Colistin

Abstract

Infections caused by multi-drug resistant (MDR) Gram-negative bacteria have increased worldwide due to rampant use of broad-spectrum antibiotics. Besides MDR, at present, extensively drug-resistant (XDR), and pan-drug-resistant (PDR) strains of various Gram-negative organisms harboring various resistance mechanisms are encountered, posing significant challenges to microbiologists and clinicians. Paucity of development of new antibiotics have led researchers to revive older antibiotics, one of them being the polymyxins as a last resort to combat MDR-GNBs. Polymyxin B and polymyxin E(colistin) are available as approved medical formulations. Polymyxins act against Gram-negative bacteria such as Acinetobacter species, Pseudomonas aeruginosa, Klebsiella species, and Enterobacter species. Colistin (polymyxin E) was recognized in 1950 and is available in two forms for human use i.e. colistin sulfate (CS) and colistin methanesulfonate (CMS). Lipid A component of the lipopolysaccharide (LPS), is the primary target of colistin. It is administered by i.v., route, as an aerosolized formulation, and by the intraventricular route. EUCAST and CLSI have advised broth microdilution method (BMD) as the standard reference method for Minimum inhibitory concentration (MIC). Minimum plasma concentrations (Cmin) of colistin higher than 2.5mg/L have been associated with an increased nephrotoxicity. Colistin resistance is due to the mobilized colistin resistance (mcr) gene which confers plasmid-mediated resistance to the drug. Colistin and its derivatives are the last resort agents in the treatment of MDR-GNBs. But with increasing resistance it has become difficult to treat dreadful infections caused due to these superbugs. Research is needed to improve upon colistin formulations. © 2022 Elsevier Inc. All rights reserved