Therapeutic Specification of the Last Resort Polymyxins: An Intelligent Approach

Abstract

Polymyxins, especially polymyxin B and colistin (polymyxin E), are the last resort antibiotics among a few reserve antibiotics still showing potentiality against Gram-negative superbugs. Globally, during the alarming situation of fast-spreading antibiotic resis-tanceinGram-negativebacteria,thetherapeuticapplicationof polymyxinsshouldberationalandtarget-specificconsideringtheir pharmacokinetic(PK)andpharmacodynamic(PD)characteristics. IntravenouspolymyxinBshowsrelativelyhigherplasmaprotein binding and excessive renal tubular reabsorption; it invariably exists in the plasma for longer periods, maintaining the minimum inhibitoryconcentration(MIC)properly, andmostlyareexcretedoutthroughanonrenalpathway. Ontheotherhand, intravenous inactive colistimethate sodium is bio-converted in the blood and kidneys into the active colistin moiety that manifests relatively higher colistin concentration in the urinary tract for longer duration possessing the MIC statically. This study comprehensively evaluated the PK and PD data of polymyxins assuming that the therapeutic specification of polymyxin B in bloodstream infections and colistin in urinary tract infections caused by multidrug-resistant Gram-negative bacteria may be an intelligent approach during the emergence of antibiotic resistance. The therapeutic specification of polymyxins may effectively reduce the progression of polymyxin resistance and optimize its therapeutic outcomes in the treatment of life-threatening infections.