Proteus mirabilis – analysis of a concealed source of carbapenemases and development of a diagnostic algorithm for detection

  • Objectives: To analyse carbapenemases in Proteus mirabilis and assess the performance of carbapenemase detection assays. Methods: 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. Results: 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. Discussion: 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 blaOXA-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.
Metadaten
Author:Axel HamprechtORCiDGND, Janko SattlerORCiDGND, Janina NosterORCiDGND, Yvonne Stelzer, Frieder FuchsORCiD, Vivien Dorth, Sören GatermannGND, Stephan GöttigORCiDGND
URN:urn:nbn:de:hebis:30:3-790116
DOI:https://doi.org/10.1016/j.cmi.2023.05.032
ISSN:1198-743X
Parent Title (English):Clinical Microbiology and Infection
Publisher:Elsevier
Place of publication:Amsterdam
Document Type:Article
Language:English
Date of Publication (online):2023/08/18
Date of first Publication:2023/06/02
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/02/02
Tag:CIM; Carbapenemase; Detection; OXA-23; OXA-48; OXA-58
Volume:29
Issue:9
Page Number:1197988021
First Page:1198.e1
Last Page:1198.e6
HeBIS-PPN:517874172
Institutes:Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International