In a pilot study, we evaluated the efficacy and the safety of
cefepime, a new
cephalosporin with extended-spectrum activity against both Gram-positive and Gram-negative bacteria, as empirical monotherapy for 108 febrile episodes in 84 granulocytopenic
cancer patients.
Cefepime (2 g
tds) was given for a minimum of 7 days or until resolution of
infection. Of the 108 episodes, 91 were evaluable. Microbiologically documented
infections occurred in 25 patients (27%) (18 Gram-positive, 7 Gram-negative), of whom 18 had bacteraemia.
Infection was clinically documented in 47 patients (52%) and
fever was unexplained in 19 (21%). Overall, 71% (65/91) of the
infections resolved. Response rates were 86% (6/7) for Gram-negative
infections, 44% (8/18) for Gram-positive
infections (57% for
cefepime-susceptible Gram-positive bacteria), 77% (36/47) for clinically documented
infections and 79% (15/19) for unexplained
fevers. Of the 26 patients (29%) whose primary
infections did not improve with
cefepime monotherapy, 23 responded after the addition of other
antibiotics. Sixteen patients (18%) developed
secondary infections of which 13 were microbiologically documented; Gram-positive bacteria were isolated from seven patients, Gram-negative bacteria from two, fungi from three and a virus from one. Adverse effects were mild and did not require premature discontinuation of
therapy except for one patient who developed an immediate
allergic reaction after the first dose of
cefepime from which he recovered fully. The survival rate after resolution of
granulocytopenia was 96%; three patients died of primary
bacterial infection and one from secondary disseminated
candidiasis. In this pilot study,
cefepime monotherapy appeared safe and effective as empirical
therapy for
fever in
cancer patients with
granulocytopenia. Whether
cefepime is superior to other advanced-generation
cephalosporins for the treatment of Gram-positive
infections will require evaluation in a larger comparative study.