Pharmacokinetics and administration regimens of vancomycin in neonates, infants and children.

The increased use of vancomycin in neonatal and paediatric patients has prompted numerous pharmacokinetic studies and the development of many empirical administration methods. The majority of dosage guidelines use the relationship between pharmacokinetic parameters and patient variables such as chronological age, bodyweight, and/or measures of renal function. Currently, those dosage guidelines which are based upon postconceptional age and bodyweight seem to provide the best options for empirical administration in neonates and infants. In addition, serum creatinine may prove to be a useful guide to the empirical administration of vancomycin in neonates older than 7 to 14 days. Several investigators have reported the individualisation of dosage regimens based on pharmacokinetic-based administration methods. The most common techniques employed have been Sawchuk-Zaske method and Bayesian forecasting. However, only a limited number of studies have evaluated either empirical administration or individualised administration techniques in patient populations outside those of the original reports; this makes choosing between the methods difficult. Pharmacokinetic data and administration recommendations have gradually become available in special paediatric patient populations. The majority of studies have focused on patients requiring cardiopulmonary bypass surgery or with burns, cancer or central nervous system infections. However, a limited amount of information is available regarding vancomycin disposition in children older than 1 year of age with and without end-stage renal failure. The monitoring of serum vancomycin concentrations may be useful in selected neonatal and paediatric patient populations, especially where large interpatient variability occurs and administration guidelines are not clearly established. Similar to the literature on adults, the lack of conclusive evidence concerning the relationship between serum vancomycin concentrations and therapeutic responses leaves this topic open to debate.

Allograft tolerance by intrathymic donor splenocyte transfer: an age-dependent, species-specific phenomenon?

Protocols that allow allograft survival without immunosuppression remain the ultimate goal in transplantation. Intrathymic injection of donor splenocytes into a transiently immunosuppressed recipient has induced tolerance to a variety of subsequently transplanted allografts in rats. The purpose of this study was to determine if recipient age is critical to intrathymic tolerance in light of age-dependent thymic changes, and if this protocol can be extended to an outbred, large animal model. Prepubertal and postpubertal Wistar-Furth rats underwent intrathymic injection of splenocytes from Lewis rats and antilymphocyte serum (ALS) intraperitoneally. On day 21, a heterotopic Lewis heart was transplanted, with graft survival evaluated by cardiac palpation. Graft tolerance (> 100 days) occurred in four out of five (80%) of the prepubertal rats compared to two out of six (33%) postpubertal rats. Tolerance was not demonstrated in rats receiving intrathymic injection of buffer only. In puppies, groups 1 and 2 underwent splenectomy with intrathymic injection of allo splenocytes. Control puppies (group 3) received intrathymic auto splenocytes. Groups 1 and 3 were given antilymphocyte gamma globulin (ALG) on days 7 to 0 with respect to the intrathymic injection. Group 2 did not receive ALG, but instead received cyclosporin A (CSA) on days 0-2. On day 21, all puppies underwent bilateral nephrectomy and single renal transplantation. No additional immunosuppression was given. Tolerance (creatinine < 7 mg/dl for 100 days) was not obtained by any dog in all three groups. There was no difference in graft survival between control and experimental dogs, with the longest surviving graft seen in a control dog (26 days). Our results suggest that thymic change during maturation may alter the ability to induce tolerance by intrathymic injection of donor cells in rats, and that the protocol is not easily adapted to large animals.