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. 2021 Jan 21;8(2):ofab026.
doi: 10.1093/ofid/ofab026. eCollection 2021 Feb.

Colistin Nephrotoxicity: Meta-Analysis of Randomized Controlled Trials

Khalid Eljaaly  1   2 , Monique R Bidell  3 , Ronak G Gandhi  3 , Samah Alshehri  1   2 , Mushira A Enani  4 , Ahmed Al-Jedai  5   6 , Todd C Lee  7
Affiliations

Colistin Nephrotoxicity: Meta-Analysis of Randomized Controlled Trials

Khalid Eljaaly et al. Open Forum Infect Dis. .

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.

Keywords: colistimethate; colistin; kidney; nephrotoxicity; polymyxin.

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Figures

Figure 1.
Figure 1.
Flow diagram of the study selection process.
Figure 2.
Figure 2.
Forest plot showing the risk ratios of nephrotoxicity using random-effects models in patients receiving colistin versus comparators. Vertical line, “no difference” point between the 2 groups; horizontal line, 95% confidence interval; squares, risk ratios; diamonds, pooled risk ratios. CI, confidence interval; MH, Mantel-Haenszel.
See this image and copyright information in PMC

References

    1. Tsuji BT, Pogue JM, Zavascki AP, et al. International consensus guidelines for the optimal use of the polymyxins: endorsed by the American College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), International Society for Anti-infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious Diseases Pharmacists (SIDP). Pharmacotherapy 2019; 39:10–39. - PMC - PubMed
    1. Polymyxin B Product Information. Bedford, OH: Bedford Laboratories; 2012.
    1. Chien HT, Lin YC, Sheu CC, et al. Is colistin-associated acute kidney injury clinically important in adults? A systematic review and meta-analysis. Int J Antimicrob Agents 2020; 55:105889. - PubMed
    1. Eljaaly K Dose and duration of intraventricular antibiotic therapy in meningitis. Clin Microbiol Infect 2016; 22:817. - PubMed
    1. Betrosian AP, Frantzeskaki F, Xanthaki A, Douzinas EE. Efficacy and safety of high-dose ampicillin/sulbactam vs. colistin as monotherapy for the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia. J Infect 2008; 56:432–6. - PubMed