A Double-Blind Comparison of Empirical Oral and Intravenous Antibiotic Therapy for Low-Risk Febrile Patients with Neutropenia during Cancer Chemotherapy
Alison Freifeld, M.D., Donna Marchigiani, R.N., Thomas Walsh, M.D., Stephen Chanock, M.D., Linda Lewis, M.D., John Hiemenz, M.D., Sharon Hiemenz, R.N., Jeanne E. Hicks, M.D., Vee Gill, Ph.D., Seth M. Steinberg, Ph.D., and Philip A. Pizzo, M.D.
Background Among patients with fever and neutropenia duringcancer chemotherapy who have a low risk of complications, oraladministration of empirical broad-spectrum antibiotics may bean acceptable alternative to intravenous treatment.
Methods We conducted a randomized, double-blind, placebo-controlledstudy of patients (age, 5 to 74 years) who had fever and neutropeniaduring chemotherapy for cancer. Neutropenia was expected tobe present for no more than 10 days in these patients, and theyhad to have no other underlying conditions. Patients were assignedto receive either oral ciprofloxacin plus amoxicillinclavulanateor intravenous ceftazidime. They were hospitalized until feverand neutropenia resolved.
Results A total of 116 episodes were included in each group(84 patients in the oral-therapy group and 79 patients in theintravenous-therapy group). The mean neutrophil counts at admissionwere 81 per cubic millimeter and 84 per cubic millimeter, respectively;the mean duration of neutropenia was 3.4 and 3.8 days, respectively.Treatment was successful without the need for modificationsin 71 percent of episodes in the oral-therapy group and 67 percentof episodes in the intravenous-therapy group (difference betweengroups, 3 percent; 95 percent confidence interval, 8percent to 15 percent; P=0.48). Treatment was considered tohave failed because of the need for modifications in the regimenin 13 percent and 32 percent of episodes, respectively (P<0.001)and because of the patient's inability to tolerate the regimenin 16 percent and 1 percent of episodes, respectively (P<0.001).There were no deaths. The incidence of intolerance of the oralantibiotics was 16 percent, as compared with 8 percent for placebo(P=0.07).
Conclusions In hospitalized low-risk patients who have feverand neutropenia during cancer chemotherapy, empirical therapywith oral ciprofloxacin and amoxicillinclavulanate issafe and effective.
Source Information
From the National Cancer Institute (A.F., D.M., T.W., S.C., L.L., S.M.S.) and the Warren Grant Magnusen Clinical Center (J.E.H., V.G.), National Institutes of Health, Bethesda, Md.; the H. Lee Moffitt Cancer Center, University of South Florida, Tampa (J.H., S.H.); and Children's Hospital and Harvard Medical School, Boston (P.A.P.).
Address reprint requests to Dr. Freifeld at the University of Nebraska Medical Center, Infectious Diseases Section, 985400 Nebraska Medical Center, Omaha, NE 68198-5400.
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