Ahmad, Sharjeel

Abstract Rationale: Current guidelines recommend a short course of antibiotic therapy for ventilator-associated pneumonia (VAP) caused by non-fermenting gram-negative bacilli (NF-GNB). However, this approach has been associated with an increased risk of pneumonia recurrence. This meta-analysis aims to address inconsistencies in the literature and evaluate the efficacy of short-course versus long-course antibiotic therapy for VAP, particularly in cases due to NF- GNB. Methods: We systematically searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing short versus long courses of antibiotic therapy in patients with VAP. The primary outcomes were the risk of all-cause mortality and pneumonia recurrence. Data were analyzed using RevMan 5.4, with risk ratio (RR) and mean difference (MD) as effect measures. Results: Our pooled analysis included seven RCTs. There was no significant difference in all- cause mortality between short- and long-course antibiotic regimens (RR 1.02; 95% CI: 0.88-1.18; Figure 1). However, a short course of antibiotics increased the incidence ofpneumonia recurrence, particularly in patients with VAP due to NF-GNB (RR 1.64; 95% CI: 1.18-2.29; Figure 1). There were no significant differences between the two regimens regarding the duration of mechanical ventilation (MD 0.01 days; 95% CI: -0.51 to 0.53 days), ICU (MD 0.10 days; 95% CI: -1.00 to 1.20 days) and hospital stay (MD -0.63 days; 95% CI: -3.18 to 1.91 days), or subsequent infection with or acquisition of resistant organisms (RR 0.89; 95% CI: 0.63-1.24). Conclusions: Our meta-analysis suggests that while a short course of antibiotics increases the risk of pneumonia recurrence in NF-GNB VAP, it does not impact mortality compared to a longer course. The clinical significance of the increased recurrence of pneumonia remains uncertain, as it did not result in worse clinical outcomes. A practical approach incorporating validated clinical criteria and biomarker thresholds to guide the duration of antibiotic therapy may be more effective for patients with NF-GNB VAP. Larger RCTs are needed to drawdefinitive conclusions in this population.