A single-institution, randomised trial was conducted to compare the clinical and microbiological efficacy of two different doses of
ceftazidime in combination with a single daily dose of
tobramycin for the empirical management of febrile neutropenic patients with hematologic disorders (absolute neutrophil count < 1 x 10(9)/l). 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 = 73) 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. Analysis was performed for the whole group and for the subset which did not receive
flucloxacillin. When evaluated at 96 h, 70% (95% CI, +/- 11%) of patients randomised to C2T and 60% (95% CI, +/- 11%) randomised to C1T had responded (chi 2 = 1.27, P = 0.26). The response rates at 96 h for those who did not receive
flucloxacillin were 77% (+/- 12%) and 74% (+/- 13%), respectively (chi 2 = 0.01, P = 0.92). Overall, 68 (93% +/- 6%) and 72 (94% +/- 6%) patients, respectively, eventually became afebrile (chi 2 = 0.06, P = 0.81). Renal function, as judged by serum
creatinine, was unaffected by either
antibiotic schedule. Within 10 days of
antibiotic commencement there was one death in each arm and overall there were five deaths in each arm.(ABSTRACT TRUNCATED AT 250 WORDS)