A randomised dosage study of ceftazidime with single daily tobramycin for the empirical management of febrile neutropenia in patients with hematological diseases
Gibson, J.; Johnson, L.; Snowdon, L.; Joshua, D.; Young, G.; MacLeod, C.; Iland, H.; Vincent, P.; Kronenberg, H.
International Journal of Hematology 60(2): 119-127
1994
ISSN/ISBN: 0925-5710 PMID: 7948961 Document Number: 428021
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 lt 1 times 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) (C-2T, n = 73) or 1 g ceftazidime every 8 h plus a single daily dose of tobramycin (C-1T, 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 C-2T and 60% (95% Col, +- 11%) randomised to C-1T 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 = 0.8 1). 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. Our results demonstrate that the combination of 1 g ceftazidime every 8 h combined with a single daily dose of tobramycin would appear to be as efficacious as 2 g ceftazidime every 8 h plus tobramycin in the empirical management of febrile neutropenic patients with hematological disorders.