A six-month survey of laboratory samples at a tertiary care hospital in Lahore, Pakistan, has found that the antibiotic combination ceftazidime-avibactam inhibited 70.5% of carbapenem-resistant Gram-negative bacteria collected from routine clinical specimens. The cross-sectional study, which analyzed 200 isolates with a ceftazidime-avibactam test result out of 210 carbapenem-resistant isolates recovered between December 2024 and May 2025, also mapped how the drug compared with a panel of older and newer alternatives. The results, published in MicrobiologyOpen, show substantial but incomplete activity in a setting where resistance is common, and they arrive with an important caveat: the measurements describe what happened in the laboratory, not how patients fared on treatment.
Ceftazidime-avibactam pairs a third-generation cephalosporin with avibactam, a non-β-lactam β-lactamase inhibitor. The design targets a specific vulnerability in resistant bacteria: enzymes that dismantle β-lactam antibiotics. Avibactam restores ceftazidime’s activity by blocking class A β-lactamases, including the Klebsiella pneumoniae carbapenemase (KPC), class C enzymes such as AmpC, and selected class D enzymes, notably OXA-48. What it cannot do is inhibit metallo-β-lactamases such as New Delhi metallo-β-lactamase (NDM), which are widespread in South Asia. That mechanistic gap makes local susceptibility data particularly valuable, because the fraction of isolates the drug can defeat depends heavily on which carbapenemase enzymes circulate in a given hospital.
The Lahore team classified an isolate as carbapenem-resistant if it was non-susceptible to meropenem or imipenem under Clinical Laboratory Standards Institute standards, and they retained only the first non-duplicate isolate per patient-organism combination. Species identification and susceptibility testing were performed with the Vitek 2 automated system, with ceftazidime-avibactam assessed by minimum inhibitory concentration testing and disc diffusion. The cohort skewed toward older and hospitalized patients: 77.6% of isolates came from patients over 40, and the specimens originated mainly from intensive care and critical care units (36.7%) and inpatient wards (30.0%). Blood cultures supplied the largest share of samples at 39.0%, and Escherichia coli was the most frequent organism at 48.6%, followed by Pseudomonas species at 22.4% and Klebsiella species at 18.1%.
The headline number of 70.5% susceptibility (141 of 200 isolates, with a 95% confidence interval of 63.7 to 76.7) means that roughly three in ten carbapenem-resistant isolates were resistant to the drug. In the broader susceptibility panel, only colistin (94.8% of 194 tested), fosfomycin (87.1% of 155), tigecycline (86.6% of 157), and chloramphenicol (82.4% of 159) showed higher in-vitro susceptibility than ceftazidime-avibactam, though the authors stress that the number of isolates tested differed between agents, complicating direct comparison. Nitrofurantoin was susceptible in 10 of 11 tested isolates, a figure the small denominator renders unreliable. All other β-lactams and β-lactam/β-lactamase inhibitor combinations performed substantially worse.
Subgroup analyses revealed a largely uniform picture across organism groups and hospital locations. Susceptibility ranged from 65.7% in Klebsiella species to 73.7% in E. coli, a difference that was not statistically significant (p = 0.80). Across departments, rates spanned from 60.6% in the high-dependency unit to 76.1% in intensive care, again without significant variation (p = 0.34). The one variable that did matter was sample source (p = 0.008): blood-culture isolates showed the highest susceptibility at 81.2% (65 of 80), while a small and clinically heterogeneous group of other specimen types, just 13 isolates, showed the lowest at 38.5%, an estimate the authors flag as imprecise given its wide confidence interval of 13.9 to 68.4. Respiratory and pus/wound isolates fell in between at 66.7% and 66.0% respectively. Age and gender showed no significant association.
When the researchers restricted attention to the 59 ceftazidime-avibactam-resistant isolates, the search for alternatives became urgent. Colistin retained the most activity (94.5% of 55 tested), followed by fosfomycin (92.9% of 42), tigecycline (79.5% of 44), and chloramphenicol (76.7% of 43). Conventional Gram-negative agents fared poorly: amikacin held 42.4% susceptibility, gentamicin 32.2%, and tobramycin just 20.0% of 20 tested. The fluoroquinolones were largely inert, with ciprofloxacin and levofloxacin each susceptible in only 11.9% of 59 isolates. Piperacillin-tazobactam managed 10.2%, cefepime 7.4%, and amoxicillin-clavulanate 2.3%. No resistant isolate was susceptible to ampicillin, cefixime, ceftriaxone, cefuroxime, meropenem, or imipenem, the last two being expected since carbapenem resistance defined the cohort.
Paired comparisons on isolates tested against both ceftazidime-avibactam and a comparator, analyzed with McNemar’s test, sharpened the picture. The drug significantly outperformed gentamicin (70.5% versus 55.5%), ciprofloxacin (70.4% versus 31.7%), piperacillin-tazobactam (70.4% versus 50.3%), and trimethoprim-sulfamethoxazole (69.6% versus 33.1%), each with p < 0.001. It matched amikacin (70.5% versus 70.0%, p = 1.00). Conversely, colistin (94.6% versus 70.1%), tigecycline (86.4% versus 70.1%), and fosfomycin (87.7% versus 71.2%) all showed significantly higher susceptibility. The authors emphasize that these paired analyses describe differences in in-vitro susceptibility only and do not indicate differences in clinical effectiveness.
A multivariable logistic regression model confirmed that sample source was the only variable independently associated with ceftazidime-avibactam susceptibility. Isolates from the small heterogeneous other-source category had significantly lower odds of susceptibility than blood-culture isolates (adjusted odds ratio 0.18, 95% confidence interval 0.05 to 0.68, p = 0.013), though the authors caution that this estimate rests on just 13 tested isolates and carries considerable imprecision. Respiratory samples (adjusted odds ratio 0.52) and pus/wound/tissue/body fluid samples (adjusted odds ratio 0.52) showed numerically lower odds that did not reach statistical significance. Organism group, department, and gender were not independently associated with susceptibility.
The authors offer a plausible but unproven explanation for the resistance they observed: the local distribution of carbapenemase enzymes. Ceftazidime-avibactam is generally active against KPC and OXA-48-like β-lactamases but not against metallo-β-lactamases including NDM, VIM, and IMP types. In regions with high NDM prevalence, reduced susceptibility is expected depending on the local burden of MBL-producing strains. Because the study did not perform molecular characterization of carbapenemase genes, this remains a hypothesis consistent with regional epidemiology rather than an established cause. Other mechanisms, including KPC variants with altered avibactam interactions, porin loss, efflux pump overexpression, and AmpC hyperproduction, particularly relevant for Pseudomonas species, may also contribute. The higher susceptibility in bloodstream isolates, the authors speculate, might reflect earlier detection and less established biofilm formation compared with respiratory and wound isolates, where long hospital stays, mechanical ventilation, and indwelling devices favor biofilm development and resistant phenotypes.
The study’s limitations frame how far its conclusions travel. It was conducted at a single center over six months, which may limit generalizability to hospitals with different antibiotic use practices. Carbapenemase genes were not characterized, so the mechanisms underlying resistance remain undetermined. The analysis was performed at the isolate level on specimens collected for routine diagnostic purposes, and the laboratory dataset did not record whether an isolate represented infection or colonization, antibiotic exposure before specimen collection, or patient outcomes. Susceptibility proportions therefore cannot be extrapolated directly to the proportion of treatable infections in the hospital population. Several subgroups were small, and the number of isolates tested varied considerably between antibiotics because not every agent was tested against every isolate in routine practice, with full-cohort denominators ranging from 11 to 210. Sensitivity analyses handling duplicate laboratory accession numbers confirmed the robustness of the primary estimate, yielding 71.7% and 72.4% under alternative duplicate-handling assumptions, both within the primary confidence interval. The authors conclude that with nearly one-third of isolates resistant, the findings do not support empirical ceftazidime-avibactam monotherapy in the absence of susceptibility data, but rather support ongoing local surveillance and targeted, susceptibility-guided use of the drug, particularly in severe infections, alongside routine molecular characterization of carbapenemase genes to clarify resistance mechanisms and inform local treatment guidance.
Subject of Research: In-vitro susceptibility of ceftazidime-avibactam and comparator antibiotics against carbapenem-resistant Gram-negative clinical isolates at a Pakistani tertiary care hospital
Article Title: 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
Article References: Yunus, F., Rehman, O. U., Murtaza, M., Mazhar, S., Samadi, A., & Raza, A. A. (2026). 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. MicrobiologyOpen, 15(6), Article e70449. https://doi.org/10.1002/mbo3.70449
Image Credits: AI Generated
DOI: 10.1002/mbo3.70449
Keywords: ceftazidime-avibactam, carbapenem-resistant Gram-negative bacteria, antimicrobial resistance, Pakistan, susceptibility testing, Klebsiella pneumoniae carbapenemase, NDM, colistin, tigecycline, fosfomycin, antimicrobial stewardship, cross-sectional study
News Source: Drew Townsend. (November 5, 2026). Ceftazidime-Avibactam Inhibited 70.5% of Carbapenem-Resistant Gram-Negative Isolates in Lahore Hospital Study. Scienmag.
