Colistin Nephrotoxicity: Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Nephrotoxicity is a known adverse effect of polymyxin antibiotics, including colistin. Although previous meta-analyses have aimed to characterize colistin-associated nephrotoxicity risk relative to other antibiotics, included studies were observational in nature with high risk of confounding and heterogeneity. We conducted this systematic review and meta-analysis of exclusively randomized controlled trials (RCTs) to evaluate the incidence of nephrotoxicity associated with colistin versus minimally nephrotoxic antibiotics. Methods: We searched PubMed, EMBASE, Cochrane Library, and 3 trial registries for RCTs comparing the nephrotoxicity of colistin to nonpolymyxin antibiotics. Randomized controlled trials that used aminoglycosides were excluded. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. The study outcome was the rate of nephrotoxicity. Results: Five RCTs with a total of 377 patients were included. Most patients received colistin for pneumonia in the intensive care unit, and the comparators were β-lactam-based regimens. Colistimethate sodium was dosed at 9 million units/day (300 mg/day of colistin base activity), with administration of a loading dose in 4 studies. The nephrotoxicity incidence in patients who received colistin was 36.2% (95% CI, 23.3% to 51.3%). The nephrotoxicity rate was significantly higher in the colistin arm than comparators (RR, 2.40; 95% CI, 1.47 to 3.91; P ≤. 001; I2 = 0%), and the number needed to harm was 5. Findings persisted upon one-study-removed-analysis. Conclusions: This meta-analysis of RCTs found a colistin-associated nephrotoxicity rate of 36.2% and an increase in this risk compared with β-lactam-based regimens by 140%. Colistin should be regarded as a last-line agent and safer alternatives should be considered when possible.