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J Antimicrob Chemother. 2004 Dec;54(6):1130-3. Epub 2004 Oct 14.

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

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Departments of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea.



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.


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.


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.


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.

[Indexed for MEDLINE]

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