Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing Position Statements on Polymyxin B and Colistin Clinical Breakpoints. (13th February 2020)

• Record Type: Journal Article
• Authors: Satlin, Michael J; Lewis, James S; Weinstein, Melvin P; Patel, Jean; Humphries, Romney M; Kahlmeter, Gunnar; Giske, Christian G; Turnidge, John
• Is Part Of: Clinical infectious diseases. Volume 71:Number 9(2020)
• Page Start: e523
• Page End: e529
• Publication Date: 2020-02-13
• Subjects: colistin -- polymyxin -- CLSI -- EUCAST -- clinical breakpoints; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa121
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Recent data on polymyxin pharmacokinetics, pharmacodynamics, toxicity, and clinical outcomes suggest these agents have limited clinical utility. Pharmacokinetics-pharmacodynamics data show a steady-state concentration of 2 μg/mL is required for killing bacteria with colistin minimum inhibitory concentrations of 2 μg/mL. Less than 50% of patients with normal renal function achieve this exposure, and it is associated with high risk of nephrotoxicity. This exposure does not achieve bacterial stasis in pneumonia models. Randomized and observational studies consistently demonstrate increased mortality for polymyxins compared with alternative agents. The Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) are 2 global organizations that establish interpretive criteria for in vitro susceptibility data. CLSI has recently taken the step to eliminate the "susceptible" interpretive category for the polymyxins, whereas EUCAST maintains this interpretive category. This viewpoint describes the opinions of these organizations and the data that were used to inform their perspectives. Abstract : Recent pharmacokinetic, pharmacodynamic, microbiological and clinical data demonstrate the polymyxins have limited clinical utility, although they frequently demonstrate in vitro activity against extensively drug resistant Gram negative bacteria. CLSI and EUCAST interpretation of polymyxin MICs are described.