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


CONCLUSIONS
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.
Kang
Cheol-In
CI
Departments of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea.
Pai
Hyunjoo
H
Kim
Sung-Han
SH
Kim
Hong-Bin
HB
Kim
Eui-Chong
EC
Oh
Myoung-don
MD
Choe
Kang-Won
KW
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D000077723:Cefepime; D002511:Cephalosporins / Q000494:pharmacology*; D015169:Colony Count, Microbial; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D008826:Microbial Sensitivity Tests / Q000379:methods; D010957:Plasmids / Q000235:genetics*; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*; D047090:beta-Lactams / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; D047090:beta-Lactams; D000077723:Cefepime; C048795:AmpC beta-lactamases; D001618:beta-Lactamases