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The safety of polymyxin antibiotics
Theodoros Kelesidis1, Matthew E Falagas2,3
1a 1 University of California, David Geffen School of Medicine, Division of Infectious Diseases, Department of Medicine , Los Angeles, CA 90095, USA.
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.
Insights
Polymyxin antibiotics, crucial for multidrug-resistant infections, can cause kidney and nerve toxicity. While often mild and reversible, careful monitoring and risk-benefit assessment are vital for safe use.
Area of Science:
- Pharmacology
- Infectious Diseases
- Nephrology
Background:
- The rise of multidrug-resistant gram-negative bacteria necessitates increased use of polymyxins.
- Polymyxin therapy is associated with significant nephrotoxicity and neurotoxicity.
- Limited scientific evidence exists regarding the safety profile of polymyxins.
Purpose of the Study:
- To critically review the scientific evidence on the safety and toxicity of polymyxins.
- To summarize current understanding of polymyxin-induced adverse events.
- To discuss strategies for minimizing polymyxin toxicity.
Main Methods:
- A critical review of case reports, case series, observational studies, and clinical trials.
- Assessment of studies evaluating the safety and toxicity of polymyxins.
- Synthesis of available data on polymyxin adverse effects.
Main Results:
- Polymyxins possess a narrow therapeutic range.
- Nephrotoxicity is linked to host factors and polymyxin exposure; colistin and polymyxin B show similar nephrotoxicity risks.
- Observed toxicities are typically mild to moderate and reversible, though study limitations exist.
Conclusions:
- Strategies to mitigate polymyxin toxicity include avoiding concurrent nephrotoxic drugs, precise dosing, critical care, therapeutic drug monitoring, and developing new polymyxin derivatives.
- Given limited alternatives in the era of antimicrobial resistance, clinicians must weigh the risks and benefits of polymyxin treatment.
- Optimizing toxicity minimization strategies is crucial for safe and effective polymyxin use.
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