Pharmacokinetics of Vancomycin in Pediatric Patients Receiving Intermittent Hemodialysis or Hemodiafiltration.

INTRODUCTION: Vancomycin is a common antibiotic used to treat hemodialysis (HD) or hemodiafiltration (HDF)-related infections in pediatric patients, but optimal dosing remains unknown. This is the first observational study to characterize the pharmacokinetics and evaluate dosing of vancomycin in this population. METHODS: Eligible patients received IV vancomycin 10 mg/kg per dose postdialysis followed by a series of serum vancomycin concentrations collected before, immediately after, 1 hour after, and 4 hours after dialysis. The pharmacokinetic parameters were estimated using 1- and 2-compartment models and a nonlinear least-squares algorithm. RESULTS: Among 42 vancomycin courses in 16 patients, 1 compartment model had the best fit for observed data. The net drug removal was 43 ± 13% (39% for HD and 50% for HDF) from an average 3-hour HD/HDF session. The mean elimination constant was 0.28 h-1 (standard deviation [SD], 0.11 h-1) during the intradialytic period compared with 0.0049 h-1 (SD, 0.004 h-1) when off dialysis. The mean volume of distribution was 0.65 (SD, 0.19) L/kg. Duration of dialysis session and mode of dialysis (HD vs. HDF) were significant predictors of vancomycin pharmacokinetic parameters. Half-life was shorter for HDF compared with HD (2.1 vs. 3.5 hours). CONCLUSIONS: Based on the simulations, an initial vancomycin dose of 10 mg/kg per dose and redosing postdialysis was optimal to achieve a vancomycin concentration range of 5 to 12 mg/L at 4 hours postdialysis and 24-hour area under the curve over minimum inhibitory concentration of ≥400 hours. Therapeutic drug monitoring is necessary to account for residual variability in vancomycin elimination in pediatric patients receiving HD/HDF.

Efficacy and safety of proton pump inhibitors in the management of pediatric gastroesophageal reflux disease.

Proton pump inhibitors (PPIs) are commonly prescribed to infants and children for managing gastroesophageal reflux disease (GERD). Recently published literature illustrates conflicting evidence on the efficacy of PPIs in infants and children. Randomized controlled trials and systematic reviews have demonstrated a lack of efficacy of PPIs, specifically in young infants. Furthermore, emerging evidence also suggests that PPIs are not as benign as once thought, with newer data implicating a potential association of PPIs with an increased risk of respiratory tract infections, gastrointestinal infections, bone fractures, hypomagnesemia, and the occurrence of rebound hyperacidity after discontinuation of PPI therapy. To summarize the emerging data in children, we reviewed the literature to assess the efficacy and safety of PPIs in managing pediatric GERD. Despite conflicting evidence on the efficacy of PPIs, most studies in children demonstrated some benefit when compared with placebo. With respect to the safety of PPIs in children, only a few small studies and case reports indicated a potential association of PPIs with an increased risk of respiratory tract or gastrointestinal infections, bone fractures, and hypomagnesemia; however, many of those studies had their own limitations. From the review, it is clear that further well-designed trials and observational studies are needed to shed more light on the efficacy and safety of PPIs in the pediatric population.