First Comparative Evaluation of Omadacycline, Tigecycline, and Eravacycline Against Carbapenem-Resistant Acinetobacter baumannii and Klebsiella pneumoniae in Beijing Tertiary Teaching Hospital: An in Vitro Broth Microdilution Study

First Comparative Evaluation of Omadacycline, Tigecycline, and Eravacycline Against Carbapenem-Resistant Acinetobacter baumannii and Klebsiella pneumoniae in Beijing Tertiary Teaching Hospital: An in Vitro Broth Microdilution Study | 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 Article First Comparative Evaluation of Omadacycline, Tigecycline, and Eravacycline Against Carbapenem-Resistant Acinetobacter baumannii and Klebsiella pneumoniae in Beijing Tertiary Teaching Hospital: An in Vitro Broth Microdilution Study Diandian CHEN, He LAN, Wenshuo YANG, Dequan TIAN, Yunyi LIU, Leyang JU, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7052797/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 The rising prevalence of carbapenem-resistant organisms (CROs) necessitates the exploration of novel therapeutics options. This study evaluated the in vitro activity and clinical outcomes of three tetracycline-class antibiotics—Eravacycline (ERV), Tigecycline (TGC), and Omadacycline (OMC)—against regional CRO isolates. A total of 233 non-duplicate clinical CRO isolates (106 carbapenem-resistant Klebsiella pneumoniae [CRKP] and 117 carbapenem-resistant Acinetobacter baumannii [CRAB]) were collected from Xuanwu Hospital in 2024. Antimicrobial susceptibility was determined via broth microdilution to measure minimum inhibitory concentrations (MIC), complemented by 0–48 hour time-kill assays. Clinical outcomes of patients treated with TGC or ERV were analyzed. Key findings included: 1. Antimicrobial Potency : ERV demonstrated superior in vitro activity, with MIC 90 values of 0.5 mg/L (ERV), 2 mg/L (TGC), and 4 mg/L (OMC)—4-fold lower than TGC and 8-fold lower than OMC. 2. Time-kill Assays : ERV achieved sustained bactericidal activity at 4–8 × MIC (a novel observation), particularly against CRAB, maintaining >3-log₁₀ CFU/mL reduction for 24–36 hours—2.3-fold longer than TGC and 3.1-fold longer than OMC. While effective against CRKP, ERV demonstrated pathogen-specific advantages for CRAB. 3. Clinical Correlation : The ERV-treated cohort (n = 4) exhibited 0% mortality, compared to TGC-treated patients with 18.9% mortality for CRAB (7/37) and 16.7% for CRKP (4/24). ERV displayed enhanced bactericidal activity and lower resistance thresholds compared to TGC. Preliminary clinical data support its potential as a core therapeutic agent for CRO infections, warranting futher validation in multicenter studies. Health sciences/Diseases Health sciences/Medical research Biological sciences/Microbiology Carbapenem-Resistant Acinetobacter baumannii Carbapenem-Resistant Klebsiella pneumoniae Broth microdilution method Time-kill assays tetracycline-class antibiotics Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction The global dissemination of carbapenem-resistant Gram-negative organisms (CROs) represents a critical public health threat. Surveillance data from China’s CHINET consortium (2024) indicate alarmingly high detection rates: 26.4% for carbapenem-resistant Klebsiella pneumoniae (CRKP) and 66.5% for carbapenem-resistant Acinetobacter baumannii (CRAB), with even higher prevalence observed in intensive care unit (ICU) patients (CRAB: 78.3%) 1,2 . These pathogens employ diverse resistance mechanisms, primarily mediated by carbapenemase-encoding genes: KPC (Class A serine β-lactamases, dominant in 62% of CRKP isolates); NDM (Class B metallo-β-lactamases, common in E. coli ); and OXA-48 (Class D oxacillinases, prevalent in K. pneumoniae ) 3 . These multidrug-resistant (MDR) phenotypes contribute to high 30-day mortality rates (35% for CRKP and 48% for CRAB infections), attributed to the failure of conventional therapitic options 4,5 . Moreover, transmission of these resistant pathogens within healthcare facilities exacerbates clinical management challenges, as they disseminated through multiple pathways: interpatient contact, contaminated medical devices, and environmental reservoirs. The global proliferation of such high-level resistant organisms underscores the urgent need to develop novel therapeutic strategies and enhanced infection control protocols to mitigate their clinical impact. Current guidelines endorse Eravacycline and Tigecycline as alternative therapeutic options for CRKP and CRAB infections. Tigecycline remains the more widely utilized agent owing to its earlier clinical implementation but exhibits notable limitations: suboptimal serum concentrations, limited alveolar penetration (one-third of serum levels), and elevated coagulation risks associated with high-dose regimens 6 . In contrast, Eravacycline demonstrates superior concentrations in alveolar epithelial lining fluid (8-fold higher than serum levels) and a reduced incidence of coagulation disorders. Nevertheless, its classification as an "alternative agent" persists due to limited Phase III clinical evidence—particularly for pulmonary and bloodstream infections, where its pharmacodynamic profile indicates substantial therapeutic potential 7 . Omadacycline, another next-generation tetracycline, is recommended for treating community-acquired pneumonia owing to its high oral bioavailability. This study constitutes the first tertiary teaching hospital-based comparative analysis of in vitro susceptibility profiles of ERV, TGC, and OMC against clinical CRKP and CRAB isolates. For CRKP, the current core agent ceftazidime/avibactam was further included in the comparative analysis. These findings provide critical evidence supporting ERV as a potential core antimicrobial agent. Materials and methods Clinical isolates A total of 106 non-duplicate CRKP and 117 CRAB isolates were collected from Xuanwu Hospital of Capital Medical University, from January and December 2024. All strains were cryopreserved at -80°C in 15%–20% glycerol broth prior to recovery. Species identification was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry ( Bruker Daltonics, Germany) following strain revitalization. Genotyping The carbapenemase genotypes of CRKP isolates were determied using immunochromatographic colloidal gold assays (Beijing Jinshanchuan Technology Development Co., Ltd.), with further confirmation via real-time PCR (Ningbo Jinei Biotechnology Co., Ltd.) specifically for isolates exhibiting multi-genotype co-carriage 8 . Colloidal gold immunoassay procedure and result interpretation: (1) Sample preparation: Suspend a pure bacterial colony in the supplied extraction buffer, vortex vigorously for 30–60 seconds, and allow coarse particles to settle. (2) Assay execution: Transfer the clarified supernatant into the sample well of the test device. (3) Result reading: Interpret results within 5–15 minutes post-assay: Positive, both the test line (T) and control line (C) are clearly visible; Negative, no visible test line (T) is observed, but the control line (C) remains visible; Invalid, no visible control line (C) is detected, regardless of the presence of a T line (repeat the test). The RT-PCR detection of antibiotic resistance genes encompasses the following critical steps: Firstly, genomic DNA is extracted from bacterial samples. Subsequently, target sequences are amplified using gene-specific primers and a fluorescent probe within a real-time PCR thermal cycler. A positive result is denoted when fluorescence exceeds the threshold value within the predefined cycle limit (Ct ≤ 37), whereas the absence of significant increase in fluorescence across the cutoff cycle threshold signifies a negative result. Importantly, the valid interpretation of results requires the successful execution of positive and negative controls, as well as internal extraction controls. Antimicrobial susceptibility test (AST) Minimum inhibitory concentrations (MIC) for TGC, ERV, and OMC were determined using the broth microdilution method in accordance with CLSI M07 guidelines [13] . Positive controls comprised CRKP strains resistant to all three antibiotics (verified via E-test), whereas E. coli ATCC25922 served as the negative control. Assays were conducted in 96-well plates: antibiotics were initially dissolved, serially diluted to a stock concentration of 2560 μg/mL, aliquoted, and cryopreserved prior to use. The microbroth doubling dilution method was applied during testing, with final antibiotics concentrations ranging from 32 to 0.064 μg/mL. MIC interpretation followed: Food and Drug Administration (FDA) breakpoints for TGC (≤ 2 μg/mL [susceptible, S], 4 μg/mL [intermediate, I], ≥ 8 μg/mL [resistant, R]) and OMC (≤ 4 μg/mL [S], 8 μg/mL [I], ≥ 16 μg/mL [R]) 9 . ChinaCAST breakpoints for ERV (≤ 1 μg/mL [S]) 10 . Notably, CLSI and EUCAST breakpoints generally aligned with FDA criteria, with the exception of EUCAST’s revised TGC breakpoint (≤ 0.5 μg/mL [S] specifically for K. pneumoniae ) 11 . Time-kill Assays Five strains with known MICs ( bla NDM : 0.5 μg/mL, bla NDM + bla KPC : 0.5 μg/mL, bla NDM + bla KPC + bla OXA-48 : 0.125 μg/mL, bla KPC : 0.25 μg/mL, and CRAB: 1 μg/mL) were selected. Bactericidal activity was evaluated at their respective MIC concentrations using a 96-well plate. Antimicrobial susceptibility test (AST) was performed via the microbroth dilution method in accordance with CLSI M07-A13. Bacterial growth was monitored by measuring OD600 absorbance (0–24 hours, hourly; 24–48 hours, every 2 hours; > 48 hours, every 6 hours). Standard curves derived from negative controls were used to calculate log 10 CFU/mL 12 . Clinical Efficacy Analysis Demographic data, combination therapies, and case fatality rates were collected for 223 CRO-infected patients treated with TGC or ERV; OMC was unavailable for this study. Efficacy was evaluated within the predefined MIC ranges. This study adheres to the principles of the Declaration of Helsinki and institutional regulations of Xuanwu Hospital, Capital Medical University. The research protocol was approved by the Medical Ethics Committee of Xuanwu Hospital, Capital Medical University (Clinical Research Approval No.: XA[KS2024]039-002). All patients provided written informed consent upon admission, as detailed in the supplementary materials. Statistical Analysis Results were compiled in Microsoft Excel and statistical analyses were performed using SPSS 26.0. Categorical variables were presented as percentages [n (%)] and analyzed using the chi-square (χ²) test. Statistical significance was defined as a two-tailed p-value < 0.05. Results Clinical Isolates Distribution CRKP and CRAB were most frequently isolated from sputum (57.8% vs. 63.7%) and bronchoalveolar lavage fluid (8.4% vs. 8.5%), followed by blood (9.4% vs. 5.1%), urine (16.0% vs. 8.5%), and drainage fluid (8.4% vs. 5.1%) (Figure 1). Antimicrobial Susceptibility Test (AST) CRKP (n = 106): Susceptibility rates were 94% for ERV, 77% for TGC, and 17% for OMC. MIC 50 /MIC 90 values were 0.5/1 μg/mL for ERV, 2/4 μg/mL for TGC, and 16/32 μg/mL for OMC. CRAB (n = 117): All isolates exhibited susceptibility to TGC and OMC, with 99.1% susceptibility to ERV. MIC 50 /MIC 90 values were 0.125/0.25 μg/mL for ERV, 0.5/1 μg/mL for TGC, and 1/2 μg/mL for OMC. OMC demonstrated species-dependent activity, with an 8-fold lower MIC 90 against CRAB compared to CRKP (8 vs. 64 μg/mL), outperformed TGC with 4-fold lower MIC 90 values than ERV against both species (Table 1). Statistical comparisons (χ² test) revealed that ERV exhibited significantly higher susceptibility rates than TGC (EUCAST: χ² = 28.41, p < 0.001; FDA: χ² =9.56, p = 0.002), OMC (FDA: χ² = 34.17, p < 0.001), and ceftazidime/avibactam (CLSI: χ² = 4.92, p = 0.027) for CRKP. Subgroup analysis based on carbapenemase type confirmed the superiority of ERV in KPC-producing and metallo-β-lactamase (MBL)-producing CRKP (Figure 2). No significant differences in susceptibility rates were observed for CRAB. Subgroup Analysis by Carbapenemase Type KPC-producing CRKP: ERV exhibited a significantly higher susceptibility rate (94%) than TGC (EUCAST breakpoints ≤ 0.5 mg/L: 52.1%, χ² = 31.09, p < 0.001; FDA breakpoints ≤ 2 mg/L: 77%, χ² = 10.24, p = 0.001). ERV also showed significantly higher susceptibility than OMC (17%, FDA breakpoints ≤ 4 mg/L: χ² = 72.35, p < 0.001). Metallo-β-lactamase (MBL)-producing CRKP: ERV demonstrated significantly superior activity compared to OMC (FDA breakpoints ≤ 4 mg/L: χ² = 19.83, p < 0.001) and TGC (EUCAST breakpoints ≤ 0.5 mg/L: χ² = 8.94, p = 0.003). Additionally, ERV demonstrated significantly higher activity compared to ceftazidime-avibactam (CLSI breakpoints ≤ 8/4 mg/L: χ² = 7.01, p = 0.008). Time-kill Assays Both CRAB and CRKP carbapenemase-producing strains showed robust antibacterial activity compared to positive controls, with bacteriostatic effects lasting up to 12 hours. The bacteriostatic efficacy of CRAB was superior to that of CRKP. Among CRKP strains, MBL showed stronger performance than KPC carbapenemase. ERV maintained sustained bactericidal activity (≥ 3-log 10 reduction) for 24–36 hours against CRAB and 12–24 hours against CRKP, outperforming TGC and OMC, which exhibited bacterial regrowth post-12 hours (Figure 4). Clinical Outcomes We analyzed 223 CRO isolates exposed to the targeted antibiotics. A total of 36 CRAB isolates were collected from patients (26 males, 10 females; age range 27–93 years), with department distribution as follows: Neurology ICU (n = 13), Critical Care ICU (n = 9), Respiratory ICU (n = 5), General Surgery ICU (n = 4), Neurosurgery ICU (n = 2), and Rehabilitation Department (n = 3); ICU patients accounted for 91.7% (33/36) of these cases. Similarly, 24 CRKP isolates were obtained from patients (21 males, 3 females; age range 17–92 years), distributed across departments: General Surgery ICU (n = 6), Critical Care ICU (n = 5), Neurosurgery ICU (n = 4), Neurology ICU (n = 3), Respiratory ICU (n= 2), Emergency ICU (n = 2), Hematology Department (n = 1), and General Medicine Department (n = 1); ICU patients also represented 91.7% (22/24) of the CRKP cases. Among the TGC-treated patients (n= 60; 36 CRAB, 24 CRKP), mortality rates were 19.4% (7/36) for CRAB infections and 16.7% (4/24) for CRKP infections. ERV-treated patients (n= 4; 3 CRAB and 1 CRKP) exhibited a mortality rate of 0% (Table 3). Discussion This study presents the first comprehensive in vitro and clinical evaluation of three tetracycline-class agents against 223 CRO isolates. Key findings are as follows: (a) MIC profiles: ERV demonstrated 4-fold lower MIC values than TGC and 8-fold lower than OMC; (b) Bactericidal superiority: ERV exhibited prolonged bactericidal activity, particularly against CRAB; (c) Clinical correlation: TGC showed suboptimal clinical outcomes, whereas ERV achieved 100% survival in a limited number of cases. CRKP and CRAB were most prevalent in respiratory samples (sputum and bronchoalveolar lavage fluid), highlighting respiratory tract infections as a major clinical burden. Their detection in blood, urine, and cerebrospinal fluid further underscores the need for vigilance in managing bloodstream, urinary, and central nervous system infections. The escalating prevalence of CRKP and CRAB in clinical isolates has emerged as a critical challenge for contemporary antimicrobial stewardship 13,14 . This study utilized the CLSI-standardized broth microdilution method (M07-A11) to evaluate the in vitro efficacy of three tetracycline-class agents—ERV, OMC, and TGC—against 106 CRKP and 117 CRAB isolates. For CRKP, ERV (94% susceptibility rate) outperformed TGC (77%) and OMC (17%). Application of EUCAST's revised TGC breakpoints (≤0.5 μg/mL) reduced TGC susceptibility to 52.1%, highlighting the impact of breakpoints interpretation variability. For CRAB, all three agents showed comparable activity (ERV: 99.1%, TGC/OMC: 100%), though EUCAST's lack of Acinetobacter-specific breakpoints complicates global comparisons. Eravacycline, a broad-spectrum tetracycline-class antibiotic, exhibits activity against most of MDR bacteria, including CRAB, CRE, Methicillin-Resistant Staphylococcus aureus (MRSA), and Vancomycin-resistant Enterococci (VRE). Its enhanced activity is attributed to its reduced efflux pump affinity (50-fold lower than TGC for AcrAB-TolC/MexAB-OprM systems) and lower MICs (8–32-fold) against TetM/O-mediated resistance 15,16 . Superior tissue penetration (8-fold higher alveolar fluid concentration) supports potential utility in pulmonary infections 17 . Notably, this study detected ERV-resistant CRKP and CRAB strains, consistent with international reports 18 . Distinct mechanisms underlie Omadacycline resistance in CRKP and CRAB. In CRKP isolates, elevated MICs correlated with overexpression of AcrAB-TolC efflux pump genes 19 , whereas CRAB strains demonstrated lower MICs associated with OprD porin protein deficiency 20 . Omadacycline activity was species-dependent, with an 8-fold lower MIC 90 against CRAB than CRKP—likely reflecting efflux pump overexpression in CRKP versus porin deficiency in CRAB. The susceptibility rate of CRKP to Omadacycline was 17%, with approximately 50% resistance observed across strains carrying KPC, NDM, or both carbapenemase genes. Interestingly, two isolates co-harboring KPC, NDM, and OXA-48 genes showed no resistance (one susceptible, one intermediate). This aligns with emerging evidence of Omadacycline activity against OXA-48-producing CRKP. However, our study was limited by small OXA-48 carriers numbers(n = 2) and absence of OXA-48-exclusive isolates, highlighting the need for targeted collection of OXA-48-producing strains to elucidate underlying mechanisms 21 . Notably, OMC demonstrates unique pharmacokinetic advantages over other tetracycline-class agents (ERV and TGC). Its oral bioavailability supports utility in mild-to-moderate community-acquired infections 22 . These findings underscore the need for continued surveillance of resistance mechanisms and genotype-phenotype correlations to optimize OMC utilization in antimicrobial stewardship programs. Further analysis revealed sustained bactericidal activity of ERV throughout the 36-hour observation period, maintaining effective bacterial suppression. In contrast, despite robust initial bactericidal effects, OMC and TGC showed increased bactericidal loads after 12 hours, indicating potential resistance development or time-dependent efficacy reduction. Notably, ERV exerted concentration-dependent bactericidal effects against both CRAB and CRKP, with higher concentrations correlating to prolonged and enhanced antibacterial activity. At concentrations of 4–8 × MIC, ERV completely suppressed bacterial regrowth over 0–36 hours—a effect not observed with TGC or OMC at 2 × MIC in time-kill assays. Comparative analysis of MIC values revealed that ERV achieved bactericidal activity at significantly lower concentrations than TGC or OMC. Critically, published pharmacokinetic studies demonstrate superior tissue penetration of ERV 23 , particularly in alveolar epithelial lining fluid (ELF) and serum, with concentrations exceeding those of TGC by 2.3-fold and OMC by 3.1-fold, respectively. This pharmacokinetic-pharmacodynamic (PK/PD) profile positions ERV as the most viable candidate for attaining clinically effective bactericidal levels in vivo . These findings highlight the potential of ERV as a therapeutic option for infections caused by MDR pathogens, particularly in clinical settings where sustained bactericidal activity is crucial for optimizing patient outcomes. Limitations of this study include its single-center design, small sample size of ERV-treated cohort, and therapeutic imbalance (predominance of TGC treatment). Further multi-center studies with balanced treatment arms are warranted to validate the clinical efficacy of ERV. Conclusion Eravacycline demonstrated broad-spectrum activity and superior bactericidal efficacy against CRKP and CRAB, supported by favorable pharmacokinetics properties. However, its potential as a first-line agent for CRO infections requires further clinical validation. Omadacycline demonstrates species-specific advantages (notably against CRAB) and oral administration utility, while Tigecycline's limitations—including suboptimal tissue penetration and elevated adverse event rates—restrict its role in CRO management. Declarations Ethical standards The research protocol was approved by the Medical Ethics Committee of Xuanwu Hospital of Capital Medical University (Approval Number: XA[KS2024] 039-002). All methods were carried out in accordance with relevant guidelines and regulations Data availability The datasets generated and analyzed during the current study are not publicly available due to the ethical limiting data use to this study. However, a data-sharing protocol will be established in consultation with the hospital for researchers with legitimate requests. The original data files that meet ethical requirements have been uploaded in the supplementary materials section. Raw data supporting the conclusions are available from the corresponding author (JR CAO) upon reasonable request. Funding The author (s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by Hebei Provincial Department of Science and Technology (Grant/Award Number: 244X7703D & XA202401102002K), Beijing Municipal Health Commission (Funding number: Discipline Backbone-01-023) and Beijing Natural Science Foundation (Funding number: L256081). Acknowledgments All isolates and demographic data for this study were provided by Xuanwu Hospital of Capital Medical University. We extend our sincere gratitude to all study participants who contributed samples. Additionally, the research team acknowledges the invaluable dedication of participants who generously donated their time and effort to support this investigation. Author contributions Diandian CHEN, He LAN, and Wenshuo YANG contributed to the study concept and design, data curation, methodology, drafted the manuscript. Dequan TIAN, Yunyi LIU, Rong MIN, Yan WANG, Ying LI, Leyang JU and Qiao SONG contributed to the acquisition of data, data processing, statistical analysis, and reagents. Peichang WANG and Jingrong CAO contributed to Conceptualization, Methodology, Writing–original draft & editing. All authors discussed and edited the manuscript. Competing interests The authors declare no competing interests. Ethical standards The research protocol was approved by the Medical Ethics Committee of Xuanwu Hospital of Capital Medical University (Approval Number: XA[KS2024] 039-002). All methods were carried out in accordance with relevant guidelines and regulations. References Jean, S., Harnod, D. & Hsueh, P. Global threat of carbapenem-resistant gram-negative bacteria. Front. Cell. Infect. Microbiol. 12 , 823684 (2022). Lawandi, A., Yek, C. & Kadri, S. S. Idsa guidance and escmid guidelines: complementary approaches toward a care standard for mdr gram-negative infections. Clin. Microbiol. Infect. 28 (4), 465-469 (2022). Yahav, D. et al. New beta-lactam-beta-lactamase inhibitor combinations. Clin. Microbiol. Rev. 34 (1) (2020). Jin, X. et al. 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Phase i, open-label, safety and pharmacokinetic study to assess bronchopulmonary disposition of intravenous eravacycline in healthy men and women. Antimicrob. Agents. Chemother. 58 (4), 2113-2118 (2014). Tables Table 1. Antimicrobial S usceptibility P rofiles of C arbapenem-resistant O rganisms (CRO) E ravacycline T igecycline O madacycline Ceftazidime- Avibactam AST (S%) ChinaCAST FDA EUCAST FDA CLSL K. pneumoniae 94.3 77.3 19.8 16.9 85.8 bla KPC 94.5 77.0 14.2 17.6 95.6 bla NDM 80.0 60.0 40.0 0 0 bla KPC + bla NDM 100 85.7 14.3 0 28.6 bla KPC + bla IMP 100 100 100 0 0 bla KPC + bla NDM + bla OXA-48 100 100 0.0 50.0 50.0 Metallo-β-lactamase* 92.9 78.6 28.6 7.1 21.4 A. baumannii 99.1 100/0/0 — 100 — MIC₅₀ ( μg /mL ) A. baumannii 0.125 0.5 1 K. pneumoniae 0.5 2 16 bla KPC 0.5 2 16 Metallo-β-lactamase* 0.5 1 16 MIC 90 ( μg /mL ) K. pneumoniae 0.25 1 2 bla KPC 1 4 32 Metallo-β-lactamase* 1 4 32 A. baumannii 1 4 32 MIC Range ( μg /mL ) A. baumannii 0.064–2 0.125–2 0.125–4 K. pneumoniae 0.064–4 0.125–8 0.25–32 bla KPC 0.064–4 0.125–8 0.25–32 Metallo-β-lactamase* 0.125–4 0.25–8 4–32 * Metallo-β-lactamase includes bla NDM and blaIMP ; MIC₅₀: Minimum inhibitory concentration required to inhibit 50% of isolates; MIC₉₀: Minimum inhibitory concentration required to inhibit 90% of isolates. Table 2 . Compare the MIC D istribution of CRO in ERV and TGC baumannii (MIC mg/L) ERV 0.064 0.125 0.25 0.5 1 2 TGC 0.125 3 1 0.25 6 2 0.5 28 24 1 21 28 6 2 1 2 1 2 2 1 pneumoniae (MIC mg/L) ERV 0.064 0.125 0.25 0.5 1 2 4 TGC 0.125 1 0.25 1 1 0.5 4 5 3 1 1 2 13 6 1 2 2 12 16 1 4 16 1 8 1 1 2 Table 3 . Therapeutic R egimens and C linical O utcomes of Tigecycline vs . Eravacycline for CRO I nfections NO. ICU (n) antimicrobial Therapy (n) MIC Range (mg/L) Case Fatality Rate Tigecycline A. baumannii 36 33 TGC+SCF (20) 0.5–2 10% TGC+MEM (5) 1–2 60% TGC+IPM (1) 2 100% TGC+MEM+SCF (3) 1–2 0% TGC+FEP (2) 1–2 0% TGC+MEM+PB (1) 1–2 0% TGC+SCF+CZA (1) 1–2 0% TGC+CIP (1) 2 100% 19.4% RTI 26 25 TGC+SCF (17) 0.5–2 11.7% TGC+MEM (3) 1–2 66.7% TGC+IPM (1) 2 100% TGC+FEP (2) 1–2 100% TGC+MEM+SCF (1) 1 0% TGC+SCF+CZA (1) 1 0% TGC+CIP (1) 2 100% 23.1% BSI 5 4 TGC+SCF (3) 1–2 0% TGC+MEM (1) 1 0% TGC+MEM+SCF (1) 1 0% 0% IAI 4 3 TGC+SCF (2) 1–2 0% TGC+MEM (1) 2 100% TGC+MEM+SCF (1) 1 0% TGC+MEM+PB (1) 1 0% 20% K. pneumoniae 24 22 TGC+SCF (4) 0.5–8 0% TGC+MEM (1) 2 0% TGC+IPM (4) 2–4 0% TGC+IPM (2) 2 0% TGC+CZA (6) 1–8 16.7% TGC+SCF+AK (1) 1 0% TGC+SCF+CZA (1) 1 0% TGC+IPM+CSF (3) 4–8 100% TGC+PB (2) 4 0% 16.7% RTI 12 10 TGC+SCF (3) 0.5–4 0% TGC+MEM (1) 2 0% TGC+IPM (2) 2–4 0% TGC+IPM (1) 2 0% TGC+CZA (3) 2–8 0% TGC+IPM+CZA (1) 4 0% TGC+SCF+IPM (1) 8 100% 8.3% BSI 2 2 TGC+CZA (1) 2 0% TGC+IPM (+CZA (1) 8 100% 50% CNSI 1 1 TGC+PB (1) 4 0% UTI 2 2 TGC+CZA (2) 1–4 50% IAI 7 7 TGC+SCF (1) 1 0% TGC+IPM (2) 2–4 0% TGC+IPM (1) 2 0% TGC+SCF+AMK (1) 1 0% TGC+IPM (+CZA (1) 4 100% TGC+PB (1) 2 0% 14.3 E ravacycline A.baumannii 3 3 ERV+SCF (3) 1 0% RTI 3 3 ERV+SCF (3) 1 0% K. pneumoniae 1 1 ERV+SCF (3) 1 0% RTI 1 1 ERV+SCF (3) 1 0% Abbreviations: TGC, Tigecycline; ERV: Eravacycline; SCF, ceftriaxone sulbactam; MEM, meropenem; IPM, imipenem; BIMP, biapenem; CZA, ceftazidime-avibactam; AMK, amikacin; CIP, ciprofloxacin; PB, polymyxin B; RTI, respiratory tract infection; BSI, bloodstream infection; UTI, urinary tract infection; CNSI, central nervous system infection; IAI, intra-abdominal infection Additional Declarations No competing interests reported. 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11:38:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7052797/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7052797/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86769252,"identity":"1b7398ed-123b-4f93-a7c6-49691e771a7b","added_by":"auto","created_at":"2025-07-15 11:32:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":57807,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparative Distribution of Carbapenem-resistant Pathogens in Clinical Specimens. (a) Distribution of clinical CRKP strains; (b) Distribution of clinical CRAB strains.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7052797/v1/1fd7e844cb5f68ef32bcd76b.png"},{"id":86770651,"identity":"3c56d02a-5fbb-4a77-9d94-ae8b84206005","added_by":"auto","created_at":"2025-07-15 11:40:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":199867,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScreening Process Flowchart for CRO Strains\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7052797/v1/5c29916c06e168af6f74cbd4.png"},{"id":86771316,"identity":"d69562c0-8ac3-4525-896c-fdbb8fb808b0","added_by":"auto","created_at":"2025-07-15 11:48:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":92878,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStatistical Comparison of Antibiotic Breakpoint Criteria across Diverse Drug-resistant Bacterial Pathogens\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7052797/v1/28c4ea76e39eb86ba6bce164.png"},{"id":86769256,"identity":"2dda8845-4969-46e1-b0ac-da2608788129","added_by":"auto","created_at":"2025-07-15 11:32:45","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":91925,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTime-kill Curves of Single Antimicrobial Agents\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea.\u003c/strong\u003e Eravacycline activity against CRKP and CRAB with distinct resistance phenotypes\u003cbr\u003e\n \u003cstrong\u003eb.\u003c/strong\u003e Comparative bactericidal activity of Eravacycline, Tigecycline, and Omadacycline against CRKP\u003cbr\u003e\n \u003cstrong\u003ec.\u003c/strong\u003e Comparative bactericidal activity of Eravacycline, Tigecycline, and Omadacycline against CRAB\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7052797/v1/f020b552f53c8ad2b7d0d379.png"},{"id":96692433,"identity":"8358a355-7ef1-4ce3-a375-9adc887f3dac","added_by":"auto","created_at":"2025-11-25 07:08:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1922457,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7052797/v1/f91106b6-712e-442c-b1e0-e6fc7427b4f9.pdf"},{"id":86769253,"identity":"eb964962-537e-423e-8de9-df2e29838c6f","added_by":"auto","created_at":"2025-07-15 11:32:45","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":20158,"visible":true,"origin":"","legend":"","description":"","filename":"MICDATA.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7052797/v1/d42b05015fbb993eae1b6431.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"First Comparative Evaluation of Omadacycline, Tigecycline, and Eravacycline Against Carbapenem-Resistant Acinetobacter baumannii and Klebsiella pneumoniae in Beijing Tertiary Teaching Hospital: An in Vitro Broth Microdilution Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe global dissemination of carbapenem-resistant Gram-negative organisms (CROs) represents a critical public health threat. Surveillance data from China\u0026rsquo;s CHINET consortium (2024) indicate alarmingly high detection rates: 26.4% for carbapenem-resistant \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e (CRKP) and 66.5% for carbapenem-resistant \u003cem\u003eAcinetobacter baumannii\u003c/em\u003e (CRAB), with even higher prevalence observed in intensive care unit (ICU) patients (CRAB: 78.3%)\u003csup\u003e1,2\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThese pathogens employ diverse resistance mechanisms, primarily mediated by carbapenemase-encoding genes: KPC (Class A serine \u0026beta;-lactamases, dominant in 62% of CRKP isolates); NDM (Class B metallo-\u0026beta;-lactamases, common in \u003cem\u003eE. coli\u003c/em\u003e); and OXA-48 (Class D oxacillinases, prevalent in \u003cem\u003eK. pneumoniae\u003c/em\u003e)\u003csup\u003e3\u003c/sup\u003e. These multidrug-resistant (MDR) phenotypes contribute to high 30-day mortality rates (35% for CRKP and 48% for CRAB infections), attributed to the failure of conventional therapitic options\u003csup\u003e4,5\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eMoreover, transmission of these resistant pathogens within healthcare facilities exacerbates clinical management challenges, as they disseminated through multiple pathways: interpatient contact, contaminated medical devices, and environmental reservoirs. The global proliferation of such high-level resistant organisms underscores \u0026nbsp;the urgent need to develop novel therapeutic strategies and enhanced infection control protocols to mitigate their clinical impact.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCurrent guidelines endorse Eravacycline and Tigecycline as alternative therapeutic options for CRKP and CRAB infections. Tigecycline remains the more widely utilized agent owing to its earlier clinical implementation but exhibits notable limitations: suboptimal serum concentrations, limited alveolar penetration (one-third of serum levels), and elevated coagulation risks associated with high-dose regimens\u003csup\u003e6\u003c/sup\u003e. In contrast, Eravacycline demonstrates superior concentrations in alveolar epithelial lining fluid (8-fold higher than serum levels) and a reduced incidence of coagulation disorders. Nevertheless, its classification as an \u0026quot;alternative agent\u0026quot; persists due to limited Phase III clinical evidence\u0026mdash;particularly for pulmonary and bloodstream infections, where its pharmacodynamic profile indicates substantial therapeutic potential\u003csup\u003e7\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOmadacycline, another next-generation tetracycline, is recommended for treating community-acquired pneumonia owing to its high oral bioavailability. This study constitutes the first tertiary teaching hospital-based comparative analysis of \u003cem\u003ein vitro\u003c/em\u003e susceptibility profiles of ERV, TGC, and OMC against clinical CRKP and CRAB isolates. For CRKP, the current core agent ceftazidime/avibactam was further included in the comparative analysis. These findings provide critical evidence supporting ERV as a potential core antimicrobial agent.\u0026nbsp;\u003c/p\u003e"},{"header":"Materials and methods ","content":"\u003cp\u003e\u003cstrong\u003eClinical isolates\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eA total of 106 non-duplicate CRKP and 117 CRAB isolates were collected from Xuanwu Hospital of Capital Medical University, from January and December 2024. All strains were cryopreserved at -80\u0026deg;C in 15%\u0026ndash;20% glycerol broth prior to recovery. Species identification was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry ( Bruker Daltonics, Germany) following strain revitalization.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGenotyping\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe carbapenemase genotypes of CRKP isolates were determied using immunochromatographic colloidal gold assays (Beijing Jinshanchuan Technology Development Co., Ltd.), with further confirmation via real-time PCR (Ningbo Jinei Biotechnology Co., Ltd.) specifically for isolates exhibiting multi-genotype co-carriage\u003csup\u003e8\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eColloidal gold immunoassay procedure and result interpretation: (1) Sample preparation: Suspend a pure bacterial colony in the supplied extraction buffer, vortex vigorously for 30\u0026ndash;60 seconds, and allow coarse particles to settle.\u0026nbsp;(2) Assay execution: Transfer the clarified supernatant into the sample well of the test device. (3) Result reading: Interpret results within 5\u0026ndash;15 minutes post-assay: Positive,\u0026nbsp;both the test line (T) and control line (C) are clearly visible; Negative,\u0026nbsp;no visible test line (T) is observed, but the control line (C) remains visible; Invalid,\u0026nbsp;no visible control line (C) is detected, regardless of the presence of a T line (repeat the test).\u003c/p\u003e\n\u003cp\u003eThe RT-PCR detection of antibiotic resistance genes encompasses the following critical steps: Firstly, genomic DNA is extracted from bacterial samples. Subsequently, target sequences are amplified using gene-specific primers and a fluorescent probe within a real-time PCR thermal cycler. A positive result is denoted when fluorescence exceeds the threshold value within the predefined cycle limit (Ct \u0026le; 37), whereas the absence of significant increase in fluorescence across the cutoff cycle threshold signifies a negative result. Importantly, the valid \u0026nbsp;interpretation of results requires the successful execution of positive and negative controls, as well as internal extraction controls.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAntimicrobial susceptibility test (AST)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMinimum inhibitory concentrations (MIC) for TGC, ERV, and OMC were determined using the broth microdilution method in accordance with CLSI M07 guidelines\u003csup\u003e[13]\u003c/sup\u003e. Positive controls comprised CRKP strains resistant to all three antibiotics (verified via E-test), whereas \u003cem\u003eE. coli\u003c/em\u003e ATCC25922 served as the negative control. Assays were conducted in 96-well plates: antibiotics were initially dissolved, serially diluted to a stock concentration of 2560 \u0026mu;g/mL, aliquoted, and cryopreserved prior to use. The microbroth doubling dilution method was applied during testing, with final antibiotics concentrations ranging from 32 to 0.064 \u0026mu;g/mL. MIC interpretation followed: Food and Drug Administration (FDA) breakpoints for TGC (\u0026le; 2 \u0026mu;g/mL [susceptible, S], 4 \u0026mu;g/mL [intermediate, I], \u0026ge; 8 \u0026mu;g/mL [resistant, R]) and OMC (\u0026le; 4 \u0026mu;g/mL [S], 8 \u0026mu;g/mL [I], \u0026ge; 16 \u0026mu;g/mL [R])\u003csup\u003e9\u003c/sup\u003e. ChinaCAST breakpoints for ERV (\u0026le; 1 \u0026mu;g/mL [S])\u003csup\u003e10\u003c/sup\u003e. Notably, CLSI and EUCAST breakpoints generally aligned with FDA criteria, with the exception of EUCAST\u0026rsquo;s revised TGC breakpoint (\u0026le; 0.5 \u0026mu;g/mL [S] specifically for \u003cem\u003eK. pneumoniae\u003c/em\u003e)\u003csup\u003e11\u003c/sup\u003e. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTime-kill Assays\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFive strains with known MICs (\u003cem\u003ebla\u003csub\u003eNDM\u003c/sub\u003e\u003c/em\u003e: 0.5 \u0026mu;g/mL, \u003cem\u003ebla\u003csub\u003eNDM\u003c/sub\u003e\u003c/em\u003e+\u003cem\u003ebla\u003csub\u003eKPC\u003c/sub\u003e\u003c/em\u003e: 0.5 \u0026mu;g/mL, \u003cem\u003ebla\u003csub\u003eNDM\u003c/sub\u003e\u003c/em\u003e+\u003cem\u003ebla\u003csub\u003eKPC\u003c/sub\u003e\u003c/em\u003e+\u003cem\u003ebla\u003csub\u003eOXA-48\u003c/sub\u003e\u003c/em\u003e: 0.125 \u0026mu;g/mL, \u003cem\u003ebla\u003csub\u003eKPC\u003c/sub\u003e\u003c/em\u003e: 0.25 \u0026mu;g/mL, and CRAB: 1 \u0026mu;g/mL) were selected. Bactericidal activity was evaluated at their respective MIC concentrations using a 96-well plate. Antimicrobial susceptibility test (AST) was performed via the microbroth dilution method in accordance with CLSI M07-A13. Bacterial growth was monitored by measuring OD600\u003csub\u003e\u0026nbsp;\u003c/sub\u003eabsorbance (0\u0026ndash;24 hours, hourly; 24\u0026ndash;48 hours, every 2 hours; \u0026gt; 48 hours, every 6 hours). Standard curves derived from negative controls were used to calculate log\u003csub\u003e10\u003c/sub\u003e CFU/mL\u003csup\u003e12\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Efficacy Analysis\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDemographic data, combination therapies, and case fatality rates were collected for 223 CRO-infected patients treated with TGC or ERV; OMC was unavailable for this study. Efficacy was evaluated within the predefined MIC ranges. This study adheres to the principles of the Declaration of Helsinki and institutional regulations of Xuanwu Hospital, Capital Medical University. The research protocol was approved by the Medical Ethics Committee of Xuanwu Hospital, Capital Medical University (Clinical Research Approval No.: XA[KS2024]039-002). All patients provided written informed consent upon admission, as detailed in the supplementary materials.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResults were compiled in Microsoft Excel and statistical analyses were performed using SPSS 26.0. Categorical variables were presented as percentages [n (%)] and \u0026nbsp;analyzed using the chi-square (\u0026chi;\u0026sup2;) test. Statistical\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003esignificance was defined as a two-tailed p-value \u0026lt; 0.05.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eClinical Isolates Distribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCRKP and CRAB were most frequently isolated from sputum (57.8% vs. 63.7%) and bronchoalveolar lavage fluid (8.4% vs. 8.5%), followed by blood (9.4% vs. 5.1%), urine (16.0% vs. 8.5%), and drainage fluid (8.4% vs. 5.1%) (Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAntimicrobial Susceptibility Test (AST)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCRKP (n = 106): Susceptibility rates were 94% for ERV, 77% for TGC, and 17% for OMC. MIC\u003csub\u003e50\u003c/sub\u003e/MIC\u003csub\u003e90\u0026nbsp;\u003c/sub\u003evalues were 0.5/1 \u0026mu;g/mL for ERV, 2/4 \u0026mu;g/mL for TGC, and 16/32 \u0026mu;g/mL for OMC.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCRAB (n = 117): All isolates exhibited susceptibility to TGC and OMC, with 99.1% susceptibility to ERV. MIC\u003csub\u003e50\u003c/sub\u003e/MIC\u003csub\u003e90\u003c/sub\u003e values were 0.125/0.25 \u0026mu;g/mL for ERV, 0.5/1 \u0026mu;g/mL for TGC, and 1/2 \u0026mu;g/mL for OMC. OMC demonstrated species-dependent activity, with an 8-fold lower MIC\u003csub\u003e90\u0026nbsp;\u003c/sub\u003eagainst CRAB compared to CRKP (8 vs. 64 \u0026mu;g/mL), outperformed TGC with 4-fold lower MIC\u003csub\u003e90\u0026nbsp;\u003c/sub\u003evalues than ERV against both species (Table 1).\u003c/p\u003e\n\u003cp\u003eStatistical comparisons (\u0026chi;\u0026sup2; test) revealed that ERV exhibited significantly higher susceptibility rates than TGC (EUCAST: \u0026chi;\u0026sup2; = 28.41, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001; FDA: \u0026chi;\u0026sup2; =9.56, \u003cem\u003ep\u003c/em\u003e = 0.002), OMC (FDA: \u0026chi;\u0026sup2; = 34.17, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), and ceftazidime/avibactam (CLSI: \u0026chi;\u0026sup2; = 4.92, \u003cem\u003ep\u003c/em\u003e = 0.027) for CRKP. Subgroup analysis based on carbapenemase type confirmed the superiority of ERV in KPC-producing and metallo-\u0026beta;-lactamase (MBL)-producing CRKP (Figure 2). No significant differences in susceptibility rates were observed for CRAB.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubgroup Analysis by Carbapenemase Type\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKPC-producing CRKP:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eERV exhibited a significantly higher susceptibility rate (94%) than TGC (EUCAST breakpoints \u0026le; 0.5 mg/L: 52.1%, \u0026chi;\u0026sup2; = 31.09, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001; FDA breakpoints \u0026le; 2 mg/L: 77%, \u0026chi;\u0026sup2; = 10.24, \u003cem\u003ep\u003c/em\u003e = 0.001). ERV also showed significantly higher susceptibility than OMC (17%, FDA breakpoints \u0026le; 4 mg/L: \u0026chi;\u0026sup2; = 72.35, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMetallo-\u0026beta;-lactamase (MBL)-producing CRKP:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eERV demonstrated significantly superior activity compared to OMC (FDA breakpoints \u0026le; 4 mg/L: \u0026chi;\u0026sup2; = 19.83, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) and TGC (EUCAST breakpoints \u0026le; 0.5 mg/L: \u0026chi;\u0026sup2; = 8.94, \u003cem\u003ep\u003c/em\u003e = 0.003). Additionally, ERV demonstrated significantly higher activity compared to ceftazidime-avibactam (CLSI breakpoints \u0026le; 8/4 mg/L: \u0026chi;\u0026sup2; = 7.01, \u003cem\u003ep\u003c/em\u003e = 0.008).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTime-kill Assays\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBoth CRAB and CRKP carbapenemase-producing strains showed robust antibacterial activity compared to positive controls, with bacteriostatic effects lasting up to 12 hours. The bacteriostatic efficacy of CRAB was superior to that of CRKP. Among CRKP strains, MBL showed stronger performance than KPC carbapenemase. ERV maintained sustained bactericidal activity (\u0026ge; 3-log\u003csub\u003e10\u003c/sub\u003e reduction) for 24\u0026ndash;36 hours against CRAB and 12\u0026ndash;24 hours against CRKP, outperforming TGC and OMC, which exhibited bacterial regrowth post-12 hours (Figure 4).\u0026nbsp;\u003c/p\u003e\n\u003cp skip=\"true\"\u003e\u003cstrong\u003eClinical Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe analyzed 223 CRO isolates exposed to the targeted antibiotics. A total of 36 CRAB isolates were collected from patients (26 males, 10 females; age range 27\u0026ndash;93 years), with department distribution as follows: Neurology ICU (n = 13), Critical Care ICU (n = 9), Respiratory ICU (n = 5), General Surgery ICU (n = 4), Neurosurgery ICU (n = 2), and Rehabilitation Department (n = 3); ICU patients accounted for 91.7% (33/36) of these cases.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSimilarly, 24 CRKP isolates were obtained from patients (21 males, 3 females; age range 17\u0026ndash;92 years), distributed across departments: General Surgery ICU (n = 6), Critical Care ICU (n = 5), Neurosurgery ICU (n = 4), Neurology ICU (n = 3), Respiratory ICU (n= 2), Emergency ICU (n = 2), Hematology Department (n = 1), and General Medicine Department (n = 1); ICU patients also represented 91.7% (22/24) of the CRKP cases.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong the TGC-treated patients (n= 60; 36 CRAB, 24 CRKP), mortality rates were 19.4% (7/36) for CRAB infections and 16.7% (4/24) for CRKP infections. ERV-treated patients (n= 4; 3 CRAB and 1 CRKP) exhibited a mortality rate of 0% (Table 3).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study presents the first comprehensive \u003cem\u003ein vitro\u003c/em\u003e and clinical evaluation of three tetracycline-class agents against 223 CRO isolates. Key findings are as follows: (a) MIC profiles: ERV demonstrated 4-fold lower MIC values than TGC and 8-fold lower than OMC; (b) Bactericidal superiority: ERV exhibited prolonged bactericidal activity, particularly against CRAB; (c) Clinical correlation: TGC showed suboptimal clinical outcomes, whereas ERV achieved 100% survival in a limited number of cases.\u003c/p\u003e\n\u003cp\u003eCRKP and CRAB were most prevalent in respiratory samples (sputum and bronchoalveolar lavage fluid), highlighting respiratory tract infections as a major clinical burden. Their detection in blood, urine, and cerebrospinal fluid further underscores the need for vigilance in managing bloodstream, urinary, and central nervous system infections.\u003c/p\u003e\n\u003cp\u003eThe escalating prevalence of CRKP and\u0026nbsp;CRAB in clinical isolates has emerged as a critical challenge for contemporary antimicrobial stewardship\u003csup\u003e13,14\u003c/sup\u003e. This study utilized the CLSI-standardized broth microdilution method (M07-A11) to evaluate the \u003cem\u003ein vitro\u003c/em\u003e efficacy of three tetracycline-class agents\u0026mdash;ERV, OMC, and TGC\u0026mdash;against 106 CRKP and 117 CRAB isolates.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor CRKP, ERV (94% susceptibility rate) outperformed TGC (77%) and OMC (17%). Application of EUCAST\u0026apos;s revised TGC breakpoints (\u0026le;0.5 \u0026mu;g/mL) reduced TGC susceptibility to 52.1%, highlighting the impact of breakpoints interpretation variability. For CRAB, all three agents showed comparable activity (ERV: 99.1%, TGC/OMC: 100%), though EUCAST\u0026apos;s lack of Acinetobacter-specific breakpoints complicates global comparisons.\u003c/p\u003e\n\u003cp\u003eEravacycline, a broad-spectrum tetracycline-class antibiotic, exhibits activity against most of MDR bacteria, including CRAB, CRE, Methicillin-Resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (MRSA), and Vancomycin-resistant \u003cem\u003eEnterococci\u003c/em\u003e (VRE). Its enhanced activity is attributed to its reduced efflux pump affinity (50-fold lower than TGC for AcrAB-TolC/MexAB-OprM systems) and lower MICs (8\u0026ndash;32-fold) against TetM/O-mediated resistance\u003csup\u003e15,16\u003c/sup\u003e\u003csup\u003e.\u003c/sup\u003e Superior tissue penetration (8-fold higher alveolar fluid concentration) supports potential utility in pulmonary infections\u003csup\u003e17\u003c/sup\u003e. Notably, this study detected ERV-resistant CRKP and CRAB strains, consistent with international reports\u003csup\u003e18\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDistinct mechanisms underlie Omadacycline resistance in CRKP and CRAB. In CRKP isolates, elevated MICs correlated with overexpression of AcrAB-TolC efflux pump genes\u003csup\u003e19\u003c/sup\u003e, whereas CRAB strains demonstrated lower MICs associated with OprD porin protein deficiency\u003csup\u003e20\u003c/sup\u003e. Omadacycline activity was species-dependent, with an 8-fold lower MIC\u003csub\u003e90\u003c/sub\u003e against CRAB than CRKP\u0026mdash;likely reflecting efflux pump overexpression in CRKP versus porin deficiency in CRAB.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe susceptibility rate of CRKP to Omadacycline was 17%, with approximately 50% resistance observed across strains carrying KPC, NDM, or both carbapenemase genes. Interestingly, two isolates co-harboring KPC, NDM, and OXA-48 genes showed no resistance (one susceptible, one intermediate). This aligns with emerging evidence of Omadacycline activity against OXA-48-producing CRKP. However, our study was limited by small OXA-48 carriers numbers(n = 2) and absence of OXA-48-exclusive isolates, highlighting the need for targeted collection of OXA-48-producing strains to elucidate underlying mechanisms\u003csup\u003e21\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNotably, OMC demonstrates unique pharmacokinetic advantages over other tetracycline-class agents (ERV and TGC). Its oral bioavailability supports utility in mild-to-moderate community-acquired infections\u003csup\u003e22\u003c/sup\u003e. These findings underscore the need for continued surveillance of resistance mechanisms and genotype-phenotype correlations to optimize OMC utilization in antimicrobial stewardship programs.\u003c/p\u003e\n\u003cp\u003eFurther analysis revealed sustained bactericidal activity of ERV throughout the 36-hour observation period, maintaining effective bacterial suppression. In contrast, despite robust initial bactericidal effects, OMC and TGC showed increased bactericidal loads after 12 hours, indicating potential resistance development or time-dependent efficacy reduction.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNotably, ERV exerted concentration-dependent bactericidal effects against both CRAB and CRKP, with higher concentrations correlating to prolonged and enhanced antibacterial activity. At concentrations of 4\u0026ndash;8 \u0026times; MIC, ERV completely suppressed bacterial regrowth over 0\u0026ndash;36 hours\u0026mdash;a effect not observed with TGC or OMC at 2 \u0026times; MIC in time-kill assays.\u003c/p\u003e\n\u003cp\u003eComparative analysis of MIC values revealed that ERV achieved bactericidal activity at significantly lower concentrations than TGC or OMC. Critically, published pharmacokinetic studies demonstrate superior tissue penetration of ERV\u003csup\u003e23\u003c/sup\u003e, particularly in alveolar epithelial lining fluid (ELF) and serum, with concentrations exceeding those of TGC by 2.3-fold and OMC by 3.1-fold, respectively. This pharmacokinetic-pharmacodynamic (PK/PD) profile positions ERV as the most viable candidate for attaining clinically effective bactericidal levels \u003cem\u003ein vivo\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003eThese findings highlight the potential of ERV as a therapeutic option for infections caused by MDR pathogens, particularly in clinical settings where sustained bactericidal activity is crucial for optimizing patient outcomes.\u003c/p\u003e\n\u003cp\u003eLimitations\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eof this study\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003einclude\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eits single-center design, small sample size of ERV-treated cohort, and therapeutic imbalance (predominance of TGC treatment). Further multi-center studies with balanced treatment arms are warranted to validate the clinical efficacy of ERV.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eEravacycline demonstrated broad-spectrum activity and superior bactericidal efficacy against CRKP and CRAB, supported by favorable pharmacokinetics properties. However, its potential as a first-line agent for CRO infections requires further clinical validation. Omadacycline demonstrates species-specific advantages (notably against CRAB) and oral administration utility, while Tigecycline\u0026apos;s limitations\u0026mdash;including suboptimal tissue penetration and elevated adverse event rates\u0026mdash;restrict its role in CRO management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cspan\u003eEthical standards The research protocol was approved by the Medical Ethics Committee of Xuanwu Hospital of Capital Medical University (Approval Number: XA[KS2024] 039-002). All methods were carried out in accordance with relevant guidelines and regulations\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are not publicly available due to the ethical limiting data use to this study. However, a data-sharing protocol will be established in consultation with the hospital for researchers with legitimate requests. The original data files that meet ethical requirements have been uploaded in the supplementary materials section. Raw data supporting the conclusions are available from the corresponding author (JR CAO) upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author (s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by Hebei Provincial Department of Science and Technology (Grant/Award Number: 244X7703D \u0026amp; XA202401102002K), Beijing Municipal Health Commission (Funding number: Discipline Backbone-01-023) and Beijing Natural Science Foundation (Funding number: L256081).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll isolates and demographic data for this study were provided by Xuanwu Hospital of Capital Medical University. We extend our sincere gratitude to all study participants who contributed samples. Additionally, the research team acknowledges the invaluable dedication of participants who generously donated their time and effort to support this investigation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDiandian CHEN, He LAN, and Wenshuo YANG contributed to the study concept and design, data curation, methodology, drafted the manuscript. Dequan TIAN, Yunyi LIU, Rong MIN, Yan WANG, Ying LI, Leyang JU and Qiao SONG contributed to the acquisition of data, data processing, statistical analysis, and reagents. Peichang WANG and Jingrong CAO contributed to Conceptualization, Methodology, Writing\u0026ndash;original draft \u0026amp; editing. All authors discussed and edited the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical standards\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research protocol was approved by the Medical Ethics Committee of Xuanwu Hospital of Capital Medical University (Approval Number: XA[KS2024] 039-002). All methods were carried out in accordance with relevant guidelines and regulations.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJean, S., Harnod, D. \u0026amp; Hsueh, P. Global threat of carbapenem-resistant gram-negative bacteria. \u003cem\u003eFront. Cell. Infect. Microbiol.\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e, 823684 (2022).\u003c/li\u003e\n\u003cli\u003eLawandi, A., Yek, C. \u0026amp; Kadri, S. S. 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Activity of omadacycline alone and in combination against carbapenem-nonsusceptible acinetobacter baumannii with varying minocycline susceptibility. \u003cem\u003eMicrobiol. Spectr.\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e(3), e54222 (2022).\u003c/li\u003e\n\u003cli\u003eTalsma, D. T. et al. Nosocomial transmission of tet(x3), bla (ndm-1) and bla (oxa-97)-carrying acinetobacter baumannii conferring resistance to eravacycline and omadacycline, the netherlands, march to august 2021. \u003cem\u003eEurosurveillance\u003c/em\u003e \u003cstrong\u003e29\u003c/strong\u003e(28) (2024).\u003c/li\u003e\n\u003cli\u003eMorrisette, T. et al. Real-world, multicenter case series of patients treated with oral omadacycline for resistant gram-negative pathogens. \u003cem\u003eInfect. Dis. Ther.\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e(4), 1715-1723 (2022).\u003c/li\u003e\n\u003cli\u003eConnors, K. P. et al. Phase i, open-label, safety and pharmacokinetic study to assess bronchopulmonary disposition of intravenous eravacycline in healthy men and women. \u003cem\u003eAntimicrob. Agents. Chemother.\u003c/em\u003e \u003cstrong\u003e58\u003c/strong\u003e(4), 2113-2118 (2014).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Antimicrobial\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eS\u003c/strong\u003e\u003cstrong\u003eusceptibility\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003cstrong\u003erofiles of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003cstrong\u003earbapenem-resistant\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eO\u003c/strong\u003e\u003cstrong\u003erganisms (CRO)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.9787%;\"\u003e\n \u003ch3\u003e\u0026nbsp;\u003c/h3\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eE\u003c/strong\u003e\u003cstrong\u003eravacycline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT\u003c/strong\u003e\u003cstrong\u003eigecycline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eO\u003c/strong\u003e\u003cstrong\u003emadacycline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCeftazidime-\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAvibactam\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 23.9787%;\"\u003e\n \u003ch3\u003eAST (S%)\u003c/h3\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.1634%;\"\u003e\n \u003ch3\u003eChinaCAST\u003c/h3\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.0782%;\"\u003e\n \u003ch3\u003eFDA\u003c/h3\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.7229%;\"\u003e\n \u003ch3\u003eEUCAST\u003c/h3\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.1634%;\"\u003e\n \u003ch3\u003eFDA\u003c/h3\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.8934%;\"\u003e\n \u003ch3\u003eCLSL\u003c/h3\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eK. pneumoniae\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e94.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.0782%;\"\u003e\n \u003cp\u003e77.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.7229%;\"\u003e\n \u003cp\u003e19.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e16.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e85.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cem\u003ebla\u003csub\u003eKPC\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e94.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.0782%;\"\u003e\n \u003cp\u003e77.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.7229%;\"\u003e\n \u003cp\u003e14.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e17.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e95.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cem\u003ebla\u003csub\u003eNDM\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e80.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.0782%;\"\u003e\n \u003cp\u003e60.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.7229%;\"\u003e\n \u003cp\u003e40.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cem\u003ebla\u003csub\u003eKPC\u003c/sub\u003e\u003c/em\u003e+\u003cem\u003ebla\u003csub\u003eNDM\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.0782%;\"\u003e\n \u003cp\u003e85.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.7229%;\"\u003e\n \u003cp\u003e14.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e28.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cem\u003ebla\u003csub\u003eKPC\u003c/sub\u003e\u003c/em\u003e+\u003cem\u003ebla\u003csub\u003eIMP\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.0782%;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.7229%;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cem\u003ebla\u003csub\u003eKPC\u003c/sub\u003e\u003c/em\u003e+\u003cem\u003ebla\u003csub\u003eNDM\u003c/sub\u003e\u003c/em\u003e+\u003cem\u003ebla\u003csub\u003eOXA-48\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.0782%;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.7229%;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e50.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e50.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003eMetallo-\u0026beta;-lactamase*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e92.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.0782%;\"\u003e\n \u003cp\u003e78.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.7229%;\"\u003e\n \u003cp\u003e28.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e21.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eA. baumannii\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e99.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.0782%;\"\u003e\n \u003cp\u003e100/0/0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.7229%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMIC₅₀ (\u003c/strong\u003e\u003cstrong\u003e\u0026mu;g\u003c/strong\u003e\u003cstrong\u003e/mL\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eA. baumannii\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eK. pneumoniae\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cem\u003ebla\u003csub\u003eKPC\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003eMetallo-\u0026beta;-lactamase*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMIC\u003csub\u003e90\u003c/sub\u003e (\u003c/strong\u003e\u003cstrong\u003e\u0026mu;g\u003c/strong\u003e\u003cstrong\u003e/mL\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eK. pneumoniae\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cem\u003ebla\u003csub\u003eKPC\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003eMetallo-\u0026beta;-lactamase*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eA. baumannii\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMIC Range (\u003c/strong\u003e\u003cstrong\u003e\u0026mu;g\u003c/strong\u003e\u003cstrong\u003e/mL\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eA. baumannii\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0.064\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e0.125\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0.125\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eK. pneumoniae\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0.064\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e0.125\u0026ndash;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0.25\u0026ndash;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003e\u003cem\u003ebla\u003csub\u003eKPC\u003c/sub\u003e\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0.064\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e0.125\u0026ndash;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0.25\u0026ndash;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23.9787%;\"\u003e\n \u003cp\u003eMetallo-\u0026beta;-lactamase*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e0.125\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.8011%;\"\u003e\n \u003cp\u003e0.25\u0026ndash;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.1634%;\"\u003e\n \u003cp\u003e4\u0026ndash;32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.8934%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e* Metallo-\u0026beta;-lactamase includes \u003cem\u003ebla\u003c/em\u003e\u003cem\u003e\u003csub\u003eNDM\u003c/sub\u003e\u003c/em\u003e and \u003cem\u003eblaIMP\u003c/em\u003e; MIC₅₀: Minimum inhibitory concentration required to inhibit 50% of isolates; MIC₉₀: Minimum inhibitory concentration required to inhibit 90% of isolates.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e. Compare the MIC\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003cstrong\u003eistribution of CRO in\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eERV\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;and TGC\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 122px;\"\u003e\n \u003col\u003e\n \u003cli\u003e\u003cem\u003ebaumannii\u003c/em\u003e (MIC mg/L)\u003c/li\u003e\n \u003c/ol\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eERV\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003eTGC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"454\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 122px;\"\u003e\n \u003col start=\"11\"\u003e\n \u003cli\u003e\u003cem\u003epneumoniae\u003c/em\u003e (MIC mg/L)\u003c/li\u003e\n \u003c/ol\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 333px;\"\u003e\n \u003cp\u003eERV\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"7\" valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003eTGC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 83px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 40px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;3\u003c/strong\u003e\u003cstrong\u003e. Therapeutic\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eR\u003c/strong\u003e\u003cstrong\u003eegimens and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003cstrong\u003elinical\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eO\u003c/strong\u003e\u003cstrong\u003eutcomes of Tigecycline vs\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Eravacycline for CRO\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eI\u003c/strong\u003e\u003cstrong\u003enfections\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"548\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003eNO.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003eICU (n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eantimicrobial Therapy\u0026nbsp;(n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003eMIC Range (mg/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eCase Fatality Rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTigecycline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eA. baumannii\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+SCF (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e0.5\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e10%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+MEM (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e60%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+IPM (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+MEM+SCF (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+FEP (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+MEM+PB (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+SCF+CZA (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+CIP (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e19.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRTI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+SCF (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e0.5\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e11.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+MEM (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e66.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+IPM (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+FEP (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+MEM+SCF (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+SCF+CZA (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+CIP (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e23.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBSI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+SCF (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+MEM (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+MEM+SCF (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIAI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+SCF (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+MEM (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+MEM+SCF (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+MEM+PB (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e20%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eK. pneumoniae\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+SCF (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e0.5\u0026ndash;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+MEM (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+IPM (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+IPM (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+CZA (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u0026ndash;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e16.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+SCF+AK (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+SCF+CZA (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+IPM+CSF (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e4\u0026ndash;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+PB (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e16.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRTI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+SCF (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e0.5\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+MEM (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+IPM (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+IPM (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+CZA (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u0026ndash;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+IPM+CZA (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+SCF+IPM (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e8.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBSI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+CZA (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+IPM (+CZA (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e50%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCNSI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+PB (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUTI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+CZA (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e50%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIAI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+SCF (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+IPM (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+IPM (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+SCF+AMK (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+IPM (+CZA (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e100%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTGC+PB (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e14.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eE\u003c/strong\u003e\u003cstrong\u003eravacycline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eA.baumannii\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eERV+SCF\u0026nbsp;(3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRTI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eERV+SCF\u0026nbsp;(3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eK. pneumoniae\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eERV+SCF\u0026nbsp;(3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRTI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 37px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eERV+SCF\u0026nbsp;(3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 109px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: TGC, Tigecycline; ERV: Eravacycline; SCF, ceftriaxone sulbactam; MEM, meropenem; IPM, imipenem; BIMP, biapenem; CZA, ceftazidime-avibactam; AMK, amikacin; CIP, ciprofloxacin; PB, polymyxin B; RTI, respiratory tract infection; BSI, bloodstream infection; UTI, urinary tract infection; CNSI, central nervous system infection; IAI, intra-abdominal infection\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","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":"Carbapenem-Resistant Acinetobacter baumannii, Carbapenem-Resistant Klebsiella pneumoniae, Broth microdilution method, Time-kill assays, tetracycline-class antibiotics","lastPublishedDoi":"10.21203/rs.3.rs-7052797/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7052797/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe rising prevalence of\u003cstrong\u003e \u003c/strong\u003ecarbapenem-resistant organisms (CROs) necessitates the exploration of novel therapeutics options. This study evaluated the \u003cem\u003ein vitro\u003c/em\u003e\u003cstrong\u003e activity \u003c/strong\u003eand clinical outcomes of three tetracycline-class antibiotics—Eravacycline (ERV), Tigecycline (TGC), and Omadacycline (OMC)—against regional CRO isolates. A total of 233 non-duplicate clinical CRO isolates (106 carbapenem-resistant \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e [CRKP] and 117 carbapenem-resistant \u003cem\u003eAcinetobacter baumannii\u003c/em\u003e [CRAB]) were collected from Xuanwu Hospital in 2024. Antimicrobial susceptibility was determined via broth microdilution to measure minimum inhibitory concentrations (MIC), complemented by 0–48 hour time-kill assays. Clinical outcomes of patients treated with TGC or ERV were analyzed. Key findings included:\u003c/p\u003e\n\u003cp\u003e1. \u003cstrong\u003eAntimicrobial Potency\u003c/strong\u003e: ERV demonstrated superior\u0026nbsp;\u003cem\u003ein vitro\u003c/em\u003e\u0026nbsp;activity, with MIC\u003csub\u003e90\u003c/sub\u003e values of 0.5 mg/L (ERV), 2 mg/L (TGC), and 4 mg/L (OMC)—4-fold lower than TGC and 8-fold lower than OMC.\u003c/p\u003e\n\u003cp\u003e2. \u003cstrong\u003eTime-kill Assays\u003c/strong\u003e:\u003cstrong\u003e \u003c/strong\u003eERV achieved sustained bactericidal activity at 4–8 × MIC (a novel observation), particularly against\u0026nbsp;CRAB, maintaining \u0026gt;3-log₁₀ CFU/mL reduction for 24–36 hours—2.3-fold longer than TGC and 3.1-fold longer than OMC. While effective against CRKP, ERV demonstrated pathogen-specific advantages for CRAB.\u003c/p\u003e\n\u003cp\u003e3. \u003cstrong\u003eClinical Correlation\u003c/strong\u003e: The ERV-treated cohort (n = 4) exhibited 0% mortality, compared to TGC-treated patients with 18.9% mortality for CRAB (7/37) and 16.7% for CRKP (4/24).\u003c/p\u003e\n\u003cp\u003eERV displayed enhanced bactericidal activity and lower resistance thresholds compared to TGC. Preliminary clinical data support its potential as a core therapeutic agent for CRO infections, warranting futher validation in multicenter studies.\u003c/p\u003e","manuscriptTitle":"First Comparative Evaluation of Omadacycline, Tigecycline, and Eravacycline Against Carbapenem-Resistant Acinetobacter baumannii and Klebsiella pneumoniae in Beijing Tertiary Teaching Hospital: An in Vitro Broth Microdilution Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-15 11:32:41","doi":"10.21203/rs.3.rs-7052797/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":"145cdd73-0ddf-446b-931b-2504080737b3","owner":[],"postedDate":"July 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":51489006,"name":"Health sciences/Diseases"},{"id":51489007,"name":"Health sciences/Medical research"},{"id":51489008,"name":"Biological sciences/Microbiology"}],"tags":[],"updatedAt":"2025-11-25T07:08:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-15 11:32:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7052797","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7052797","identity":"rs-7052797","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}