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Prompt treatment with empirical antibiotics in neutropenic febrile patients reduces morbidity and mortality. Most patients have been treated with parenteral combination antibiotics, but newer antibiotics with broad-spectrum bactericidal activity have made monotherapy feasible. Ofloxacin, a broad-spectrum fluoroquinolone, has the additional advantage that bactericidal concentrations can be achieved with oral administration. We have compared ofloxacin as an oral single agent with standard parenteral combination antibiotics for the management of neutropenic febrile patients in a prospective, randomised trial. Patients with severe neutropenia (absolute neutrophil count less than or equal to 0.5 x 10(9)/l), fever above 38 degrees C, and ability to take drugs by mouth were eligible for the study. After initial investigations, 60 patients were randomly assigned to oral ofloxacin 400 mg twice daily and 62 to parenteral combination antibiotic therapy (amikacin 15 mg/kg daily, plus, at various times in the trial, carbenicillin, cloxacillin, or piperacillin). Patients were examined 72 h and 7 days after the start of treatment and when neutropenia resolved. 24 (40%) ofloxacin-treated and 26 (42%) combination-treated patients had pyrexia of unknown origin (PUO). In both treatment groups, the treatment success rate was higher for such patients than for those with clinically or microbiologically documented infections (92% vs 67% [p less than 0.05] for ofloxacin; 85% vs 64% for combination). There were no significant differences in success rates of ofloxacin and combination treatment for these subgroups or overall (77% vs 73%). Patients with neutropenia for less than 1 week had better responses to both treatments than patients with longer-lasting neutropenia. There were 4 (7%) deaths in the ofloxacin group and 6 (10%) in the combination group. Both regimens were well tolerated. We conclude that oral single-agent ofloxacin is as effective as parenteral combination antibiotic therapy in neutropenic febrile patients, especially those expected to have short durations of neutropenia.