Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy

Background Intravenously administered antimicrobial agents have been the st andard choice for the empirical management of fever in patients with cancer and granulocytopenia. If orally administered empirical therapy is as effec tive as intravenous therapy, it would offer advantages such as improved qua lity of life and lower cost. Methods In a prospective, open-label, multicenter trial, we randomly assign ed febrile patients with cancer who had granulocytopenia that was expected to resolve within 10 days to receive empirical therapy with either oral cip rofloxacin (750 mg twice daily) plus amoxicillin-clavulanate (625 mg three times daily) or standard daily doses of intravenous ceftriaxone plus amikac in. All patients were hospitalized until their fever resolved. The primary objective of the study was to determine whether there was equivalence betwe en the regimens, defined as an absolute difference in the rates of success of 10 percent or less. Results Equivalence was demonstrated at the second interim analysis, and th e trial was terminated after the enrollment of 353 patients. In the analysi s of the 312 patients who were treated according to the protocol and who co uld be evaluated, treatment was successful in 86 percent of the patients in the oral-therapy group (95 percent confidence interval, 80 to 91 percent) and 84 percent of those in the intravenous-therapy group (95 percent confid ence interval, 78 to 90 percent; P=0.02). The results were similar in the i ntention-to-treat analysis (80 percent and 77 percent, respectively; P=0.03 ), as were the duration of fever, the time to a change in the regimen, the reasons for such a change, the duration of therapy, and survival. The types of adverse events differed slightly between the groups but were similar in frequency. Conclusions In low-risk patients with cancer who have fever and granulocyto penia, oral therapy with ciprofloxacin plus amoxicillin-clavulanate is as e ffective as intravenous therapy. (N Engl J Med 1999; 341:312-8.) (C) 1999, Massachusetts Medical Society.