Carbapenems versus β-lactam and β-lactamase inhibitors for treatment of nosocomial pneumonia: A systematic review and meta-analysis

BACKGROUND: Carbapenems and β-lactam and β‐lactamase inhibitors (BLBLIs) have been used empirically in nosocomial pneumonia, but their efficacy and safety are controversial. OBJECTIVE: We carried out a systematic review with meta-analysis to evaluate the efficacy and safety of carbapenems versus BLBLIs against nosocomial pneumonia. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, CNKI, Wangfang, VIP and Sinomed were searched systematically through April 29, 2023 for clinical trials comparing carbapenems with BLBLIs for treatment of nosocomial pneumonia. Random-effects models were used to evaluate the impact of treatment on the risk ratio (RR) of all-cause mortality, clinical response, microbiologic response, resistance by Pseudomonas aeruginosa, adverse effects (AEs), and serious adverse effects. The quality of the evidence was assessed with the Cochrane risk of bias tool. The review was registerted in the INPLASY (INPLASY202340113). RESULTS: Seven randomized controlled trials containing 3306 patients met our inclusion criteria Our meta-analysis showed no significant difference in all-cause mortality (RR = 0.88, 95% confidence interval [CI] = 0.75–1.03, I(2) = 0%) or clinical cure (1.02, 0.96–1.09, 30%) or clinical failure (1.19, 0.97–1.47, 0%) or microbiologic clinical cure (0.98, 0.89–1.06, 40%) or Pseudomonas aeruginosa resistance (RR 2.43, CI 0.86–6.81, 49%, P = 0.09) or adverse events (0.98, 0.93–1.02, 0%) between carbapenems groups versus BLBLIs groups, but a significant difference was found for severe adverse events (RR 0.83, CI 0.73−0.94, 0%). CONCLUSION: Differences in the prevalence of mortality, clinical cure, or clinical failure were not observed between carbapenems groups versus BLBLIs groups in terms of nosocomial pneumonia. The use of carbapenems was linked to a tendency towards the emergence of P. aeruginosa resistance, however, no statistically significant difference was observed.