High-Level Carbapenem Resistance in OXA-232-Producing Raoultella ornithinolytica Triggered by Ertapenem Therapy

Alina Iovleva, Roberta T. Mettus, Christi L. McElheny, Marissa P. Griffith, Mustapha M. Mustapha, A. William Pasculle, Ryan K. Shields, Vaughn S. Cooper, Yohei Doi

Research output: Contribution to journalArticle

Abstract

OXA-232 is an OXA-48-group class D β-lactamase that hydrolyzes expanded-spectrum cephalosporins and carbapenems at low levels. Clinical strains producing OXA-232 are sometimes susceptible to carbapenems, making it difficult to identify them in the clinical microbiology laboratory. We describe the development of carbapenem resistance in sequential clinical isolates of Raoultella ornithinolytica carrying in a hospitalized patient, where the ertapenem MIC increased from blaOXA-232 0.5 μg/ml to 512 μg/ml and the meropenem MIC increased from 0.125 μg/ml to 32 μg/ml during the course of ertapenem therapy. Whole-genome sequencing (WGS) analysis identified loss-of-function mutations in ompC and ompF in carbapenem-resistant isolates that were not present in the initial carbapenem-susceptible isolate. Complementation of a carbapenem-resistant isolate with an intact ompF gene resulted in 16- to 32-fold reductions in carbapenem MICs, whereas complementation with intact ompC resulted in a 2-fold reduction in carbapenem MICs. Additionally, blaOXA-232 expression increased 2.9-fold in a carbapenem-resistant isolate. Rapid development of high-level carbapenem resistance in initially carbapenem-susceptible OXA-232-producing R. ornithinolytica under selective pressure from carbapenem therapy highlights the diagnostic challenges in detecting Enterobacteriaceae strains producing this inefficient carbapenemase.

Original languageEnglish
Article numbere01335-19
JournalAntimicrobial agents and chemotherapy
Volume64
Issue number1
DOIs
Publication statusPublished - 01-01-2020

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Carbapenems
Therapeutics
meropenem
Asp(5)-oxytocin
ertapenem
Enterobacteriaceae
Cephalosporins
Microbiology

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Iovleva, A., Mettus, R. T., McElheny, C. L., Griffith, M. P., Mustapha, M. M., William Pasculle, A., ... Doi, Y. (2020). High-Level Carbapenem Resistance in OXA-232-Producing Raoultella ornithinolytica Triggered by Ertapenem Therapy. Antimicrobial agents and chemotherapy, 64(1), [e01335-19]. https://doi.org/10.1128/AAC.01335-19
Iovleva, Alina ; Mettus, Roberta T. ; McElheny, Christi L. ; Griffith, Marissa P. ; Mustapha, Mustapha M. ; William Pasculle, A. ; Shields, Ryan K. ; Cooper, Vaughn S. ; Doi, Yohei. / High-Level Carbapenem Resistance in OXA-232-Producing Raoultella ornithinolytica Triggered by Ertapenem Therapy. In: Antimicrobial agents and chemotherapy. 2020 ; Vol. 64, No. 1.
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Iovleva, A, Mettus, RT, McElheny, CL, Griffith, MP, Mustapha, MM, William Pasculle, A, Shields, RK, Cooper, VS & Doi, Y 2020, 'High-Level Carbapenem Resistance in OXA-232-Producing Raoultella ornithinolytica Triggered by Ertapenem Therapy', Antimicrobial agents and chemotherapy, vol. 64, no. 1, e01335-19. https://doi.org/10.1128/AAC.01335-19

High-Level Carbapenem Resistance in OXA-232-Producing Raoultella ornithinolytica Triggered by Ertapenem Therapy. / Iovleva, Alina; Mettus, Roberta T.; McElheny, Christi L.; Griffith, Marissa P.; Mustapha, Mustapha M.; William Pasculle, A.; Shields, Ryan K.; Cooper, Vaughn S.; Doi, Yohei.

In: Antimicrobial agents and chemotherapy, Vol. 64, No. 1, e01335-19, 01.01.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - High-Level Carbapenem Resistance in OXA-232-Producing Raoultella ornithinolytica Triggered by Ertapenem Therapy

AU - Iovleva, Alina

AU - Mettus, Roberta T.

AU - McElheny, Christi L.

AU - Griffith, Marissa P.

AU - Mustapha, Mustapha M.

AU - William Pasculle, A.

AU - Shields, Ryan K.

AU - Cooper, Vaughn S.

AU - Doi, Yohei

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