Single daily ceftriaxone and tobramycin in the empirical management of febrile neutropenic patients: a randomised trial.

A single-institution, randomised pilot trial was conducted to compare the clinical efficacy, microbiological efficacy and possible toxicity of empirical single daily antibiotic administration in febrile neutropenic patients with haematologic disorders (absolute neutrophil count < 1 x 10(9)/l). Upon the development of signs of sepsis, patients received either single daily dose tobramycin (5 mg/kg per day) plus ceftriaxone (2 g/day) (C + T, n = 47) or tobramycin (1.5 mg/kg, every 8 h) plus azlocillin (4 g, every 6 h) (A + T, n = 45). In addition, flucloxacillin (1-2 g, every 4 h) could be added if there was clinical suspicion of staphylococcal infection (17 in each arm). Analysis was performed for the whole group and for the subset which did not receive flucloxacillin. When evaluated at 96 h, 62% of patients randomised to C + T and 67% randomised to A + T had responded (95% confidence interval (CI) for the difference in rates, -25% to +15%). Ninety-six hour response rates for those who did not receive flucloxacillin were 73% and 78%, respectively (95% CI, -17% to +27%). Overall, 42 (89%) and 41 (91%) patients, respectively, eventually became afebrile (95% CI, -14 to 10%) and there was no evidence of altered renal function or electrolyte imbalance in patients randomised to single daily antibiotic therapy compared with the conventional (multi-daily dose) arm. Within 10 days of antibiotic commencement there was 1 death in the C + T arm and 4 deaths in the A + T arm, although overall there were 4 deaths in each arm. Our results suggest that single daily empirical antibiotic therapy with tobramycin and ceftriaxone is efficacious and is not associated with an increased incidence of renal dysfunction or electrolyte imbalance compared with conventional administration schedules of azlocillin plus tobramycin. Single daily therapy has the potential to lead to savings in nursing-staff time and materials and may well contribute to an improved quality of life for febrile neutropenic patients.