Journal of Antimicrobial Chemotherapy (2001) 48, 887-893
© 2001 The British Society for Antimicrobial Chemotherapy
An extended interval dosing method for gentamicin in neonates
a Department of Paediatrics, Neonatal Intensive Care Unit, Christchurch Womens Hospital, Christchurch; b Department of Clinical Pharmacology, Christchurch Hospital, PO Box 4710, Christchurch, New Zealand; c School of Pharmacy, University of Queensland, Australia
Traditional gentamicin dosing every 8–24 h depending on age and weight in neonates does not provide the ideal concentration–time profile to both optimize the concentration-dependent killing by aminoglycosides and minimize toxicity. Fifty-three neonates were audited prospectively while receiving gentamicin 2.5 mg/kg every 8–24 h, aiming for peak concentrations (Cmax) of 6–10 mg/L and trough concentrations (Cmin) <2 mg/L. After the first dose, the mean (± s.d.) Cmax was 5.5 ± 0.7 mg/L with sub-therapeutic concentrations (<6 mg/L) in 62% of patients, while the mean Cmin was >2 mg/L in 15% of the neonates. After the third dose the Cmax was 7.5 ± 1.5 mg/L, with 17% <6 mg/L, whereas the mean Cmin was 2.2 ± 1.1 mg/L with 49% of values >2 mg/L. An extended interval dosing method (24, 36 and 48 h) for infant weights of 0.75–5 kg was developed by simulation, and audited prospectively in 51 neonates. Prospective analysis of the extended interval dosing method showed a mean Cmax after the first dose of 13.1 ± 3.6 mg/L, while the mean Cmin was 0.7 ± 0.6 mg/L. Seventy-eight per cent had Cmax of >10 mg/L after the first dose. The mean area under the concentration versus time curve AUC0–24 was 93 mg•h/L (target = 100 mg•h/L). The extended interval dosing achieved higher Cmax values while ensuring that overall exposure per 24 h was acceptable. Prospective testing of the method demonstrated good predictive ability.
* Corresponding author. Tel: +643-364-1055; Fax: +643-364-0902; E-mail: carl.kirkpatrick{at}cdhb.govt.nz
Dr Mark Stickland died in an accident during the final stages of this project and was thus unable to approve the final version of the manuscript. A decision was made in discussion between the other authors and the Editorial staff that Dr Stickland would remain as senior author, in view of the tragic and highly unusual circumstances.
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