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Cefepime and the inoculum effect in tests with Klebsiella pneumoniae producing plasmid-mediated AmpC-type
Cheol-In Kang1, Hyunjoo Pai, Sung-Han Kim
1Departments of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea.
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.
Insights
Cefepime effectiveness against Klebsiella pneumoniae strains producing AmpC beta-lactamases is questionable due to the inoculum effect. This in vitro study suggests caution when using cefepime for high-bacterial-load infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Plasmid-mediated AmpC beta-lactamases are an emerging challenge in Klebsiella pneumoniae.
- These enzymes confer resistance to various beta-lactam antibiotics.
Purpose of the Study:
- To evaluate the in vitro activity of cefepime against Klebsiella pneumoniae isolates producing AmpC enzymes.
- To compare cefepime's efficacy with other parenteral beta-lactams under standard and high inoculum conditions.
Main Methods:
- Analyzed 61 K. pneumoniae blood isolates, including AmpC and ESBL producers.
- Determined antimicrobial susceptibilities using broth microdilution with standard and 100-fold-higher inocula.
- Defined inoculum effect as an eight-fold or greater MIC increase with higher inoculum.
Main Results:
- The inoculum effect was most consistently observed with cefepime, cefotaxime, and ceftazidime in AmpC and ESBL-producing K. pneumoniae.
- Imipenem exhibited the least frequent inoculum effect.
- Cefepime showed a notable inoculum effect in ESBL-producing isolates.
Conclusions:
- The inoculum effect, observed in vitro, suggests potential therapeutic limitations for cefepime.
- Cefepime may not be a reliable treatment option for high-inoculum infections caused by AmpC-producing K. pneumoniae.
