A randomized trial of single daily dose vancomycin and tobramycin plus oral ciprofloxacin versus standard-dose vancomycin, ceftazidime, and tobramycin in febrile neutropenic recipients of autologous peripheral blood progenitor cell transplants

This study assessed the safety and efficacy of a single-daily dose antibiotic regimen potentially suited to outpatient administration, compared with a triple antibiotic regimen using traditional dosing in febrile neutropenic recipients of autologous peripheral blood progenitor cell transplants. This was a randomized, comparative trial performed in a bone marrow transplant inpatient unit at a 925-bed academic medical center. Eighty patients with breast cancer, Hodgkin's disease, non-Hodgkin's lymphoma, or other cancers receiving autologous peripheral blood progenitor cell transplants were enrolled in the trial. At the time of first episode of neutropenic fever, patients were randomized to receive either CipTV (single-daily-dose vancomycin 1.5 g/d plus single-daily dose tobramycin 5 mg/kg/d plus oral ciprofloxacin 750 mg po BID) versus CefTV (vancomycin 1 g IV q 12h plus tobramycin 2 mg/kg IV load, then 1.4 mg/kg q 8h, plus ceftazidime 1 g IV q 8h). Positive blood cultures, serum creatinine, neutropenic days, total antibiotic days, documented infection, rash, diarrhea, and length of stay all were not significantly different between CipTV and CefTV. There were no deaths in either group. There was a trend toward more febrile days and more changes in regimen in the CipTV group. Changes in dosing were more frequent in the CipTV group (43% vs. 18%, p = 0.02, OR 3.32), largely reflecting change from single-daily to standard dosing. Comparison of CipTV and CefTV showed no significant differences in outcome, but both regimens were changed frequently. In particular, inability to continue oral ciprofloxacin in patients with mucositis, and clinician tendency to seek alternative gram-negative and expanded anaerobic coverage, may make such a regimen impractical for outpatient administration.