Prevention of colistin induced nephrotoxicity: a review of preclinical and clinical data

Abstract

The emergence of antimicrobial resistance in Gram-negative bacteria is a concerning challenge for health systems. The polymyxins, including colistin, are one of the limited available options these pathogens management. Nephrotoxicity, beside neurotoxicity is the major dose-limiting adverse reaction of polymyxins, with an up to 60% prevalence. As oxidative stress, inflammatory pathways and apoptosis are considered as main mechanisms of colistin-induced kidney damage, various studies have evaluated antioxidant and/or antiapoptotic compounds for its prevention. In this article, we reviewed animal and human studies on these probable preventive measures. PubMed, Scopus, and google scholar databases were searched using several combination of “colistin”, “polymyxin E”, “CMS”, “Colistimethate sodium”, “nephrotoxicity”, “kidney injury”, “kidney damage”, “renal injury”, “renal damage”, “nephroprotectants”, “renoprotective”, “nephroprotective”, and “prevention”. All eligible articles including animal and human studies up to the end of 2020 were included. Most of available studies are in vivo researches on anti-oxidant and anti-apoptotic agents like NAC, vitamin C and E, silymarin, and curcumin which mostly showed promising findings. However, limited human studies on NAC and vitamin C did not demonstrate considerable efficacy. So, before proposing these compounds, further well-designed randomized clinical trials are necessary.