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Continuous-infusion vancomycin therapy in the neonatal population improves vancomycin serum concentrations

Presented at the Neonatal Society 2007 Summer Meeting (programme).

Kapetanakis A1, Bradley S2, Farrer K3 (introduced by Dr S Calvert)

1 Centre for Perinatal Brain Research, Institute for Women's Health, University College London, UK
2 Regional Neonatal Unit, St George’s Hospital NHS Trust, London, UK
3 Addenbrookes Hospital, Cambridge, UK

Background: Vancomycin is a valuable antibiotic in neonatal intensive care although the optimal administration regimen has not been established. Intermittent drug administration regimens do not produce consistently satisfactory drug levels. The most important pharmacokinetic parameter for vancomycin is the 24-hour area under the serum concentration time concentration curve (24 h AUC) in relation to minimal inhibitory concentration (MIC) (1,2). Continuous infusion (CI) vancomycin may therefore be more appropriate and improve serum drug concentrations and bactericidal activity. To date there is limited experience of CIvancomycin therapy in neonates (3).

Objective: To evaluate the use of a new CI-vancomycin therapy regimen in neonates

Design/Methods: Prospective data collection from infants receiving a loading dose 15 mg/kg followed by CI-vancomycin in accordance to UK ethical guidlines. The starting doses were 15mg/kg/day-30mg/kg/day depending on the initial serum creatinine level. Drug levels were obtained at 24-48 hour intervals and the dose adjusted accordingly.Target steady state concentration was 15-25mcg/ml.

Results: (mean ± Standard deviation): 119 vancomycin courses were evaluated between November 2002 and November 2006. Gestational age was 29.1 (±5.6) weeks and birth weight 1.23 (±0.88) kg. Corrected age at start of therapy 34.5 (±7.9) weeks. The dosing schedule was adjusted 2.1 (±2) times. Duration of the treatment was 12.5 (±5.8) days. 48 hour steady state vancomycin concentration: 16.75 (±8.2) mcg/ml (69% > 15 mcg/ml) and improved further during the treatment course. On day 2 of treatment 88.5% of the vancomycin concentrations measured between 10-25 mg/L 99.5% by day 5. No short-term complications were observed during the drug administration.

Conclusions: CI-vancomycin administration resulted in satisfactory drug concentrations in the neonatal population.Levels need to be monitored regularly and the dose adjusted accordingly to achieve optimal results. Further randomized study would be necessary to allow comparison with conventional intermittent vancomycin dosing regimens.

1. Moise-Broder PA, Forrest A, Birmingham MC, Schentag JJ. Clin Pharmacokinet 2004;43(13):925-42.
2. Rybak MJ.. Clin Infect Dis 2006;42 Suppl 1:S35-9.
3. Pawlotsky F, Thomas A, Kergueris MF, Debillon T, Roze JC.. Br J Clin Pharmacol 1998;46(2):163-7.

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