Polymyxins

The polymyxin class of antibiotics includes polymyxin B and polymyxin E (colistin), the latter of which is administered clinically as colistin methane sulfate intravenously. Although an older class of antibiotics, their use has been revitalized by the multi-drug and panresistant strains of P. aeruginosa, A. baumannii, and carbapenemresistant Enterobacteriaceae that has arisen over the last decade. Notably, these agents were shelved in the early 1970’s because of high rates of nephrotoxicity and neurotoxicity relative to other available antibiotic agents. Their pharmacokinetic/pharmacodynamic properties have only recently begun to be elucidated, and antimicrobial effect is correlated with fAUC/MIC exposures. To date, these experiments have largely been undertaken in vitro or in animal infection models. As previously mentioned, 1-log reductions in colony forming unit require fAUC/MIC ratios of approximately 12.2 to 22.8 in both thigh- and lung-infection murine models. Unfortunately, the protein binding of colistin in humans, particularly critically ill patients, has not been established; therefore, for dosing strategies, a total AUC/MIC ratio of approximately 60 has been used to target drug concentrations

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Last date updated on April, 2024