Once daily ceftriaxone plus amikacin vs. three times daily ceftazidime plus amikacin for treatment of febrile neutropenic children with cancer

Background. The combination of ceftazidime plus aminoglycoside is widely used for the treatment of febrile neutropenic patients but requires multiple daily administration. Because the frequency of Pseudomonas aeruginosa is low in many centers, there is a rationale to test other antibiotic regimens that provide appropriate antibacterial coverage with the advantage of reduced dosing frequency, such as once daily ceftriaxone plus amikacin. Methods. Febrile neutropenic children with leukemia, lymphoma or solid tumors after chemotherapy were included in an open, prospective, randomized, multinational study comparing once daily ceftriaxone plus amikacin vs. 8-hourly ceftazidime and amikacin. The response to antimicrobial therapy was defined as complete response, improvement or failure. Assessment of adverse events was supplemented by specific definitions of nephrotoxicity, ototoxicity, hepatotoxicity and hypokalemia. Costs were estimated from published values of acquisition costs, delivery costs and hospitalization costs. Results. Efficacy was evaluable in 364 of 468 episodes in 265 children. Response rates in ceftriaxone and amikacin vs. ceftazidime and amikacin-treated episodes were 119 of 181 (66%) vs. 121 of 183 (66%), 7 of 181 (4%) vs. 9 of 183 (5%) and 55 of 181 (30%) vs. 53 of 181 (29%) for complete response, improvement and failure, respectively. Safety profiles were similar with both treatment regimens. The acquisition and administration costs were lower for the ceftriaxone and amikacin regimen. Conclusions. A once daily regimen of ceftriaxone and amikacin is as safe and clinically effective as that of three times daily ceftazidime and amikacin for the treatment of febrile neutropenic children with cancer and is more cost-effective. The once daily regimen of ceftriaxone and amikacin is suitable for outpatient treatment.