Once-daily netilmicin for neutropenic pyrexia in paediatric oncology

To establish the safety and efficacy of single daily intravenous netilmicin 6 mg/kg with piperacillin 100 mg/kg every 8 h for empirical, first-line management of children with neutropenic pyrexia following cytotoxic chemotherapy.

Observational study of children admitted to a regional oncology unit from October 1999-April 2002. Primary outcome measure was temperature 72 h after commencing antibiotic therapy; secondary measures were mortality, nephrotoxicity, symptomatic ototoxicity and serum netilmicin levels.

280 episodes for 128 patients (median age 7.1 y) were documented, and 248 episodes were evaluated and compared with a previous cohort of 100 episodes for which the only difference was administration of netilmicin three times daily. Twenty-seven per cent of single-dose netilmicin episodes remained febrile at 72 h compared to 32% in the comparator group (difference -4.7%; 95 % CI: -6.8% to 16.2%; p = 0.41). No patients died and we were unable to find evidence of nephrotoxicity or ototoxicity. Eighty-nine per cent of "peak" serum netilmicin levels measured 30 min after infusion were 10 mg/l or greater, and 94% and 86% measured 12-16 h after the first and third dose, respectively, were 1 mg/l or less. Peak serum netilmicin level measurements and 12-16-h measurements after the first dose were abandoned after the first 180 episodes.

Netilmicin can safely be given as a single daily dose to children with febrile neutropenia who do not have biochemical evidence of nephrotoxicity. Monitoring peak serum levels of netilmicin is unnecessary. Levels taken 12-16 h after the third dose are adequate to monitor therapy if used in conjunction with a therapeutic guideline detailing the response to abnormal serum creatinine and netilmicin levels.