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Journal of Clinical Microbiology, April 2009, p. 969-974, Vol. 47, No. 4
0095-1137/09/$08.00+0     doi:10.1128/JCM.00651-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Ertapenem Resistance among Extended-Spectrum-β-Lactamase-Producing Klebsiella pneumoniae Isolates{triangledown}

Azita Leavitt,1 Inna Chmelnitsky,1 Raul Colodner,2 Itzhak Ofek,3 Yehuda Carmeli,1 and Shiri Navon-Venezia1*

The Laboratory for Molecular Epidemiology and Antibiotic Research, Division of Epidemiology, Tel Aviv Sourasky Medical Center—Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel,1 Clinical Microbiology Laboratory, Ha'Emek Medical Center, Afula, Israel,2 Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel3

Received 7 April 2008/ Returned for modification 19 September 2008/ Accepted 3 February 2009

Ertapenem resistance in Klebsiella pneumoniae is rare. We report on an ertapenem-nonsusceptible phenotype among 25 out of 663 (3.77%) extended-spectrum-β-lactamase (ESBL)-producing K. pneumoniae isolates in a multicenter Israeli study. These isolates originated from six different hospitals and were multiclonal, belonging to 12 different genetic clones. Repeat testing using Etest and agar dilution confirmed ertapenem nonsusceptibility in only 15/663 (2.3%) of the isolates. The molecular mechanisms of ertapenem resistance in seven single-clone resistant isolates was due to the presence of ESBL genes (CTX-M-2 in four isolates, CTX-M-10 and OXA-4 in one isolate, SHV-12 in one isolate, and SHV-28 in one isolate) combined with the absence of OMPK36. Seven of 10 isolates initially reported as ertapenem nonsusceptible and subsequently classified as susceptible showed an inoculum effect with ertapenem but not with imipenem or meropenem. Population analysis detected the presence of an ertapenem-resistant subpopulation at a frequency of 10–6. These rare resistant subpopulations carried multiple ESBL genes, including TEM-30, SHV-44, CTX-M-2, and CTX-M-10, and they lacked OMPK36. The clinical and diagnostic significance of the results should be further studied.

* Corresponding author. Mailing address: Division of Epidemiology, Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv 64239, Israel. Phone: 972 3 692 5644. Fax: 972 3 697 4966. E-mail: shiri_nv{at}tasmc.health.gov.il

{triangledown} Published ahead of print on 11 February 2009.

Journal of Clinical Microbiology, April 2009, p. 969-974, Vol. 47, No. 4
0095-1137/09/$08.00+0     doi:10.1128/JCM.00651-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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