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Meropenem Versus Ceftazidime in the Treatment of Cancer Patients With Febrile Neutropenia: A Randomized, Double-Blind Trial

From the Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada; the University Hospital St Radboud, Nijmegen, the Netherlands; St Francis Medical Center, Honolulu, HI; and St Joseph Hospital, Orange, CA.

Address reprint requests to Ronald Feld, MD, Ontario Cancer Institute, Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9; email ronald.feld{at}uhn.on.ca

PURPOSE: To compare meropenem, a carbapenem antibiotic, with ceftazidime for the empirical treatment of patients with febrile neutropenia.

PATIENTS AND METHODS: A prospective, double-blind, randomized clinical trial was conducted at medical centers in North America and the Netherlands. A total of 411 cancer patients (196 treated with meropenem and 215 treated with ceftazidime), who had 471 episodes of fever, participated in the trial. For each neutropenic episode, patients were allocated at random to receive intravenous administration of meropenem (1 g every 8 hours) or ceftazidime (2 g every 8 hours). Treatment could be modified at any time. Key end points were clinical and bacteriologic outcomes, eradication of infecting organism, and adverse events.

RESULTS: The rate of successful clinical response at the end of therapy was significantly higher for patients treated with meropenem than for those on ceftazidime for all episodes (54% v 44%, respectively) and for episodes of fever of unknown origin (62% v 46%, respectively), but differences between groups were not statistically significant for clinically defined or microbiologically defined infections. Meropenem was significantly more effective than ceftazidime in severely neutropenic ( 100 cells/µL) patients (55% v 43%, respectively), bone marrow transplant patients (73% v 27%, respectively), and patients given antibiotic prophylaxis before study entry (71% v 52%, respectively). Common adverse effects of meropenem and ceftazidime therapy were rash, diarrhea, and nausea and vomiting.

CONCLUSION: Monotherapy with meropenem represents a suitable choice for initial empirical antibiotic therapy for febrile episodes in neutropenic cancer patients.

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