Single-daily ceftriaxone plus amikacin versus thrice-daily ceftazidime plus amikacin as empirical treatment of febrile neutropenia in children with cancer

Objective: Empirical antibiotic treatment for febrile neutropenic patients has been the mainstay of treatment for many years. Beta-lactam antibiotics and aminoglycosides have been the most frequently used drug combination. Th e purpose of this study was to evaluate the efficacy, safety, tolerance and costs of single-daily ceftriaxone plus amikacin versus thrice-daily dose o f ceftazidime plus amikacin. Methodology: One hundred and ninety-one episodes of fever and neutropenia i n 128 patients from October 1997 to December 1998 were included in a prospe ctive, open-label, single-centre study. Patients were randomly assigned to either treatment group and evaluated as successes or failures according to defined criteria. Daily assessments were made on all patients and all adver se events recorded. Univariate and multivariate analysis of outcomes and a cost analysis were carried out. Results: There were 176 evaluable patient-episodes with 51.1% in the single -daily ceftriaxone-amikacin group and 48.9% in the ceftazidime-amikacin gro up. There were 50 positive blood cultures: 12 Gram-positive bacteria, 33 Gr am-negative bacteria and five fungi. Pseudomonas aeruginosa (P. aeruginosa) accounted for 14% of total isolates. The overall success rate was 55.5% in the ceftriaxone group compared to 51.2% in the ceftazidime group (P = 0.56 ). Mean time to defervescence was 4.2 days in the single-daily group and 4. 3 days in the thrice-dairy group. There were nine infection-related deaths; five in the single-daily ceftriaxone group. The daily cost of the once-dai ly regime was 42 Malaysian Ringgit less than the thrice-daily regime. There was a low incidence of adverse effects in both groups, although ototoxicit y was not evaluable. Conclusions: The once-daily regime of ceftriaxone plus amikacin was as effe ctive as the 'standard' combination of thrice-daily ceftazidime and amikaci n with no significant adverse effects in either group. The convenience and substantial cost benefit of the once-daily regime will be particularly usef ul in developing countries with limited health resources and in centres wit h a low prevalence of P. aeruginosa.