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JAC Advance Access originally published online on January 20, 2009
Journal of Antimicrobial Chemotherapy 2009 63(3):427-437; doi:10.1093/jac/dkn547
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Characterization of blaKPC-containing Klebsiella pneumoniae isolates detected in different institutions in the Eastern USA

Andrea Endimiani1,2, Andrea M. Hujer1, Federico Perez3, Christopher R. Bethel1, Kristine M. Hujer1,2, Jennifer Kroeger4, Margret Oethinger5, David L. Paterson6, Mark D. Adams7, Michael R. Jacobs8, Daniel J. Diekema4, Gerri S. Hall5, Stephen G. Jenkins9, Louis B. Rice1, Fred C. Tenover10 and Robert A. Bonomo1,11,12,*

1 Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, 10701 East Boulevard, Cleveland, OH 44106, USA 2 Department of Medicine, Case School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA 3 Division of Infectious Diseases and HIV Medicine, University Hospitals Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA 4 University of Iowa Healthcare, 200 Hawkins Dr, Iowa City, IA 52242, USA 5 Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA 6 University of Pittsburgh Medical Center, 3601 Fifth Avenue, Pittsburgh, PA 15212, USA 7 Department of Genetics, Case School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA 8 Department of Pathology, Case School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA 9 New York-Presbyterian Hospital/Weill Cornell Medical Center, 525 E. 68th Street, Starr 737A, New York City, NY 10029, USA 10 Office of Antimicrobial Resistance, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA 11 Department of Pharmacology, Case School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA 12 Department of Molecular Biology and Microbiology, Case School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA

Received 3 October 2008; returned 5 November 2008; revised 1 December 2008; accepted 12 December 2008

* Corresponding author. Tel: +1-216-7913800 ext. 4399; Fax: +1-216-2313482; E-mail: robert.bonomo{at}med.va.gov

Background: The emergence of blaKPC-containing Klebsiella pneumoniae (KPC-Kp) isolates is attracting significant attention. Outbreaks in the Eastern USA have created serious treatment and infection control problems. A comparative multi-institutional analysis of these strains has not yet been performed.

Methods: We analysed 42 KPC-Kp recovered during 2006–07 from five institutions located in the Eastern USA. Antimicrobial susceptibility tests, analytical isoelectric focusing (aIEF), PCR and sequencing of bla genes, PFGE and rep-PCR were performed.

Results: By in vitro testing, KPC-Kp isolates were highly resistant to all non-carbapenem β-lactams (MIC90s ≥ 128 mg/L). Among carbapenems, MIC50/90s were 4/64 mg/L for imipenem and meropenem, 4/32 mg/L for doripenem and 8/128 for ertapenem. Combinations of clavulanate or tazobactam with a carbapenem or cefepime did not significantly lower the MIC values. Genetic analysis revealed that the isolates possessed the following bla genes: blaKPC-2 (59.5%), blaKPC-3 (40.5%), blaTEM-1 (90.5%), blaSHV-11 (95.2%) and blaSHV-12 (50.0%). aIEF of crude β-lactamase extracts from these strains supported our findings, showing β-lactamases at pIs of 5.4, 7.6 and 8.2. The mean number of β-lactamases was 3.5 (range 3–5). PFGE demonstrated that 32 (76.2%) isolates were clonally related (type A). Type A KPC-Kp isolates (20 blaKPC-2 and 12 blaKPC-3) were detected in each of the five institutions. rep-PCR showed patterns consistent with PFGE.

Conclusions: We demonstrated the complex β-lactamase background of KPC-Kp isolates that are emerging in multiple centres in the Eastern USA. The prevalence of a single dominant clone suggests that interstate transmission has occurred.

Keywords: carbapenemases , ESBLs , Enterobacteriaceae , PFGE , rep-PCR


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