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JAC Advance Access published online on October 14, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh462
© 2004 by The British Society for Antimicrobial Chemotherapy
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Received July 10, 2004
Revised September 5, 2004
Accepted September 14, 2004

Brief report

Cefepime and the inoculum effect in tests with Klebsiella pneumoniae producing plasmid-mediated AmpC-type {beta}-lactamase

Cheol-In Kang 1, Hyunjoo Pai 2, Sung-Han Kim 1, Hong-Bin Kim 1, Eui-Chong Kim 3, Myoung-don Oh 4*, and Kang-Won Choe 5

1 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
2 Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
3 Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
4 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
5 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea

* To whom correspondence should be addressed. E-mail: mdohmd{at}snu.ac.kr.


  Abstract

Objective: In the past decade, a new problem in Klebsiella pneumoniae strains has emerged: plasmid-mediated AmpC enzymes. This study was conducted to investigate the activity of cefepime against clinical isolates by determining the activities of cefepime and three other parenteral {beta}-lactam agents in standard and high inoculum MIC tests.

Methods: A total of 61 K. pneumoniae blood isolates, including 28 isolates producing AmpC-type {beta}-lactamases (14 isolates of DHA-1 and 14 isolates of CMY-1-like) and 33 isolates producing extended-spectrum {beta}-lactamases (ESBLs) (32 isolates of TEM- or SHV-related and one isolate of CTX-M-14-like), were included in the study. Antimicrobial susceptibilities were determined using broth microdilution MIC tests with standard and 100-fold-higher inocula. The inoculum effect was defined as an eight-fold or greater MIC increase on testing with the higher inoculum.

Results: In tests with AmpC {beta}-lactamase-producing K. pneumoniae isolates and their transconjugants, the inoculum effect was most consistently detected with cefepime, cefotaxime and ceftazidime, as inoculum effects were consistently detected in ESBL-producing isolates. However, the inoculum effect was least frequently detected with imipenem.

Conclusion: Although the inoculum effect is an in vitro laboratory phenomenon, these results suggest that cefepime may be a less than reliable agent for therapy in cases of high inoculum infections caused by AmpC {beta}-lactamase-producing K. pneumoniae.

Keywords: K. pneumoniae; cephalosporins; {beta}-lactam resistance.
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