Cefepime : The Last Generation or the First Enhanced-Potency Broad Spectrum Cephalosporin?

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.