Intravenous combined with aerosolised polymyxins vs intravenous polymyxins monotherapy for ventilator-associated pneumonia: A systematic review and meta-analysis

Polymyxins were applied via different administration routes to treat ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Gram-negative bacteria (CR-GNB). The potential benefits of aerosolised polymyxins as adjunctive treatment for patients are contradictory. This review assessed the safety and efficacy of intravenous (IV) combined with aerosolised polymyxins vs IV polymyxins monotherapy in patients with VAP caused by CR-GNB. Two reviewers independently evaluated and extracted data from PubMed, Embase, Cochrane library and Web of Science. The primary outcome was all-cause mortality and secondary outcomes included clinical cure rate, clinical improvement rate, microbiological eradication rate and nephrotoxicity. Differences for dichotomous outcomes were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Eleven eligible studies were included. The results showed that compared with IV polymyxins monotherapy, IV plus aerosolised polymyxins therapy significantly reduced all-cause mortality rate (OR = 0.75, 95% CI 0.57–0.99, P = 0.045) and improved clinical improvement rate (OR = 1.62, 95% CI 1.02–2.60, P = 0.043) and microbial eradication rate (OR = 2.07, 95% CI 1.40–3.05, P = 0.000). However, there were no significant differences in terms of clinical cure rate (OR = 1.59, 95% CI 0.96–2.63, P = 0.072) and nephrotoxicity (OR = 1.14, 95% CI 0.80–1.63, P = 0.467) for IV plus aerosolised polymyxins therapy. Subgroup analysis revealed that the clinical improvement rate was significantly improved in case-control studies. Aerosolised polymyxins may be a useful adjunct to IV polymyxins for patients with CR-GNB VAP.