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Re: Giving vancomycin as a continuous infusion

The recent paper advocating “a new dosage schedule” for giving vancomycin in early infancy [1] confirms what others have long said is usually the most appropriate total daily dose for babies of less than 34 weeks gestation who are more than a week old, and focuses on the time- dependent rather than concentration-dependent mode of vancomycin killing. Continuous infusion may prevent the risks of high peaks and low troughs seen with intermittent dosage. However, we disagree with the suggestion that a first loading dose is not necessary. The earlier paper that recommended this same strategy ten years ago [2] correctly said

“Vancomycin half-life is usually between 3 and 10 hr in neonates. The time to reach steady state, which is 4 to 5 times the half-life, might thus be expected to be around 48 hours in this specific population. Such a time to reach early bactericidal efficacy appeared too long in cases of septicaemia. For this reason, we decided to inject a 7 mg.kg -1 loading dose.”

The one trial to look at the relative merits of intermittent and continuous infusion, which found no evidence that continuous infusions were better than intermittent infusions in adults [3] also used a loading dose. The reference used to justify the assertion that a loading dose is not necessary was data presented by poster stating that therapeutic levels were reached within 12 hours in much older children, [4] but this overlooks the fact that the half life is much shorter in 5-10 year old children than it is in the first few weeks of life and, indeed, also rather shorter than it is adult life.

Failure to give a loading dose where there is clear evidence of septicaemia will leave any young baby dangerously under-treated for many hours. There are reasons for thinking that a continuous infusion may be a useful option when treating meningitis, as the discussion of these issues in the Neonatal Formulary web site argues [5], but a loading dose is required.

Dr Nicholas D Embleton (n.d.embleton@ncl.ac.uk), Dr Janet Berrington

Newcastle Neonatal Service, Royal Victoria Infirmary, Newcastle Hospitals NHS Trust, Newcastle upon Tyne NE1 4LP

References 1. Plan O, Cambonie G, Barbotte E, et al. Continuous-infusion vancomycin therapy for preterm neonates with suspected or documented Gram-positive infections: a new dosage schedule. Arch Dis Child 2008;93:F418–21.

2. Pawlotsky F, Thomas A, Kergueris MF, et al. Constant rate infusion of vancomycin in premature neonates: a new dosage schedule. Br J Clin Pharmacol 1998;46:163–7.

3. Wysocki M, Delatour F, Faurisson F, et al. Continuous versus intermittent infusion of vancomycin in severe staphylococcal infections: prospective multicenter randomised trial. Antimicrob Agents Chemother 2001;45:2460–7. 4. Le Normand Y, Avetloiseau H, Kergueris F, et al. Ceftazidime and vancomycin constant-rate infusion in neutropenic children: pharmacokinetic parameters and clinical implications. [Abstract] Antimicrob Agents Chemother 1993;37;A939

5. Vancomycin. [www.neonatalformulary.com]