Intravenous combined with aerosolised polymyxin versus intravenous polymyxin alone in the treatment of pneumonia caused by multidrug-resistant pathogens: a systematic review and meta-analysis

Colistin has been used to treat nosocomial pneumonia (NP) caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) via different administration routes. Whether patients may benefit from aerosolised colistin as adjunctive treatment was contradictory. We aimed to clarify the safety and efficacy of administering aerosolised and intravenous (IV-AS) colistin versus intravenous (IV) colistin alone in patients with NP caused by MDR-GNB. Two reviewers independently evaluated and extracted data from PubMed, EMBASE and Cochrane databases. Primary outcomes were clinical response rate, all-cause mortality (ICU or hospital), microbiological eradication and nephrotoxicity. Pooled odds ratios (ORs) were calculated and significance was determined by the Z test. Nine eligible studies involving 672 participants were included. The overall clinical response rate (improvement and cure) was significantly higher in the IV-AS group than that in the IV group [OR = 1.81, 95% confidence interval (CI) 1.30-2.53; P = 0.0005]. Patients treated with IV-AS colistin showed a higher rate of pathogen eradication (OR = 1.66, 95% CI 1.11-2.49; P = 0.01) and lower all-cause mortality compared with IV colistin (OR = 0.69, 95% CI 0.50-0.95; P = 0.02). Nephrotoxicity did not differ significantly between IV-AS and IV groups (five studies; 383 patients) (OR = 1.11, 95% CI 0.69-1.80; P = 0.67). These data indicate that IV-AS colistin has additional benefits compared with IV colistin alone. Clinicians should be encouraged to give combined administration routes in critically ill patients with NP caused by MDR-GNB.