The safety of polymyxin antibiotics

Abstract

Introduction: The emergence of multidrug-resistant gram-negative bacteria has led to the increasing use of polymyxins. Nephrotoxicity and, to a lesser degree, neurotoxicity occur often during systemic polymyxin therapy. Scientific evidence regarding safety associated with polymyxins remains limited.

Areas covered: Case reports/case series, observational studies and clinical trials assessing safety and toxicity of polymyxins were critically reviewed.

Expert opinion: Polymyxins are drugs with a narrow therapeutic range. Nephrotoxicity is associated with both host factors and polymyxin exposure, and recent studies suggest that the relative risk of nephrotoxicity is similar for colistin and polymyxin B. Studies that have examined the safety of polymyxins have several limitations. Considering the available evidence, toxicities that may develop while on polymyxin therapy most often are mild to moderate in magnitude and reversible in nature. Strategies to minimize toxicity associated with polymyxins have evolved and include avoidance of toxic medications, careful dosing, use of critical care, therapeutic drug monitoring and development of polymyxin derivatives. However, given that polymyxin use has re-emerged in an era of increased antimicrobial resistance, the presence of other treatment modalities may be limited. Therefore, clinicians must consider overall risk to benefit ratio of continuing versus stopping polymyxin treatment and optimize minimization strategies to reduce polymyxin-induced toxicities.

Keywords:

• antimicrobial resistance
• colistin
• nephrotoxicity
• neurotoxicity
• polymyxin B
• polymyxins
• safety
• toxicity

Declaration of interest

M Falagas participated in advisory boards of Achaogen, AstraZeneca, Infectopharm, Tetraphase, and Pfizer; received lecture honoraria from Cipla, Merck, Sanofi and Novartis; and received research support from Angelini, Astellas, and Rokitan. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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