Abstract
ABSTRACTPolymyxin antibiotics are disfavored owing to their potential clinical toxicity, especially nephrotoxicity. However, the dry antibiotic development pipeline, together with the increasing global prevalence of infections caused by multidrug-resistant (MDR) gram-negative bacteria, have renewed clinical interest in these polypeptide antibiotics. This review highlights the current information regarding the mechanisms of resistance to polymyxins and their molecular epidemiology. Knowledge of the resistance mechanisms and epidemiology of these pathogens is critical for the development of novel antibacterial agents and rapid treatment choices.
Highlights
Polymyxins have been used for over 50 years in both veterinary and human medicine
The results showed that mgrB alterations were the most frequent source of polymyxin resistance in Brazilian clinical settings[17]
A few months after being reported for the first time, mcr-1 has been detected in bacterial isolates from animals, humans, and the environment in various countries in South America, North America, Europe, Asia, and Africa, and has been identified in several bacterial genera, including Escherichia, Shigella, Klebsiella, Salmonella, Enterobacter, and E. coli[31,32,33,34,35]
Summary
Polymyxins have been used for over 50 years in both veterinary and human medicine. Colistin is a decapeptide administered either as colistin sulfate, an oral prodrug, or as colistin methanesulfonate (CMS) when used intravenously[1]. Extensive use of colistin as a livestock food additive, along with its inappropriate use in clinical medicine, has led to reservoirs of high levels of resistance in gram-negative bacteria, such as Acinetobacter baumannii, Enterobacteriaceae (Klebsiella pneumoniae and Escherichia coli), and Pseudomonas aeruginosa[7]. Some chromosomal mutations have been associated with colistin resistance, as they lead to changes in the outer membrane elements essential to polymyxin function.
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