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Polymyxin Acute Kidney Injury: Dosing and Other Strategies to Reduce Toxicity
Roger L Nation1, Maria Helena P Rigatto2,3, Diego R Falci4,5
1Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Australia. roger.nation@monash.edu.
Abstract:
Polymyxins are valuable antimicrobials for the management of multidrug-resistant Gram-negative bacteria; however, nephrotoxicity associated with these drugs is a very common side effect that occurs during treatment. This article briefly reviews nephrotoxic mechanisms and risk factors for polymyxin-associated acute kidney injury (AKI) and discusses dosing strategies that may mitigate kidney damage without compromising antimicrobial activity. Polymyxins have a very narrow therapeutic window and patients requiring treatment with these drugs are frequently severely ill and have multiple comorbidities, which increases the risk of AKI. Notably, there is a significant overlap between therapeutic and toxic plasma polymyxin concentrations that substantially complicates dose selection. Recent dosing protocols for both colistin and polymyxin B have been developed and may help fine tune dose adjustment of these antibiotics. Minimizing exposure to modifiable risk factors, such as other nephrotoxic agents, is strongly recommended. The dose should be carefully selected, particularly in high-risk patients. The administration of oxidative stress-reducing drugs is a promising strategy to ameliorate polymyxin-associated AKI, but still requires support from clinical studies.
Insights
Polymyxins effectively treat resistant bacteria but can cause kidney damage (AKI). New dosing strategies and avoiding other nephrotoxic drugs may reduce this risk in vulnerable patients.
Area of Science:
- Pharmacology
- Nephrology
- Infectious Diseases
Background:
- Polymyxins are crucial for treating multidrug-resistant Gram-negative infections.
- Nephrotoxicity is a significant and common adverse effect of polymyxin therapy.
- Patients often have comorbidities, increasing susceptibility to acute kidney injury (AKI).
Purpose of the Study:
- To review nephrotoxic mechanisms and risk factors for polymyxin-associated AKI.
- To discuss dosing strategies for mitigating kidney damage while maintaining efficacy.
- To highlight potential interventions for reducing polymyxin-induced nephrotoxicity.
Main Methods:
- Review of existing literature on polymyxin nephrotoxicity.
- Analysis of risk factors contributing to polymyxin-associated AKI.
- Discussion of current and emerging dosing protocols for colistin and polymyxin B.
Main Results:
- Polymyxins have a narrow therapeutic window, complicating dose selection.
- Significant overlap exists between therapeutic and toxic plasma concentrations.
- Several modifiable risk factors, including co-administration of nephrotoxic agents, contribute to AKI.
Conclusions:
- Careful dose selection is critical, especially in high-risk patients.
- Minimizing exposure to nephrotoxic agents is strongly recommended.
- Oxidative stress-reducing agents show promise but require clinical validation for preventing polymyxin-associated AKI.
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