In‐Vitro Activity of Ceftazidime‐Avibactam and Comparator Agents Against Carbapenem‐Resistant Gram‐Negative Isolates at a Tertiary Care Hospital in Lahore, Pakistan: A Cross‐Sectional Study

ABSTRACT

Carbapenem‐resistant Gram‐negative bacteria are WHO critical priority pathogens with few treatment options. Ceftazidime‐avibactam (CAZ–AVI) inhibits serine carbapenemases (KPC, OXA‐48‐like) but not metallo‐β‐lactamases, which are common in South Asia. Local data are scarce; we assessed CAZ–AVI and comparator activity in Pakistan. In this laboratory‐based cross‐sectional study, consecutive non‐duplicate carbapenem‐resistant isolates from a tertiary care centre in Lahore (December 2024–May 2025) were tested by MIC and disc diffusion with CLSI interpretation. The primary outcome was CAZ–AVI susceptibility with exact binomial 95% confidence intervals; comparisons used Fisher's exact test, McNemar's test, and multivariable logistic regression. Of 210 isolates, 200 had CAZ–AVI results; susceptibility was 70.5% (141/200; 95% CI 63.7–76.7). It varied by sample source ( p  = 0.008), from 81.2% in blood cultures to 38.5% (5/13) in other specimens, but not by organism, department, age, or gender. In paired comparisons, CAZ–AVI susceptibility exceeded gentamicin, ciprofloxacin, piperacillin‐tazobactam, and trimethoprim‐sulfamethoxazole, was similar to amikacin, and was lower than colistin, fosfomycin, and tigecycline. Among 59 resistant isolates, colistin (94.5%), fosfomycin (92.9%), tigecycline (79.5%), and chloramphenicol (76.7%) were most active. Sample source was the only independent predictor (other specimens vs blood culture: adjusted OR 0.18, 95% CI 0.05–0.68; imprecise). CAZ–AVI was active in vitro against 70.5% of carbapenem‐resistant Gram‐negative isolates. Because nearly one‐third were resistant, these findings support surveillance and susceptibility‐guided rather than empirical use. Metallo‐β‐lactamase production is a plausible but unconfirmed explanation. Molecular characterization and evaluation of CAZ–AVI plus aztreonam are needed.