Pitfalls in genotypic antimicrobial susceptibility testing caused by low expression of blaKPC in Escherichia coli
There is a growing interest in the rapid genotypic identification of antimicrobial resistance (AMR). In routine diagnostics, we detected multiple KPC-positive Escherichia coli (KPC-Ec) with discordant phenotypic meropenem susceptibility from a single patient’s blood cultures, which prompted a more t...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
29 July 2021
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| In: |
The journal of antimicrobial chemotherapy
Year: 2021, Volume: 76, Issue: 11, Pages: 2795-2801 |
| ISSN: | 1460-2091 |
| DOI: | 10.1093/jac/dkab267 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/jac/dkab267
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| Author Notes: | Kaan Kocer, Sabrina Klein, Dagmar Hildebrand, Johannes Krall, Klaus Heeg, Sébastien Boutin, Dennis Nurjadi |
| Summary: | There is a growing interest in the rapid genotypic identification of antimicrobial resistance (AMR). In routine diagnostics, we detected multiple KPC-positive Escherichia coli (KPC-Ec) with discordant phenotypic meropenem susceptibility from a single patient’s blood cultures, which prompted a more thorough investigation.We investigated the potential clinical relevance of, and the mechanism behind, discordant phenotypic and genotypic meropenem susceptibility in KPC-Ec.WGS was used to perform a comparative analysis of the isolates’ genetic characteristics and their blaKPC-2 locus. Expression of blaKPC-2 was determined by quantitative PCR and the potency of meropenem hydrolysis was determined using a semi-quantitative carbapenem inactivation method. An in vivo infection assay using Galleria mellonella was performed to assess the potential clinical relevance of KPC expression in E. coli.Despite the presence of blaKPC-2, three of five isolates were susceptible to meropenem (MICVITEK2≤0.25 mg/L), while two isolates were resistant (MICVITEK2≥16 mg/L). The isolates with high MICs had significantly higher blaKPC-2 expression, which corresponds to phenotypic meropenem inactivation. The genetic environment of blaKPC-2, which may impact KPC production, was identical in all isolates. In vivo infection assay with G. mellonella suggested that meropenem was effective in reducing mortality following infection with low-expressing KPC-Ec.Our findings clearly highlight a limitation of genotypic AMR prediction for blaKPC. For the time being, genotypic AMR prediction requires additional analysis for accurate antibiotic therapy decision-making. |
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| Item Description: | Gesehen am 28.01.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1460-2091 |
| DOI: | 10.1093/jac/dkab267 |