Pitfalls in genotypic antimicrobial susceptibility testing caused by low expression of blaKPC in Escherichia coli

• Verfasst von: Kocer, Kaan [VerfasserIn]
• Verfasst von: Klein, Sabrina [VerfasserIn]
• Verfasst von: Hildebrand, Dagmar [VerfasserIn]
• Verfasst von: Krall, Lars Johannes [VerfasserIn]
• Verfasst von: Heeg, Klaus [VerfasserIn]
• Verfasst von: Boutin, Sébastien [VerfasserIn]
• Verfasst von: Nurjadi, Dennis [VerfasserIn]
• Titel: Pitfalls in genotypic antimicrobial susceptibility testing caused by low expression of blaKPC in Escherichia coli
• Verf.angabe: Kaan Kocer, Sabrina Klein, Dagmar Hildebrand, Johannes Krall, Klaus Heeg, Sébastien Boutin, Dennis Nurjadi
• E-Jahr: 2021
• Jahr: 29 July 2021
• Umfang: 7 S.
• Fussnoten: Gesehen am 28.01.2022
• Titel Quelle: Enthalten in: The journal of antimicrobial chemotherapy
• Ort Quelle: Oxford : Oxford Univ. Press, 1975
• Jahr Quelle: 2021
• Band/Heft Quelle: 76(2021), 11, Seite 2795-2801
• ISSN Quelle: 1460-2091
• DOI: doi:10.1093/jac/dkab267
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 178738182X

Abstract

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.