Development and Application of a Pragmatic Algorithm to Guide Definitive Carbapenemase Testing to Identify Carbapenemase-Producing <i>Pseudomonas aeruginosa</i>

A minimum inhibitory concentration (MIC) derived algorithm, predictive of carbapenemase production, was developed using a challenge set (<i>n</i> = 92) of <i>Pseudomonas aeruginosa</i> (PA), including carbapenemase-producing (CP), cephalosporinase and/or efflux/porin mutation...

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Bibliographic Details
Main Authors: Christian M. Gill, Tomefa E. Asempa, David P. Nicolau
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/9/11/738
Description
Summary:A minimum inhibitory concentration (MIC) derived algorithm, predictive of carbapenemase production, was developed using a challenge set (<i>n</i> = 92) of <i>Pseudomonas aeruginosa</i> (PA), including carbapenemase-producing (CP), cephalosporinase and/or efflux/porin mutation, and wild-type isolates. Broth microdilution MICs to clinically relevant anti-pseudomonal agents were utilized. The algorithm was applied to 1209 clinical PA isolates from a US surveillance program. Confirmatory genotypic (Xpert<sup>®</sup> Carba-R assay) and phenotypic (mCIM/eCIM) testing for carbapenemases was conducted on algorithm-derived isolates. With the algorithm, carbapenem resistance alone resulted in poor specificity to identify CP-PA (54%) within the challenge set of isolates. Inclusion of cefepime, ceftazidime, and piperacillin/tazobactam non-susceptibility resulted in a specificity of 66%. Ceftolozane/tazobactam resistance further improved specificity (89%). Of the 1209 isolates, 116 met criteria (carbapenem-resistant and non-susceptibility to cefepime, ceftazidime, and piperacillin/tazobactam) for confirmatory testing. Carba-R and mCIM/eCIM identified five (all <i>bla</i><sub>VIM</sub>-positive) and seven carbapenemase-producing isolates, respectively. This MIC algorithm combined with genotypic/phenotypic carbapenemase testing is a pragmatic and streamlined approach to identify CP-PA.
ISSN:2079-6382