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JAC Advance Access originally published online on October 14, 2004
Journal of Antimicrobial Chemotherapy 2004 54(6):1130-1133; doi:10.1093/jac/dkh462
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JAC vol.54 no.6 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved

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

Cheol-In Kang1, Hyunjoo Pai2, Sung-Han Kim1, Hong-Bin Kim1, Eui-Chong Kim3,4, Myoung-don Oh1,4,* and Kang-Won Choe1,4

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

* Correspondence address. Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110–744, Republic of Korea. Tel: +82-2-760-2945; Fax: +82-2-762-9662; Email: mdohmd{at}snu.ac.kr

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 ß-lactam agents in standard and high inoculum MIC tests.

Methods: A total of 61 K. pneumoniae blood isolates, including 28 isolates producing AmpC-type ß-lactamases (14 isolates of DHA-1 and 14 isolates of CMY-1-like) and 33 isolates producing extended-spectrum ß-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 ß-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 ß-lactamase-producing K. pneumoniae.

Keywords: K. pneumoniae , cephalosporins , ß-lactam resistance


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