Last-Resort Antibiotics Show No Survival Edge in Hospital Pneumonia Study

Carbapenems, the powerful antibiotics that many doctors reach for when hospital pneumonia strikes, may not deliver the survival advantage that clinicians in resource-limited settings often assume. A new retrospective cohort study from a tertiary care hospital in Karachi, Pakistan, has found that patients treated with carbapenem-based regimens for hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) fared no better than those given alternative antibiotics, a finding with significant implications for antimicrobial stewardship in low- and middle-income countries where these last-line drugs are heavily relied upon.

The research, published in the Journal of Pharmacy & Pharmaceutical Sciences, followed 93 adult patients over a single year, including 62 cases of HAP and 31 cases of VAP. Hospital-acquired pneumonia refers to lung infections that develop 48 hours or more after admission, while ventilator-associated pneumonia arises at least 48 hours after endotracheal intubation. Both conditions rank among the most common and deadliest healthcare-associated infections in developing countries, driving prolonged hospitalization, escalating costs, and the spread of antimicrobial resistance.

The burden in such settings is striking. A meta-analysis cited by the researchers reported VAP rates of 18.5 per 1,000 ventilator-days in low- and middle-income countries, more than double the figures seen in high-income settings. Yet in Pakistan, most existing studies have focused exclusively on intensive care units, leaving the toll of pneumonia in general wards largely unrecognized. The new study addressed that gap by screening all 24,565 patients admitted during the study period and identifying eligible cases through ICD-10 codes, with diagnoses confirmed independently by a board-certified infectious disease pharmacist and an infectious disease physician using American Thoracic Society and Infectious Diseases Society of America definitions.

Carbapenem-based therapy, delivered almost entirely as meropenem at a standard dose of 1 gram every eight hours with renal adjustments, was used in 65.6 percent of cases. The most frequently prescribed non-carbapenem agents were piperacillin-tazobactam, ceftazidime, and colistin. Patients were assigned to treatment groups based on their initial empirical regimen within 48 hours of diagnosis, following an intention-to-treat principle, and were required to have received at least 48 hours of the assigned therapy.

The headline result was a statistical null. Among HAP patients, mortality was 31.6 percent with carbapenem therapy versus 29.2 percent without it, an unadjusted risk ratio of 1.08 with a 95 percent confidence interval spanning 0.50 to 2.36. For VAP, mortality was 65.2 percent versus 50.0 percent respectively, a risk ratio of 1.30 with a confidence interval of 0.61 to 2.77. Neither difference approached statistical significance, and hospital stay durations were similarly indistinguishable between the groups. Subgroup analyses by critical illness status, ICU admission, and diabetes also revealed no significant mortality benefit from carbapenems.

What did matter was the pneumonia type itself. VAP carried a crude mortality of 61.3 percent, dramatically higher than the 30.6 percent seen in HAP, a difference that was statistically significant. This aligns with published estimates attributing roughly 48 percent mortality to VAP, particularly among critically ill and surgical ICU patients. The finding underscores the importance of timely diagnosis and rigorous infection prevention measures around mechanical ventilation, rather than simply escalating antibiotic potency.

The microbiology told an equally sobering story. Gram-negative bacteria dominated both pneumonia types, led by Acinetobacter baumannii and Pseudomonas aeruginosa, organisms notorious for surviving on hospital surfaces and accumulating multidrug resistance. Polymicrobial infections were significantly more common in VAP, affecting 41.9 percent of those patients compared with just 8.1 percent of HAP cases, while culture-negative pneumonia was frequent in HAP at 45.2 percent but uncommon in VAP. Most strikingly, crude mortality appeared highest among patients in the Acinetobacter group at 70.4 percent overall, reaching 77.8 percent even among carbapenem-treated patients, followed by the Pseudomonas group at 31.3 percent. These differences between treatment groups were not statistically significant, but the pattern suggests that the pathogen, not the drug class, may be the decisive factor in survival.

An exploratory biomarker analysis of the 38 deceased patients added a physiological dimension to the findings. White blood cell counts rose significantly from diagnosis to death in both HAP and VAP patients, and neutrophil percentages climbed significantly in VAP cases, reflecting progressive infection and systemic inflammation as patients deteriorated. Other markers, including C-reactive protein, procalcitonin, temperature, and creatinine, showed no significant changes, likely due to small sample sizes and wide individual variability.

The authors are careful to frame these results as hypothesis-generating rather than definitive, and the caveats are substantial. The study was retrospective and single-center, with a small sample that produced wide confidence intervals incapable of excluding a clinically meaningful benefit or harm of carbapenems; a meaningful mortality reduction in HAP and VAP would typically fall in the range of 5 to 10 percent absolute risk reduction. Confounding by indication looms large, since carbapenem-treated patients were sicker at baseline, with higher proportions of critical illness, VAP, and diabetes. A planned multivariable logistic regression to adjust for confounders proved unfeasible because severity scores such as SOFA and APACHE II and key biomarker data were missing from the retrospective dataset, leaving all analyses unadjusted.

Despite these limitations, the study offers rare real-world evidence from a high-burden, resource-limited setting, and its message resonates with a growing international literature. A systematic review and meta-analysis by Howatt and colleagues found no significant advantage of carbapenems over other beta-lactams in VAP, and recent work suggests that carbapenems and newer beta-lactam/beta-lactamase inhibitor combinations such as ceftazidime-avibactam and ceftolozane-tazobactam produce comparable outcomes. Together, these findings point toward a future of personalized, pathogen-directed therapy guided by local resistance patterns and individual risk factors, rather than reflexive escalation to broad-spectrum carbapenems. For hospitals in Pakistan and similar settings, the results argue for strengthening antibiotic stewardship programs, investing in early pathogen detection, and pursuing adequately powered prospective studies that can finally settle whether these expensive, resistance-driving drugs truly earn their place at the bedside.

Subject of Research: Comparative clinical outcomes of carbapenem-based versus non-carbapenem antibiotic therapy for hospital-acquired and ventilator-associated pneumonia in a resource-limited setting

Article Title: Carbapenem-based versus non-carbapenem therapy for hospital-acquired and ventilator-associated pneumonia in a resource-limited setting: a retrospective cohort study of clinical outcomes

Article References: Kanwal, U., Muhammad, I. N., Zehra, A., Shah, S. S. A. M., Abro, F., Ansari, T., Rahim, N., Munawar, R., & Hussain, M. (2026). Carbapenem-based versus non-carbapenem therapy for hospital-acquired and ventilator-associated pneumonia in a resource-limited setting: a retrospective cohort study of clinical outcomes. Journal of Pharmacy & Pharmaceutical Sciences, 29, Article 17336. https://doi.org/10.3389/jpps.2026.17336

Image Credits: AI Generated

DOI: 10.3389/jpps.2026.17336

Keywords: hospital-acquired pneumonia, ventilator-associated pneumonia, carbapenems, meropenem, antimicrobial resistance, antimicrobial stewardship, Acinetobacter baumannii, Pseudomonas aeruginosa, Pakistan, retrospective cohort study, low- and middle-income countries, mortality