CIPROFLOXACIN VERSUS TRIMETHOPRIM-SULFAMETHOXAZOLE FOR PROPHYLAXIS OF BACTERIAL-INFECTIONS IN BONE-MARROW TRANSPLANT RECIPIENTS - A RANDOMIZED, CONTROLLED TRIAL

Purpose: To compare the efficacy and safety of ciprofloxacin (CIP) and trimethoprim/sulfamethoxazole (TMS) for the prevention of bacteriol infections in patients who received bone marrow transplantation (BMT) for the treatment of solid and hematopoietic neoplasms. Patients and Methods: Adult inpatients about to undergo BMT for lymphoma, leukemia, or solid tumors were enrolled onto a prospective, randomized, double-blinded, controlled trial that compared CIP (750 mg orally twice per day) with TMS (160 mg trimethoprim and 800 mg sulfamethoxazole orally twice per day). Subjects were stratified before randomization according to tumor and BMT type. Prophylaxis was begun within 96 hours of initiation of the BMT preparative regimen and continued until the onset of fever, signs or symptoms of infection, serious adverse effects, or recovery of the absolute granulocyte count (AGC) to greater than or equal to 400/mu L. Results: Seventy-five CIP recipients and 71 TMS recipients were assessable for efficacy. No difference was noted between the two groups in occurrence of fever during neutropenia, time to onset of first fever, or overall infection rates. Ten bacteremias occurred in CIP recipients versus six in TMS recipients (P = .43). Ten episodes of Clostridium difficile enterocolitis occurred in TMS recipients versus no episodes in CIP recipients (P = .001). Four infections caused by gram-negative bacilli, including one bacteremia, occurred in TMS recipients versus none in CIP recipients (P = .06). No differences were noted in the incidence of rash or organ toxicity. TMS recipients had ranger durations of granulocytopenia at AGC levels less than or equal to 500/mu L and less than or equal to 100/mu L than did CIP recipients (P = .08 for both comparisons). Mean peak and trough serum levels of CIP decreased significantly between weeks 1 and 2 of prophylaxis. Conclusion: CIP and TMS were equally safe and effective in the prevention of bacterial infections in BMT patients when the overall infection rate was used as the principal end point. TMS prophylaxis was associated with a higher incidence of C difficile enterocolitis and infections caused by gram-negative bacilli, as well as a trend toward prolongation of granulocytopenia. (C) 1995 by American Society of Clinical Oncology.