title: Ertapenem resistance among extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae isolates.
abstract: Ertapenem resistance in Klebsiella pneumoniae is rare. We report on an ertapenem-nonsusceptible phenotype among 25 out of 663 (3.77%) extended-spectrum-beta-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.
authors.affiliation: Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Azita
authors.initials: A
authors.lastname: Leavitt
authors.forename: Inna
authors.initials: I
authors.lastname: Chmelnitsky
authors.forename: Raul
authors.initials: R
authors.lastname: Colodner
authors.forename: Itzhak
authors.initials: I
authors.lastname: Ofek
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Carmeli
authors.forename: Shiri
authors.initials: S
authors.lastname: Navon-Venezia
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D015373:Bacterial Typing Techniques; D004591:Electrophoresis, Polyacrylamide Gel; D000077727:Ertapenem; D005838:Genotype; D006761:Hospitals; D006801:Humans; D007557:Israel; D007710:Klebsiella Infections / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000145:classification / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D008826:Microbial Sensitivity Tests; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D047090:beta-Lactams; D001618:beta-Lactamases; D000077727:Ertapenem