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Microb Drug Resist. 2019 Jan 24. doi: 10.1089/mdr.2018.0263. [Epub ahead of print]

Evaluation of Susceptibilities to Carbapenems and Faropenem Against Cephalosporin-Resistant Neisseria gonorrhoeae Clinical Isolates with penA Mosaic Alleles.

Author information

1
1 Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
2
2 Department of Infection Control and Laboratory Medicine, and Sapporo Medical University School of Medicine, Sapporo, Japan.
3
3 Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
4
4 Division of Laboratory Medicine, Sapporo Medical University Hospital, Sapporo, Japan.
5
5 Division of Bioresources, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan.
6
6 Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan.

Abstract

Neisseria gonorrhoeae is a principal pathogen for sexually transmitted infections, especially for male urethritis. Currently, the prevalence of multidrug resistance is increasing. Carbapenems are broad-spectrum antimicrobials that are widely used in the clinical setting, especially for multidrug-resistant Gram-negative bacteria. However, susceptibility to carbapenems has not been well evaluated for cephalosporin-resistant N. gonorrhoeae isolates. In this study, we determined the susceptibility to a series of carbapenems (meropenem, imipenem, doripenem, and biapenem) and faropenem against cephalosporin-resistant (resistant to cefixime, but susceptible to ceftriaxone) and cephalosporin-susceptible N. gonorrhoeae clinical isolates. The gene mutations associated with β-lactam resistance were evaluated. All cephalosporin-resistant N. gonorrhoeae isolates possessed mosaic mutation alleles in penA (NG-STAR penA-10.001, 27.001, or 108.001). They exhibited a low minimum inhibitory concentration (MIC) (≤0.125 mg/L) for meropenem and markedly high MICs (0.5-2 mg/L) for other carbapenems and faropenem. The strongest association was observed between the mosaic alleles in penA and decreased susceptibility to carbapenems and faropenem compared with mutations in mtrR, porB, and ponA. These results suggest that meropenem may serve as an alternative therapeutic agent for cephalosporin-resistant N. gonorrhoeae with a mosaic allele in penA, whereas other carbapenems and faropenem may be ineffective.

KEYWORDS:

; antimicrobial susceptibility; carbapenem; meropenem; penicillin binding protein

PMID:
30676251
DOI:
10.1089/mdr.2018.0263

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