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Journal of Clinical Microbiology, October 2005, p. 5058-5064, Vol. 43, No. 10
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.10.5058-5064.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

SHV-Type Extended-Spectrum Beta-Lactamase Production Is Associated with Reduced Cefepime Susceptibility in Enterobacter cloacae

Dóra Szabó,1,2 Robert A. Bonomo,3 Fernanda Silveira,1 A. William Pasculle,4 Carla Baxter,4 Peter K. Linden,5 Andrea M. Hujer,3 Kristine M. Hujer,3 Kathleen Deeley,1 and David L. Paterson1*

Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213,1 Institute of Medical Microbiology, Semmelweis University, Budapest, Hungary,2 Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio 44106,3 Clinical Microbiology Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213,4 Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 152135

Received 4 June 2005/ Returned for modification 5 July 2005/ Accepted 18 July 2005

Cefepime is a potentially useful antibiotic for treatment of infections with Enterobacter cloacae. However, in our institution the MIC90 for E. cloacae bloodstream isolates is 16 µg/ml. PCR amplification of bla genes revealed that one-third (15/45) of E. cloacae bloodstream isolates produced SHV-type extended-spectrum beta-lactamases (ESBLs) in addition to hyperproduction of AmpC-type beta-lactamases. The majority (11/15) of ESBL producers also produced the TEM-1 beta-lactamase. The SHV types included SHV-2, -5, -7, -12, -14, and -30. All but two of the ESBL-producing E. cloacae isolates, but none of the non-ESBL-producing strains, had MICs of cefepime of ≥2 µg/ml. The MIC90 for cefepime for ESBL-producing strains was 64 µg/ml, while for non-ESBL producers it was 0.5 µg/ml. Using current Clinical and Laboratory Standards Institute breakpoints for cefepime, two thirds (10/15) of ESBL-producing isolates would have been regarded as susceptible to cefepime. Phenotypic ESBL detection methods were generally unreliable with these E. cloacae isolates. Based on these results, pharmacokinetic, pharmacodynamic, and clinical reevaluation of cefepime breakpoints for E. cloacae may be prudent.


* Corresponding author. Mailing address: UPMC Division of Infectious Diseases, Suite 3A Falk Medical Building, 3601 5th Avenue, Pittsburgh, PA 15213. Phone: (412) 648-6478. Fax: (412) 648-6399. E-mail: patersond{at}dom.pitt.edu.


Journal of Clinical Microbiology, October 2005, p. 5058-5064, Vol. 43, No. 10
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.10.5058-5064.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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