CHANGES IN VANCOMYCIN PHARMACOKINETICS IN CRITICALLY ILL INFANTS

We aimed to assess the pharmacokinetics of vancomycin in critically il l infants, and to evaluate the standard recommended dose of 70 mg/kg 6 hourly. All infants admitted to the Baragwanath Hospital ICU who had arterial lines in situ, and for whom vancomycin 10 mg/kg 6 hourly was prescribed for an infective insult and who had parental consent, were included in the study. Vancomycin was infused over 60 minutes. Serum s amples were taken immediately before the dose and at 30, 60, 120 and 3 00 minutes after the end of the vancomycin infusion, on days 2 and 8 o f therapy. Extrapolated peak concentration (Cmax), trough concentratio n (Cmin), apparent volume of distribution (Vd) elimination half-life ( t(1/2el)) and clearance (CL) were determined for each patient. Day 2 v alues were compared with those of day 8. Day 2 serum concentrations we re assayed on 20 patients and day 8 concentrations in 15. The mean van comycin Vd on day 2 (0.81 l/kg) was significantly (P=0.007) larger tha n that on day 8 (0.44 l/kg). The change in Vd resulted in a significan t change in mean Cmax (29.1 vs 35.5 mu g/ml) (P=0.02) and mean t(1/2el ) (5.3 vs 3.4h) (P=0.01) over the treatment period. Critically ill inf ants displayed a large initial volume of distribution which probably r esulted from aggressive fluid resuscitation. This also results in a la rge variation in other pharmacokinetic parameters, namely Cmax and t(1 /2el). Although the routine monitoring of vancomycin serum concentrati ons remain controversial, we feel that in view of these large pharmaco kinetic variations, the critically ill infant is a specific group wher e monitoring of vancomycin serum levels is indicated.