Vancomycin pharmacokinetics in infants: relationship to postconceptional age and serum creatinine.

Multidose pharmacokinetics of vancomycin were studied in 15 infants with gestational age less than 36 weeks and suspected or confirmed Staphylococcus epidermidis infections. Postconceptional age (PCA) at the time of the study ranged from 26 to 44 weeks. Vancomycin individual doses ranged from 6.7 to 10.6 mg/kg and were infused over 60 min. Five postinfusion samples were obtained in 13 infants, while 4 samples were obtained in 2 patients. Vancomycin pharmacokinetic parameters were determined by fitting the data to a two-compartment model using a weighted least-squares nonlinear regression method. Mean vancomycin body clearance (CL), volume of distribution (Vdss) and terminal elimination half-life were 1.37 ml/min, 0.58 liters and 5.6 h, respectively. When standardized for patient weight, the CL and Vdss values were 1.07 ml/min/kg and 0.48 liters/kg, respectively. The CL (ml/min/kg) was strongly inversely correlated with the serum creatinine (r = -0.82), while a weaker but significant association was noted with PCA (r = 0.41). These data suggest that in sick infants, in addition to the PCA, serum creatinine should be considered when determining the initial vancomycin dosing regimen.

Direct determination of tobramycin clearance in patients with mild-to-moderate cystic fibrosis.

Studies performed in patients with cystic fibrosis (CF) have suggested altered pharmacokinetic parameters for aminoglycosides. Specifically, increased plasma clearance (Cl) of aminoglycosides and increased apparent volume of distribution have been noted. In the present study, tobramycin Cl is determined by both serum concentration data and direct renal clearance (Clren). Tobramycin Clren appeared to be directly correlated to the measured creatinine clearance (Clcr) (r = 0.93, p less than 0.01). The tobramycin Cl, by both methods of determination, was not elevated in comparison to the Clcr or expected values for patients without the disease. These results appear to corroborate a recent study in which the renal and plasma Cl of gentamicin was measured in patients with mild-to-moderate CF and were not noted to be elevated. It is suggested that standard doses of tobramycin be used initially in patients with mild-to-moderate CF with dosage adjustment based on serum concentration data to achieve the desired goals.

Medication error prevention by clinical pharmacists in two children's hospitals.

The purpose of this study was to record prospectively the frequency of and potential harm caused by errant medication orders at two large pediatric hospitals. The objective of the study was to assess the impact of pharmacist intervention in preventing potential harm. The study was conducted during a 6-month period. A total of 281 and 198 errors were detected at the institutions. The overall error rates for the two hospitals were 1.35 and 1.77 per 100-patient days, and 4.9 and 4.5 per 1,000 medication orders, respectively. Pediatric patients aged 2 years and less and pediatric intensive care unit patients received the greatest proportion of errant orders. Neonatal patients received the lowest rate of errant orders. The most common type of error was incorrect dosage, and the most prevalent type of error was overdosage. Antibiotics was the class of drugs for which errant orders were most common. Orders for theophylline, analgesics, and fluid and electrolytes, including hyperalimentation, were also frequently in error. In general, the error rate was greatest among physicians with the least training, but no physician group was error free. Involving pharmacists in reviewing drug orders significantly reduced the potential harm resulting from errant medication orders.