CEFTAZIDIME COMPARED WITH PIPERACILLIN AND TOBRAMYCIN FOR THE EMPIRICTREATMENT OF FEVER IN NEUTROPENIC PATIENTS WITH CANCER - A MULTICENTER RANDOMIZED TRIAL

Objective: To compare piperacillin and tobramycin with ceftazidime alo ne for the empiric treatment of fever in the neutropenic patient witho ut evidence of skin infections or anaerobic infections. Design: A mult icenter, randomized, controlled trial. Patients: 876 febrile, neutrope nic episodes in 696 patients (83% acute leukemia or bone marrow transp lantation); 92 episodes were excluded from analysis because of protoco l violation. Interventions: Patients received either intravenous cefta zidime (2 g every 8 h) or piperacillin (12 to 18 g/d in 4 to 6 divided doses plus tobramycin (1.7 to 2.0 mg/kg body weight every 8 h). Treat ment could be modified at any time at the discretion of the investigat or. Measurements: Percentage of satisfactory response, eradication of the infecting organism, development of superinfections, and occurrence of adverse events. Results: As a single agent, ceftazidime was as eff ective as the combination of piperacillin and tobramycin (62.7% satisf actory responses compared with 61.1%; odds ratio, 1.07; 95% CI, 0.79 t o 1.44; P > 0.2). Equivalent responses were also obtained in episodes of profound neutropenia (odds ratio, 0.76; CI, 0.43 to 1.33; P > 0.2). Infectious mortality was 6% for ceftazidime and 8% for the combinatio n therapy. Eradication of the infecting organisms was achieved in 79% of bacteremic episodes treated with ceftazidime compared with 68% of t he episodes treated with the combination therapy (odds ratio, 1.76; CI , 0.92 to 3.38; P = 0.08), and rates for gram-negative rod bacteremia were also similar (95% compared with 77%; odds ratio, 5.25; CI, 1.0 to 27.5; P = 0.03). Superinfections developed in 38 episodes in each gro up. An adverse event occurred in 8% of episodes treated with ceftazidi me compared with 20% of episodes treated with combination therapy (P < 0.001). Conclusion: Ceftazidime alone was as effective but safer than the combination of piperacillin and tobramycin for the empiric treatm ent of febrile, neutropenic patients, even those with profound and pro longed granulocytopenia.