What is the most effective antibiotic monotherapy for severe Pseudomonas aeruginosa infection? A systematic review and meta-analysis of randomized controlled trials.

Objectives: To compile the evidence of sub-groups of patients with Pseudomonas aeruginosa (P. aeruginosa) infection from randomized control trials (RCTs) evaluating different definite antipseudomonal monotherapies for severe P.aeruginosa infection.

Methods: Systematic review and meta-analysis of RCTs that assessed monotherapy with an antipseudomonal drug versus another antipseudomonal for definite treatment, and reported on the subgroup of patients with P. aeruginosa infection. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, LILACS and the reference lists of included trials. The primary outcome was 30-day mortality. Results were pooled using fixed-effect and random-effects model as appropriate. Relative risk (RR) and 95% confidence intervals (CI) were calculated.

Results: A total of 76 RCTs and 1,681 patients with pseudomonal infection were included. Due to the low number of studies which reported our outcomes of interest, all subgroups analyses were underpowered. No difference in all-cause mortality was found for any direct antibiotic comparison. Higher clinical failure rates of carbapenems vs piperacillin-tazobactam were observed for pneumonia in 2 RCTs (RR 2.55, 95% CI 1.29-5.03, I²=0%, n=2), and higher microbiological failure rates with carbapenems versus other comparators (RR 1.24, 95% CI 1.02-1.51, I²=0%, n=23). Patients treated with imipenem were more likely to develop resistance to the study drug versus comparators (RR 2.33, 95% CI 1.61-3.38, I² =0%, n=7).

Conclusions: In this systematic review and meta-analysis of definite antipseudomonal monotherapy for P. aeruginosa infection, we found no evidence for clinical benefit differences among direct antibiotic comparisons, but all subgroup analyses were underpowered to detect significant differences.