Clinical use of intravenous polymyxin B for the treatment of patients with multidrug-resistant Gram-negative bacterial infections: An evaluation of the current evidence

Matthew E Falagas; Margarita Kyriakidou; Georgios L Voulgaris; Filippos Vokos; Sevasti Politi; Konstantinos S Kechagias

doi:10.1016/j.jgar.2020.12.026

Clinical use of intravenous polymyxin B for the treatment of patients with multidrug-resistant Gram-negative bacterial infections: An evaluation of the current evidence

J Glob Antimicrob Resist. 2021 Mar:24:342-359. doi: 10.1016/j.jgar.2020.12.026. Epub 2021 Jan 21.

Authors

Matthew E Falagas¹, Margarita Kyriakidou², Georgios L Voulgaris³, Filippos Vokos⁴, Sevasti Politi⁴, Konstantinos S Kechagias⁵

Affiliations

¹ Alfa Institute of Biomedical Sciences, Athens, Greece; Department of Medicine, Henry Dunant Hospital Center, Athens, Greece; Department of Medicine, Tufts University School of Medicine, Boston, MA, USA. Electronic address: m.falagas@aibs.gr.
² Alfa Institute of Biomedical Sciences, Athens, Greece; School of Applied Mathematical and Physical Sciences, National Technical University, Athens, Greece.
³ Alfa Institute of Biomedical Sciences, Athens, Greece; Laboratory of Pharmacokinetics and Toxicology, Department of Pharmacy, 401 General Military Hospital, Athens, Greece.
⁴ School of Applied Mathematical and Physical Sciences, National Technical University, Athens, Greece.
⁵ Alfa Institute of Biomedical Sciences, Athens, Greece.

PMID: 33486122
DOI: 10.1016/j.jgar.2020.12.026

Abstract

Objectives: The epidemic dimensions of the emergence of multidrug-resistant (MDR) Gram-negative bacterial infections have led to the revival of old antibiotics, including the polymyxins.

Methods: We performed a review and meta-analysis to evaluate the current literature data regarding the effectiveness and safety of intravenous polymyxin B in patients with MDR Gram-negative bacterial infections and the overall mortality and nephrotoxicity in patients treated with intravenous polymyxin B either as monotherapy or combination therapy.

Results: A total of 5 prospective and 28 retrospective studies, 1 cross-sectional study, 2 retrospective case series and 7 case reports provided data regarding the effectiveness and/or toxicity of intravenous polymyxin B. All-cause mortality of 2910 patients (from 27 studies) who received intravenous polymyxin B was 41.2% (95% CI 35.5-47.0%). All-cause nephrotoxicity of 2994 patients (from 28 studies) treated with intravenous polymyxin B was 40.7% (95% CI 35.0-46.6%). Renal failure among 2111 patients (from 14 studies) was 11.2% (95% CI 8.7-13.9%).

Conclusion: Mortality of patients treated with intravenous polymyxin B is similar to the literature-reported mortality of patients treated with intravenous colistin, while nephrotoxicity associated with polymyxin B use is possibly milder compared with colistin use based on literature data. Head-to-head prospective studies would help to clarify the benefit of polymyxin B over colistin. However, a critical evaluation of the existing worldwide literature data supports the need for availability of the intravenous formulation of polymyxin B as a potentially useful option for the treatment of patients with MDR and extensively drug-resistant (XDR) Gram-negative bacterial infections.

Keywords: Acinetobacter baumannii; Extensively drug-resistant; Klebsiella pneumoniae; Nephrotoxicity; Polymyxins; Pseudomonas aeruginosa.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review

MeSH terms

Cross-Sectional Studies
Drug Resistance, Multiple, Bacterial
Gram-Negative Bacterial Infections* / drug therapy
Humans
Polymyxin B* / adverse effects
Prospective Studies
Retrospective Studies

Substances

Polymyxin B