Prevention of bacterial infection in neutropenic patients with hematologic malignancies. A randomized, multicenter trial comparing norfloxacin with ciprofloxacin. The GIMEMA Infection Program. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto

Abstract

Objective: To compare the efficacy of norfloxacin and ciprofloxacin in preventing bacterial infection in neutropenic patients.

Design: A randomized, controlled, multicenter trial.

Setting: Twenty-one hematologic units in tertiary care or university hospitals.

Patients: Eight hundred and one consecutive, afebrile, adult patients who had hematologic malignancies or who had bone marrow transplantation and chemotherapy-induced neutropenia (neutrophil count, less than 1000/mm3) expected to last more than 10 days.

Intervention: Patients were randomly assigned to receive orally every 12 hours norfloxacin, 400 mg, or ciprofloxacin, 500 mg.

Measurements: Efficacy analysis was done for 619 patients: 319 treated with norfloxacin and 300 treated with ciprofloxacin.

Main results: More patients receiving ciprofloxacin did not develop fever during neutropenia and did not receive antibiotics (34%) compared with those receiving norfloxacin (25%) (P = 0.01). Patients receiving ciprofloxacin had a lower rate of microbiologically documented infection (17% compared with 24%; P = 0.058), particularly of infection from gram-negative bacilli (4% compared with 9%; P = 0.03). The interval to the first febrile episode was also longer in patients receiving ciprofloxacin (8.3 compared with 7.2 days; P = 0.055). The rates of clinically documented infection, fever of unknown origin, and mortality as well as compliance and tolerability were similar in the two groups. Patients who had neutropenia for less than 15 days, who had severe neutropenia for less than 7 days, and who received antifungal prophylaxis benefited most from ciprofloxacin therapy.

Conclusion: Ciprofloxacin should be used to prevent the development of infection in neutropenic patients with hematologic malignancies.