Cefepime: overview of activity in vitro and in vivo

Abstract

Cefepime is a novel methoxyimino-aminothiazolyl cephalosporin with a quaternized N-methyl-pyrrolidine moiety at the 3' position conferring zwitterionic properties. Because of this the molecule penetrates the outer cell membrane of Gram-negative bacteria rapidly. In addition it is resistant to degradation by several plasmid and chromosomally-mediated beta-lactamases, for which it also shows very low affinity and no inducing capacity. It has good affinity for PBPs 2 and 3 of Escherichia coli and for PBP 3 of Pseudomonas aeruginosa. Its broad-spectrum of activity includes Gram-positive and Gram-negative pathogens. It is more active than cefotaxime or ceftazidime, against Enterobacteriaceae. The MIC90 for P. aeruginosa is higher than that of ceftazidime, but lower than those of cefpirome, cefoperazone and latamoxef. Other Gram-negative organisms, Haemophilus influenzae, Neiserria meningitidis, Neiserria gonorrhoeae, Moraxella catarrhalis are highly susceptible to cefepime. Among Gram-positive species methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci, whether beta-lactamase producers or not, Streptococcus pneumoniae and Streptococcus pyogenes are susceptible. Cefepime is active against cefotaxime- and/or ceftazidime-resistant Enterobacteriaceae. Only strains of P. aeruginosa producing large amounts of beta-lactamase may be resistant to both ceftazidime and cefepime. In experimental infections such as meningitis, induced with various bacterial species in neonatal rats and chronic staphylococcal osteomyelitis in rabbits, cefepime has shown good efficacy.

Decreasing antibiotic resistance of Enterobacteriaceae by introducing a new antibiotic combination therapy for neutropenic fever patients

“…Cefepime is, in vitro, active against ceftazidime-resistant Enterobacteriaceae. 12 Second, combination therapy with amikacin could act synergistically against Gram-negative bacteria. That the combination of amikacin and cefepime at least partly played a role in reducing the reduced susceptibility rate of inducible Enterobacteriaceae, can be deduced from the observation that the amikacin reduced susceptibility rate also dropped, as compared to a period where this antibiotic was not routinely used as a first-line medication for neutropenic fever.…”

Determination of cefepime in plasma and cerebrospinal fluid by micellar electrokinetic chromatography with direct sample injection

“…Cefepime has a broad spectrum in activity that encompasses a wide range of Gram-positive and Gram-negative bacteria, including strains resistant to aminoglycosides or third-generation cephalosporins. On the other hand, cefepime has a low affinity for b-lactamases so it is very effective against many b-lactamase-producing strains [1][2][3][4][5][6]. Cefepime is indicated for respiratory tract infections, skin and soft-tissue infections, urinary tract infections, febrile neutropenia [5,6], and intra-abdominal infections.…”

Clinical Pharmacodynamics of Antipseudomonal Cephalosporins in Patients with Ventilator-Associated Pneumonia

“…Ceftazidime and cefepime are advanced-generation cephalosporins with activity against a broad spectrum of Gram-positive and Gram-negative aerobic bacteria, including Pseudomonas aeruginosa and Enterobacteriaceae (3,4,5,6,7). As a result, these agents are routinely prescribed for empirical coverage of many severe infections and are recommended as a backbone empirical therapy in the current VAP guidelines (8).…”