TY  - JOUR
A1  - Hamprecht, Axel
A1  - Sattler, Janko
A1  - Noster, Janina
A1  - Stelzer, Yvonne
A1  - Fuchs, Frieder
A1  - Dorth, Vivien
A1  - Gatermann, Sören
A1  - Göttig, Stephan
T1  - Proteus mirabilis – analysis of a concealed source of carbapenemases and development of a diagnostic algorithm for detection
T2  - Clinical Microbiology and Infection
N2  - 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.
KW  - Carbapenemase
KW  - CIM
KW  - Detection
KW  - OXA-23
KW  - OXA-48
KW  - OXA-58
Y1  - 2023
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/79011
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-790116
SN  - 1198-743X
VL  - 29
IS  - 9
SP  - 1198.e1
EP  - 1198.e6
PB  - Elsevier
CY  - Amsterdam
ER  -