Patterns in resistance and cost implications have led the Drug Therapy Committee and the Infectious Disease Division to re-evaluate the currently available third-generation cephalosporins. Ceftazidime will no longer be available for general use. We will be replacing it with cefepime, a fourth-generation cephalosporin, for the treatment of infections for which we have previously recommended ceftazidime, i.e., those in which broad gram-negative coverage to include Pseudomonas aeruginosa is needed. As was the case with ceftazidime, cefepime will require approval by a member of the ID Division. Ceftriaxone, a third-generation cephalosporin, is still available for general use without ID approval. Ceftriaxone lacks activity against P. aeruginosa.

Cefepime is approved as empiric monotherapy for febrile neutropenic patients. Its additional indications include hospital-acquired pneumonia and urinary tract infections due to susceptible Gram-negative pathogens, uncomplicated skin and skin-structure infections, and complicated intra-abdominal infections (when used with metronidazole, with or without ampicillin). Cefepime is not indicated, however, for treatment of meningitis.

Cefepime has improved coverage of some resistant Gram-negative pathogens compared with ceftriaxone and ceftazidime, including coverage of some Enterobacter spp, Serratia spp, Citrobacter spp, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Cefepime, relative to ceftazidime, has better gram-positive coverage (particularly for Streptococcus pneumoniae) and may have a lower potential to promote resistance to third-generation cephalosporins. Cefepime has a similar safety profile to that of the third-generation cephalosporins.

For most infections, cefepime is dosed 1 g intravenously every 12 hours in adult patients with normal renal function; Patients with normal renal function receiving cefepime therapy for febrile neutropenia should be dosed every eight hours.

Pediatric patients can be treated with 50 mg / kg / dose every 12 hours (up to a maximum of 2 grams per day for moderate to severe pneumonia, skin infections and complicated urinary tract and pyleonephritis. For empiric treatment of febrile neutropenia, cefipime should be dosed 50 mg / kg / dose intravenously every 8 hours Doses of cefepime 50 milligrams/kilogram (maximum dose 2 grams) every 8 hours have been used to treat acute bronchopulmonary exacerbations of cystic fibrosis.

Cefipime requires dosage adjustment in renal insufficiency. Dosing in renal failure is summarized below.

The cost of cefepime is similar to that of third-generation cephalosporins. Pharmacoeconomic data suggest that cefepime therapy can provide additional cost savings because concomitant agents such as vancomycin may be used less often as compared to when ceftazidime is used as therapy. Reduced vancomycin use not only will save us money, but also will help to minimize the emergence of vancomycin-resistant enterococci. Additionally, a decreased rate of resistance in gram-negative bacteria may reduce the need for other broad spectrum agents, such as meropenem.

Selected references

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2. Yee YC, Thornsberry C, Brown SD, et al. A comparative study of the in-vitro activity of cefepime and other antimicrobial agents against penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae. J Antimicrob Chemother. 1993;32(suppl B):13-19.
3. Jones RN, Marshall SA. Antimicrobial activity of cefepime tested against Bush group I b -lactamase-producing strains resistant to ceftazidime: a multilaboratory national and international clinical isolate study. Diagn Microbiol Infect Dis. 1994;19:33-38.
4. Gradelski E, Fung-Tomc J, Huczko E, et al. Development of resistance in Pseudomonas aeruginosa to broad-spectrum cephalosporins via step-wise mutations. J Antimicrob Chemother. 1993;32(suppl B):75-80.
5. Sanders CC. Cefepime: the next generation? Clin Infect Dis. 1993;17:369-379.
6. Ambrose PG, Richerson MA, Stanton M-E, et al. Cost-effectiveness analysis of cefepime compared with ceftazidime in intensive care unit patients with hospital-acquired pneumonia. Infect Dis Clin Pract. 1999;8:245-251.