SINGLE DAILY CEFTRIAXONE AND TOBRAMYCIN IN THE EMPIRICAL MANAGEMENT OF FEBRILE NEUTROPENIC PATIENTS - A RANDOMIZED 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 neutrop enic patients with haematologic disorders (absolute neutrophil count < 1 x 10(9)/l). Upon the development of signs of sepsis, patients recei ved either single daily dose tobramycin (5 mg/kg per day) plus ceftria xone (2 g/day) (C + T, n = 47) or tobramycin (1.5 mg/kg, every 8 h) pl us azlocillin (4 g, every 6 h) (A + T, n = 45). In addition, flucloxac illin (1-2 g, every 4 h) could be added if there was clinical suspicio n of staphylococcal infection (17 in each arm). Analysis was performed for the whole group and for the subset which did not receive flucloxa cillin. When evaluated at 96 h, 62% of patients randomised to C + T an d 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 co mpared with the conventional (multi-daily dose) arm. Within 10 days of antibiotic commencement there was 1 death in the C + T arm and 4 deat hs in the A + T arm, although overall there were 4 deaths in each arm. Our results suggest that single daily empirical antibiotic therapy wi th tobramycin and ceftriaxone is efficacious and is not associated wit h an increased incidence of renal dysfunction or electrolyte imbalance compared with conventional administration schedules of azlocillin plu s tobramycin. Single daily therapy has the potential to lead to saving s in nursing-staff time and materials and may well contribute to an im proved quality of life for febrile neutropenic patients.