1. Proteus mirabilis – analysis of a concealed source of carbapenemases and development of a diagnostic algorithm for detection.
- Author
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Hamprecht, Axel, Sattler, Janko, Noster, Janina, Stelzer, Yvonne, Fuchs, Frieder, Dorth, Vivien, Gatermann, Sören G., and Göttig, Stephan
- Subjects
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CARBAPENEMASE , *NUCLEOTIDE sequencing , *KLEBSIELLA pneumoniae , *AGAR , *MEROPENEM , *ERTAPENEM , *MUPIROCIN - Abstract
To analyse carbapenemases in Proteus mirabilis and assess the performance of carbapenemase detection assays. Eighty-one clinical P. mirabilis isolates with high-level resistance at least to ampicillin (>32 mg/L) or previous detection of carbapenemases were selected and investigated by three susceptibility testing methods (microdilution, automated susceptibility testing, and disk diffusion), six phenotypic carbapenemase assays (CARBA NP, modified carbapenemase inactivation method [CIM], modified zinc-supplemented CIM, simplified CIM, faropenem, and carbapenem-containing agar), two immunochromatographic assays, and whole-genome sequencing. Carbapenemases were detected in 43 of 81 isolates (OXA-48-like [ n = 13]; OXA-23 [ n = 12]; OXA-58 [ n = 12]; New Delhi metallo-β-lactamase (NDM) [ n = 2]; Verona integron–encoded metallo-β-lactamase (VIM) [ n = 2]; Imipenemase (IMP) [ n = 1]; Klebsiella pneumoniae carbapenemase (KPC) [ n = 1]). Carbapenemase-producing Proteus were frequently susceptible to ertapenem (26/43; 60%), meropenem (28/43; 65%), ceftazidime (33/43; 77%), and some even to piperacillin-tazobactam (9/43; 21%). Sensitivity/specificity of phenotypic tests were 30% (CI: 17–46%)/89% (CI: 75–97%) for CARBA NP, 74% (CI: 60–85%)/82% (CI: 67–91%) for faropenem, 91% (CI: 78–97%)/82% (CI: 66–92%) for simplified CIM, and 93% (CI: 81–99%)/100% (CI: 91–100%) for modified zinc-supplemented CIM. An algorithm for improved detection was developed, which demonstrated sensitivity/specificity of 100% (CI: 92–100%)/100% (CI: 91–100%) on the 81 isolates, and 100% (CI: 29–100%)/100% (CI: 96–100%) in a prospective analysis of additional 91 isolates. Interestingly, several OXA-23-producing isolates belonged to the same clonal lineage reported previously from France. Current susceptibility testing methods and phenotypic tests frequently fail to detect carbapenemases in P. mirabilis , which could result in inadequate antibiotic treatment. In addition, the non-inclusion of bla OXA-23/OXA-58 in many molecular carbapenemase assays further impedes their detection. Therefore, the prevalence of carbapenemases in P. mirabilis is likely underestimated. With the herein proposed algorithm, carbapenemase-producing Proteus can be easily identified. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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