Efficacy of Ceftazidime-avibactam against Multidrug-resistant Gram-negative Pathogens in ICU Patients: A Crosssectional Study from a Subhimalayan Tertiary Care Hospital

Introduction: Antimicrobial Resistance (AMR) is a pressing global health issue, posing challenges in clinical management, increasing morbidity and mortality rates, and burdening healthcare systems economically. The present study assesses the in-vitro efficacy of Ceftazidime-Avibactam (CZA) against Multidrug-Resistant (MDR) Gram-negative isolates from Intensive Care Unit (ICU) patients, comparing it to other betalactam/beta-lactamase inhibitors, with a focus on CarbapenemResistant Enterobacterales (CRE), Extended-Spectrum BetaLactamase (ESBL)- producing Enterobacterales, and MDR Pseudomonas aeruginosa. Aim: To determine the sensitivity pattern of CZA against various MDR Gram-negative isolates from ICU patient samples and compare its efficacy with other second-line drugs. Materials and Methods: The present cross-sectional observational study was conducted over a six-month period from January to June 2021 on 94 MDR bacterial isolates obtained from Intensive Care ICU patients at the Himalayan Institute of Medical Sciences (HIMS), Swami Rama Himalayan University (SRHU) Dehradun, Uttrakhand, India. All clinical samples received from ICU patients with clinically suspected sepsis were included in the study. These samples were routinely processed in the bacteriology laboratory following Standard Operating Procedures (SOPs). Bacterial identification and Antimicrobial Susceptibility Testing (AST) were performed using the VITEK-2 automated system from bacterial colonies isolated after overnight incubation. Demographic characteristics of the patients were systematically recorded and analysed. E-test strips for CZA were only applied to those bacterial isolates identified as MDR Enterobacteriaceae and Pseudomonas spp. Statistical analyses were conducted to determine antimicrobial susceptibility rates, with statistical significance set at p<0.05. Results: Among the 94 MDR Gram-negative isolates, Klebsiella pneumoniae and Escherichia coli were the most prevalent pathogens, comprising 34 (36.2%) and 32 (34.0%) of samples, respectively. CZA demonstrated a sensitivity rate of 35 (37.2%) across 94 samples, with limited efficacy against 46 CRE isolates i.e., 10(21.7%) and 15 MDR Pseudomonas aeruginosa i.e., 4 (26.6%), and no efficacy against Acinetobacter baumannii 0 (0%). Notably, CZA outperformed amoxicillin-clavulanic acid and piperacillin-tazobactam in-vitro activity against ESBLproducing Enterobacteriaceae but showed reduced efficacy against 61 carbapenem resistant isolates when compared to last-resort antibiotics like colistin 39 (63.9%). Conclusion: The findings indicate CZA’s moderate efficacy against ESBL-producing Gram-negative bacteria but limited effectiveness against CRE and MDR P. aeruginosa in ICU settings. These results suggest a need for careful evaluation of CZA use in ICU settings and highlight the importance of ongoing antimicrobial surveillance and the potential for combination therapy to address rising MDR infections.