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Cefepime : The Last Generation or the First Enhanced-Potency Broad Spectrum Cephalosporin?
1Department of Medical Microbiology, Creighton University School of Medicine, 2500 California Plaza, Omaha, Nebraska, 68178, USA.
Abstract:
Cefepime and 8 other β-lactam antibiotics were compared with regard to in vitro activity against 134 clinical isolates of Gram-negative bacteria resistant to β-lactam antibiotics by a variety of mechanisms. Overall, cefepime was the most active cephalosporin tested, inhibiting 104 of 112 (93%) strains of Enterobacteriaceae and 12 of 22 (55%) strains of Pseudomonas aeruginosa at concentrations of 8 mg/L or less. In contrast, ceftazidime inhibited only 64 (57%) of the Enterobacteriaceae and 11 (50%) of the P. aeruginosa strains. Imipenem was the most active β-lactam agent tested, although some strains resistant to the carbapenem were susceptible to cefepime. Cefepime was less likely than ceftazidime to select mutants from organisms possessing inducible Bush Group 1 β-lactamases. Of 19 mutants selected by various cephalosporins, 18 (95%) remained susceptible to cefepime, whereas only 6 (32%) were susceptible to ceftazidime. These findings suggest that cefepime possesses enhanced activity compared with other cephalosporins, and this may result from its improved penetration into the Gram-negative cell and the lower affinity of β-lactamases for the drug.
Insights
Cefepime demonstrated superior in vitro activity against Gram-negative bacteria compared to other cephalosporins. It effectively inhibited resistant strains, showing enhanced efficacy and reduced resistance selection.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Gram-negative bacterial resistance to beta-lactam antibiotics is a growing clinical concern.
- Various resistance mechanisms, including beta-lactamases, contribute to treatment challenges.
Purpose of the Study:
- To compare the in vitro activity of cefepime against other beta-lactam antibiotics.
- To evaluate the efficacy of cefepime against Gram-negative bacteria with diverse resistance mechanisms.
Main Methods:
- In vitro susceptibility testing of 134 clinical isolates of Gram-negative bacteria.
- Comparison of cefepime, ceftazidime, and imipenem against Enterobacteriaceae and Pseudomonas aeruginosa.
- Assessment of cefepime's ability to select for resistant mutants.
Main Results:
- Cefepime exhibited high activity against Enterobacteriaceae (93%) and moderate activity against Pseudomonas aeruginosa (55%) at ≤8 mg/L.
- Cefepime was more active than ceftazidime against both bacterial groups.
- Imipenem showed the highest overall activity, but some carbapenem-resistant strains remained susceptible to cefepime.
- Cefepime was less likely to select for resistant mutants compared to ceftazidime.
Conclusions:
- Cefepime possesses enhanced in vitro activity compared to other cephalosporins against resistant Gram-negative bacteria.
- Improved Gram-negative cell penetration and lower affinity for beta-lactamases may contribute to cefepime's efficacy.
- Cefepime represents a valuable therapeutic option for infections caused by resistant Gram-negative pathogens.
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