0026ndash;58.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\" morerows=\"4\" rowspan=\"5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e18.8\u0026ndash;81.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGARH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8.3\u0026ndash;24.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e10.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.2\u0026ndash;23.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.0-21.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.0-44.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKBTH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9.4\u0026ndash;26.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e25.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e15.1\u0026ndash;39.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e35.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e17.2\u0026ndash;58.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.0-44.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eERH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.3\u0026ndash;20.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e17.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e8.6\u0026ndash;30.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e23.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e9.1\u0026ndash;47.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e18.8\u0026ndash;81.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e37 MH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.3\u0026ndash;23.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.0-12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.0-28.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.0-44.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePMLCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.5\u0026ndash;16.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.0-12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"3\" rowspan=\"4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.0-21.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\" morerows=\"3\" rowspan=\"4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.0-44.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"3\" rowspan=\"4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHTH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9\u0026ndash;11.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.6\u0026ndash;17.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.0-21.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.0-44.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrivate Lab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0\u0026ndash;8.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.0\u0026ndash;9.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.0-21.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.0-44.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLEKMA Hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.0\u0026ndash;8.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.0\u0026ndash;9.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.0-21.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.0-44.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRegional Summary\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGreater Accra\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e55.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e44.1\u0026ndash;66.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003e0.021\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e40.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e27.6\u0026ndash;54.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e41.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e21.6\u0026ndash;64.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.0-44.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0.010\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAshanti\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20.5\u0026ndash;41.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e36.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e23.9\u0026ndash;50.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e35.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e17.2\u0026ndash;58.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e50.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e18.8\u0026ndash;81.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEastern\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.3\u0026ndash;20.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e17.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e8.6\u0026ndash;30.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e23.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e9.1\u0026ndash;47.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e50.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e18.8\u0026ndash;81.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.9\u0026ndash;11.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.6\u0026ndash;17.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.0-21.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003e0.0-44.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eESBL \u0026ndash; Extended Spectrum Beta-Lactamase, KATH - Komfo Anokye Teaching Hospital, GARH - Greater Accra Regional Hospital, KBTH - Korle Bu Teaching Hospital, ERH - Eastern Regional Hospital, 37 MH\u0026thinsp;\u0026minus;\u0026thinsp;37 Military Hospital, PMLCH - Princess Marie Louise Children\u0026rsquo;s Hospital, HTH \u0026ndash; Ho Teaching Hospital, LEKMA - Ledzokuku-Krowor Municipal Assembly, n \u0026ndash; Number, % - Percentage, NA \u0026ndash; Not applicable, NT \u0026ndash; Not tested, CI* - Confidence interval.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eAntibiotic susceptibility patterns of the isolates\u003c/h2\u003e \u003cp\u003eAll isolates demonstrated resistance to at least one class of antibiotic, and two isolates (2.1%) were resistant to all antibiotics tested. Of the twelve antibiotics evaluated, nine exhibited resistance rates exceeding 50.0%, while resistance to chloramphenicol, ertapenem, and meropenem was 49.5%, 18.9%, and 8.4%, respectively. All isolates were resistant to ampicillin (100.0%). High resistance rates were also observed for trimethoprim-sulfamethoxazole (85.3%), gentamicin (83.2%), ceftriaxone (80.0%), cefotaxime (78.9%), and ceftazidime (77.9%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Multidrug resistance, defined as resistance to at least one agent in three or more antimicrobial classes, according to Magiorakos \u003cem\u003eet al.\u003c/em\u003e,\u003csup\u003e33\u003c/sup\u003e was identified in 94.7% (90/95) of the isolates.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOf the 95 isolates, 12.5% were concurrently ESBL-, AmpC-, and carbapenemase-producing, and were resistant to colistin. Overall, 77.9% (74/95) of isolates were ESBL-producing \u003cem\u003eK. pneumoniae\u003c/em\u003e (77.9%). Although ESBL production appeared more frequent among isolates from children under five years of age (40.5%) compared with adults older than 60 years (9.5%), this difference was not statistically significant (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.933) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The majority of ESBL-producing isolates originated from the Greater Accra Region (55.4%). At the facility level, ESBL producers were most prevalent at KBTH (16.2%), followed by GARH (14.9%), 37 MH (13.5%), PMLCH (8.1%), Private Lab (1.4%), and LEKMA Hospital (1.4%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). ESBL-producing isolates demonstrated high resistance rates (often\u0026thinsp;\u0026gt;\u0026thinsp;60%) to most antibiotics tested, including ampicillin, trimethoprim-sulfamethoxazole, ceftriaxone, gentamicin, cefotaxime, ceftazidime, tetracycline, azithromycin, ciprofloxacin, and chloramphenicol (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA). All ESBL-producing isolates (74/74; 100%) were MDR, compared with 76.2% (16/21) of non-ESBL-producing isolates. The majority of the isolates remained susceptible to meropenem and ertapenem. Detailed antimicrobial susceptibility and phenotypic test results are presented in supplementary table S1.\u003c/p\u003e \u003cp\u003eOf the 91 isolates tested for AmpC production, 51.6% (47/91) were confirmed as AmpC-producers. Among these, 27.7% were recovered from females and 25.5% from males, while sex data were missing for 46.8% of isolates. The proportion of AmpC-producing \u003cem\u003eK. pneumoniae\u003c/em\u003e was relatively higher among children under five years of age compared with individuals aged 5\u0026ndash;19 years and adults older than 60 years (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Most AmpC-producing isolates originated from the Greater Accra Region (40.4%). At the facility level, AmpC-producers were most prevalent at KBTH (25.5%), followed by GARH (10.6%), PMLCH (2.1%), and 37 MH (2.1%). No AmpC-producing isolates were recorded from LEKMA Hospital or the Private Lab (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). AmpC producing isolates demonstrated high resistance rates (\u0026gt;\u0026thinsp;60%) to most antibiotics tested, whereas non-AmpC producers exhibited moderate to high resistance across the antibiotics evaluated (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB). With the exception of one isolate, all AmpC producers (97.9%; 46/47) were MDR. Among non-AmpC producers, 90.9% (40/44) were MDR.\u003c/p\u003e \u003cp\u003eCarbapenemase testing was performed on 64 isolates (due to resource constraints), of which 26.6% were confirmed as carbapenemase-producers. Among these, 29.4% were recovered from females and 17.6% from males, while sex data were missing for 52.9% of isolates. There was no statistically significant difference in carbapenemase-producing \u003cem\u003eK. pneumoniae\u003c/em\u003e across the different age groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Most carbapenemase-producing isolates originated from the Greater Accra Region (41.2%). At the facility level, carbapenemase producers were most prevalent at KBTH (35.3%), followed by 37 MH (5.9%). However, none were recorded from GARH, PMLCH, Private Lab, and LEKMA (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Generally, carbapenemase producers demonstrated high resistance to the various antibiotics, while non-carbapenemase producers showed slightly high resistance to the antibiotics (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC). With the exception of one isolate, 94.1% (16/17) of carbapenemase producers were MDR. Similarly, 97.9% (46/47) of non-carbapenemase producers were MDR.\u003c/p\u003e \u003cp\u003eColistin susceptibility testing was performed on 48 isolates (due to resource constraints), of which 12.5% were confirmed as colistin-resistant. Among these, 50.0% were recovered from females, 33.3% from males, and sex data were missing for 16.7% of isolates. The proportion of colistin-resistant \u003cem\u003eK. pneumoniae\u003c/em\u003e was similar among children under five and other age groups (5\u0026ndash;19 years), with no statistically significant difference observed (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.272) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). No colistin-resistant isolates were identified from the Greater Accra Region. Colistin-resistant isolates exhibited very high resistance to most antibiotics tested, whereas colistin-susceptible isolates showed moderately high resistance across the same antibiotics. Although all colistin-resistant isolates (6/6; 100%) were MDR, they remained susceptible to meropenem and ertapenem (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD). Among colistin-susceptible isolates, 97.6% (40/41) were MDR.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study investigated the prevalence of antibiotic resistance and β-lactam-degrading enzymes specifically ESBLs, AmpCs, and carbapenemases among \u003cem\u003eK. pneumoniae\u003c/em\u003e isolates recovered from blood cultures in Southern Ghana. A high prevalence of resistance was observed across nearly all antibiotics tested, except for meropenem and ertapenem, aligning with previous findings from Ghana,\u003csup\u003e34,35\u003c/sup\u003e and other regions.\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e Resistance to third-generation cephalosporins, including cefotaxime, ceftazidime, and ceftriaxone, is often linked to ESBL production.\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e Consequently, even if an isolate appears susceptible \u003cem\u003ein vitro\u003c/em\u003e, treatment failure may occur if it harbors ESBL genes\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe high resistance rate to gentamicin, an aminoglycoside, observed in this study may be attributed to several mechanisms, including: (1) enzymatic inactivation by aminoglycoside-modifying enzymes such as acetyltransferases, nucleotidyltransferases, or phosphotransferases; (2) increased efflux; (3) reduced permeability; and (4) alterations in the 30S ribosomal subunit that prevent drug binding\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e. This is especially concerning given the widespread and often empiric use of aminoglycosides in Ghana, where they are among the most commonly prescribed antibiotics\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e,\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e. A six-year review at a Ghanaian secondary healthcare facility found gentamicin usage at a rate of 13.1 defined daily doses per 100 patients, with no significant reduction from 2016 to 2021\u003csup\u003e43\u003c/sup\u003e. The overuse and misuse of antibiotics particularly aminoglycosides, cephalosporins, and fluoroquinolones is a key driver of AMR and highlight the urgent need for stricter prescribing practices and improved surveillance.\u003c/p\u003e \u003cp\u003eIn contrast, meropenem and ertapenem retained relatively high effectiveness against MDR strains, consistent with reports from other settings.\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e Their limited use is likely attributable to their high cost, intravenous administration, and their designation as last-resort agents in national treatment guidelines. Although these carbapenems have been available in Ghana since 2002, their lower consumption compared with older antibiotics such as aminoglycosides, may have contributed to the preservation of their efficacy. Nevertheless, judicious use remains essential, and routine monitoring of carbapenem use should be emphasized as a key component of antimicrobial stewardship programs.\u003c/p\u003e \u003cp\u003eThe prevalence of ESBL production in this study (77.9%) was significantly higher than previous reports from China (12.1%)\u003csup\u003e46\u003c/sup\u003e, Italy (30%)\u003csup\u003e45\u003c/sup\u003e, and sub-Saharan Africa (45.5%)\u003csup\u003e47\u003c/sup\u003e. The elevated rate may reflect long-standing but under-recognized community circulation of ESBL-producing strains in Ghana, exacerbated by limited laboratory capacity and lack of awareness\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. The prevalence reported here is comparable to studies in Egypt (76.2%)\u003csup\u003e48\u003c/sup\u003e, and Ghana (71.2%)\u003csup\u003e49\u003c/sup\u003e, (75.6%)\u003csup\u003e50\u003c/sup\u003e, though lower than figures from Bangladesh (80%)\u003csup\u003e24\u003c/sup\u003e, Belgium (89.3%)\u003csup\u003e51\u003c/sup\u003e, Egypt (80%)\u003csup\u003e52\u003c/sup\u003e, and C\u0026ocirc;te d\u0026rsquo;Ivoire\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Variations in ESBL prevalence likely stem from geographic, methodological, and temporal differences. ESBL prevalence was notably higher among children under five, though not statistically significant (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.933), likely due to increased empirical antibiotic use in this age group.\u003c/p\u003e \u003cp\u003eMDR is strongly associated with ESBL production, and the high prevalence of MDR \u003cem\u003eK. pneumoniae\u003c/em\u003e observed especially among ESBL producers is consistent with earlier findings from Ghana\u003csup\u003e\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e,\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e, and other regions\u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e,\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u003c/sup\u003e. Resistance was particularly high for penicillins, trimethoprim-sulfonamide combinations, aminoglycosides, third-generation cephalosporins, tetracyclines, macrolides, and fluoroquinolones. This is alarming, as these antibiotics are frequently used empirically for syndromic treatment\u003csup\u003e\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e\u003c/sup\u003e. The increasing ineffectiveness of these drugs against MDR pathogens necessitates urgent, multifaceted public health interventions, including enhanced diagnostics, refined treatment protocols, and robust infection control measures.\u003c/p\u003e \u003cp\u003eAmpC production was detected in 51.6% of isolates significantly higher than previous reports from Saudi Arabia (5.5%)\u003csup\u003e58\u003c/sup\u003e, Libya (6.7%)\u003csup\u003e59\u003c/sup\u003e, and Ghana (19.4%)\u003csup\u003e49\u003c/sup\u003e, (17%)\u003csup\u003e60\u003c/sup\u003e, but comparable to a study from Iran (52.9%)\u003csup\u003e61\u003c/sup\u003e. AmpC prevalence remains underdefined in sub-Saharan Africa due to the absence of rapid, validated detection methods\u003csup\u003e\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e\u003c/sup\u003e. Consequently, its burden may be underestimated, underscoring the need to develop and implement standardized detection protocols\u003csup\u003e\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCarbapenemase production was detected in 26.6% of isolates \u0026ndash; significantly higher than previously reported rates in Ghana: 5.6% by Dwomoh et al.\u003csup\u003e53\u003c/sup\u003e, 2.9% by Codjoe et al.\u003csup\u003e63\u003c/sup\u003e, and 7.2% by Hackman et al.\u003csup\u003e64\u003c/sup\u003e. The present study\u0026rsquo;s focus on \u003cem\u003eK. pneumoniae\u003c/em\u003e from blood cultures in secondary and tertiary hospitals in Southern Ghana may account for this higher prevalence. The findings align with a recent Ghanaian study reporting 26.4% prevalence\u003csup\u003e49\u003c/sup\u003e, and with similar findings from Uganda\u003csup\u003e\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e\u003c/sup\u003e, though still lower than those from Egypt (54.1%)\u003csup\u003e66\u003c/sup\u003e. Elsewhere, reported carbapenemase rates vary 4.9% in Argentina\u003csup\u003e\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e\u003c/sup\u003e, 5.74% in Malaysia\u003csup\u003e\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e\u003c/sup\u003e, and 9.1% in Nepal\u003csup\u003e\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e\u003c/sup\u003e, but collectively point to a global rise in carbapenem resistance, requiring urgent, coordinated responses.\u003c/p\u003e \u003cp\u003eColistin resistance was identified in 12.5% of isolates comparable to rates from Kuwait (12.0%)\u003csup\u003e37\u003c/sup\u003e, and Spain (13.1)\u003csup\u003e55\u003c/sup\u003e, but lower than those reported in India (33.3%)\u003csup\u003e14\u003c/sup\u003e, Italy (43%)\u003csup\u003e56\u003c/sup\u003e, and Ghana (57%)\u003csup\u003e22\u003c/sup\u003e. These variations may reflect differences in antibiotic use practices, population demographics, resistance trends, and detection methods. The absence of standardized, rapid colistin resistance testing and lack of consistent antimicrobial use guidelines compounded by limited public awareness remains a challenge, especially given colistin\u0026rsquo;s role as a last-resort antibiotic for MDR Gram-negative infections. Many healthcare facilities in resource-limited settings lack the diagnostic capacity to detect colistin resistance\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e, leading to its underreporting. Although the prevalence found here is relatively low, regular nationwide surveillance is essential.\u003c/p\u003e \u003cp\u003eThis study has certain limitations. Archived isolates were used, limiting access to detailed clinical data such as underlying conditions or comorbidities. Nonetheless, inclusion of isolates from both secondary and tertiary care facilities across Southern Ghana enhances the study\u0026rsquo;s representativeness and generalizability.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study reveals a high prevalence of ESBL, AmpC, carbapenemase production, and colistin resistance among \u003cem\u003eK. pneumoniae\u003c/em\u003e isolates from blood cultures in Southern Ghana. Notably, a subset of isolates harbored all three β-lactamase enzymes and were concurrently resistant to colistin, presenting a significant therapeutic challenge.\u003c/p\u003e \u003cp\u003eRoutine detection and characterization of resistance mechanisms, coupled with robust laboratory surveillance, are urgently needed to guide effective clinical management and containment strategies. The responsible use of last-resort antibiotics such as meropenem and ertapenem must be prioritized, while the overuse of third-generation cephalosporins, aminoglycosides, and fluoroquinolones should be strictly regulated.\u003c/p\u003e \u003cp\u003eThe widespread presence of MDR \u003cem\u003eK. pneumoniae\u003c/em\u003e in both ESBL-producing and non-ESBL-producing isolates, as well as AmpC-producing and non-AmpC-producing isolates, and carbapenemase-producing and non-carbapenemase-producing isolates underscores the urgent need to enhance infection-prevention and control measures. Strengthening antimicrobial stewardship programs within both healthcare facilities and communities is essential to curb the spread of resistance and preserve the efficacy of available antibiotics.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are highly grateful to all staff of the Microbiology Departments in all nine sentinel sites, all staff of the Department of Medical Microbiology, College of Health Sciences, Korle-Bu, especially Joseph Anamsi, Grace Semevor, Rita Serwaa Addo, Ursela Serwaa Sarfo, and Isaura Namen-Arikum Yelkebono for their enormous technical support during the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: FKMT, WB, KOD, and ES-D. Methodology: FKMT, MMO, FCNK, BD, and KOD. Validation: FKMT, MMO, FCNK, BD, KOD, and ES-D. Formal analysis: FKMT, WB, BD, and KOD. Investigation: FKMT. Data curation: FKMT, WB, MMO, FCNK, and BD. Writing - original draft preparation: FKMT. Writing - review and editing: FKMT, WB, KOD, and ES-D. Visualization: FKMT, WB, MMO, FCNK, BD, KOD, and ES-D. Supervision: KOD, and ES-D. Resources: FKMT, MMO, FCNK, and ES-D. Project administration: FKMT, MMO, FCNK, and ES-D. All authors reviewed final draft of the manuscript and approved for submission.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during the study are included in this article. Further inquiries can be directed to the corresponding authors.\u003c/p\u003e\n\u003cp id=\"_Toc214299715\"\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Ethical and Protocol Review Committee (EPRC) of the College of Health Sciences, University of Ghana, approved the research study (protocol identification number: CHS-Et/M.2-P4.6/2021-2022). Approval was also obtained from the respective study sites. Informed consent was waived by the ethics committee because there was no contact with patients. Archived bacterial isolates were retrieved and used. The isolates had been de-identified prior to retrieval. All methods were performed in accordance with the relevant standard guidelines and regulations. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFKMT was supported with a Doctoral Fellowship Award \u0026ldquo;ST/PhD/004/2022\u0026rdquo; from the West Africa Genomic Medicine Centre (WAGMC), University of Ghana. The views expressed in this publication are those of the authors and not necessarily those of the University of Ghana or the WAGMC.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOlalekan A et al (2020) High proportion of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae among extended-spectrum β-lactamase-producers in Nigerian hospitals. 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Infect Drug Resist 13:2311\u0026ndash;2321\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"University of Ghana","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Klebsiella pneumoniae, Extended-spectrum beta-lactamase, AmpC, Carbapenemase, Colistin","lastPublishedDoi":"10.21203/rs.3.rs-9086605/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9086605/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAntibiotic-resistant \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e presents a significant global health threat, prompting urgent calls for new treatment options. This study determined antibiotic resistance profiles of \u003cem\u003eK. pneumoniae\u003c/em\u003e isolates from blood cultures in Southern Ghana and characterized the β-lactamase enzymes mediating β-lactam resistance. Archived \u003cem\u003eK. pneumoniae\u003c/em\u003e isolates stored at -80\u0026deg;C at the Department of Medical Microbiology, University of Ghana Medical School were retrieved and revived for the study. Isolate identities were confirmed using the BD Bruker MALDI-TOF. Antimicrobial susceptibility testing was performed using both the MicroScan AutoSCAN system and Kirby-Bauer disc diffusion method. Of the 109 non-duplicate archived isolates, 95 (87.2%) were confirmed as \u003cem\u003eK. pneumoniae\u003c/em\u003e. All confirmed isolates exhibited resistance to at least one antibiotic class, with two isolates (2.1%) resistant to all tested antibiotics. High resistance rates were observed for trimethoprim-sulfamethoxazole (85.3%), gentamicin (83.2%), ceftriaxone (80.0%), cefotaxime (78.9%), and ceftazidime (77.9%). Resistance to ertapenem (18.9%), and meropenem (8.4%) was comparatively lower. β-Lactamase enzyme profiles revealed that 77.9% (n\u0026thinsp;=\u0026thinsp;74/95) of screened isolates were extended-spectrum beta-lactamase (ESBL) producers, 51.6% (n\u0026thinsp;=\u0026thinsp;47/91) were AmpC producers, 26.6% (n\u0026thinsp;=\u0026thinsp;17/64) were carbapenemase-producers, and 12.5% (n\u0026thinsp;=\u0026thinsp;6/48) exhibited resistance to colistin. Notably, 12.5% of isolates concurrently produced ESBL, AmpC, and carbapenemase enzymes and were resistant to colistin. The prevalence of ESBL-producing \u003cem\u003eK. pneumoniae\u003c/em\u003e was higher among children under five years of age compared to adults over sixty, though the difference was not statistically significant (\u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.933). All ESBL-producing isolates were multidrug-resistant (MDR), and 76.2% (n\u0026thinsp;=\u0026thinsp;21) of non-ESBL producers were also MDR. AmpC-producing isolates were significantly more prevalent among children under five than among those aged 5\u0026ndash;19 and adults over sixty (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.023). The high prevalence of MDR \u003cem\u003eK. pneumoniae\u003c/em\u003e strains producing ESBLs, AmpCs, carbapenemases, and exhibiting colistin resistance is alarming and significantly narrows treatment options for bloodstream infections. These findings highlight the urgent need for alternative therapeutic strategies and routine surveillance to guide effective clinical management and antimicrobial stewardship.\u003c/p\u003e","manuscriptTitle":"Antibiotic resistance and occurrence of extended-spectrum beta-lactamases, AmpC and carbapenemases in Klebsiella pneumoniae from blood cultures in Southern Ghana","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-12 11:52:59","doi":"10.21203/rs.3.rs-9086605/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cb82cd74-5920-4540-9b93-0483c717f864","owner":[],"postedDate":"March 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":64273302,"name":"Bacteriology"},{"id":64273303,"name":"Infectious Diseases"},{"id":64273304,"name":"Laboratory Diagnostics"}],"tags":[],"updatedAt":"2026-03-12T11:52:59+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-12 11:52:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9086605","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9086605","identity":"rs-9086605","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}