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Antibiotics (Basel). 2019 Mar 14;8(1). pii: E24. doi: 10.3390/antibiotics8010024.

Polymyxin Acute Kidney Injury: Dosing and Other Strategies to Reduce Toxicity.

Author information

1
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Australia. roger.nation@monash.edu.
2
Infectious Diseases Service, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90035-903, Brazil. mhprigatto@gmail.com.
3
Infectious Diseases Service, Hospital de Clinicas de Porto Alegre, Porto Alegre 90035-903, Brazil. mhprigatto@gmail.com.
4
Infectious Diseases Service, Hospital de Clinicas de Porto Alegre, Porto Alegre 90035-903, Brazil. diego.falci@gmail.com.
5
Health and Human Development Post-Graduation Program, Universidade La Salle, Canoas 92010-000, Brazil. diego.falci@gmail.com.
6
Infectious Diseases Service, Hospital de Clinicas de Porto Alegre, Porto Alegre 90035-903, Brazil. azavascki@hcpa.edu.br.
7
Department of Internal Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-903, Brazil. azavascki@hcpa.edu.br.

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.

KEYWORDS:

acute kidney injury; colistin; dosing; pharmacokinetics/pharmacodynamics; polymyxin B

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