A RANDOMIZED DOSAGE STUDY OF CEFTAZIDIME WITH SINGLE DAILY TOBRAMYCINFOR THE EMPIRICAL MANAGEMENT OF FEBRILE NEUTROPENIA IN PATIENTS WITH HEMATOLOGICAL DISEASES

A single-institution, randomised trial was conducted to compare the cl inical and microbiological efficacy of two different doses of ceftazid ime in combination with a single daily dose of tobramycin for the empi rical management of febrile neutropenic patients with hematologic diso rders (absolute neutrophil count < 1 x 10(9)/1). Upon the development of fever or signs of sepsis, patients received either 2 g ceftazidime every 8 h plus a single daily dose tobramycin (5 mg/kg/day) C2T, n = 7 3) or 1 g ceftazidime every 8 h plus a single daily dose of tobramycin (C1T, n = 77). In addition, flucloxacillin (1-2 g every 4 h) could be added if there was clinical suspicion of staphylococcal infection. An alysis was performed for the whole group and for the subset which did not receive flucloxacillin. When evaluated at 96 h, 70% (95% CI, +/- 1 1%) of patients randomised to C2T and 60% (95% CI, +/- 11%) randomised to C1T had responded (chi2 = 1.27, P = 0.26). The response rates at 9 6 h for those who did not receive flucloxacillin were 77% (+/- 12%) an d 74% (+/- 13%), respectively (chi2 = 0.01, P = 0.92). Overall, 68 (93 % +/- 6%) and 72 (94% +/- 6%) patients, respectively, eventually becam e afebrile (chi2 = 0.06, P = 0.81). Rental function, as judged by seru m creatinine, was unaffected by either antibiotic schedule. Within 10 days of antibiotic commencement there was one death in each arm and ov erall there were five deaths in each arm. Our results demonstrate that the combination of 1 g ceftazidime every 8 h combined with a single d aily dose of tobramycin would appear to be as efficacious as 2 g cefta zidime every 8 h plus tobramycin in the empirical management of febril e neutropenic patients with hematological disorders.