BackgroundRotavirus is the leading cause of acute gastroenteritis in children and is associated with neurological complications such as seizures and encephalopathy. The aim of this study was to investigate the presentation and complications of rotavirus compared to non-rotavirus gastroenteritis in UK children.MethodsThis was a retrospective, case-control, hospital-based study conducted at three sites in east London, UK. Cases were children aged 1 month to 16 years diagnosed with acute gastroenteritis between 1 June 2011 and 31 December 2013, in whom stool virology investigations confirmed presence of rotavirus by PCR. They were matched by age, gender and month of presentation to controls with rotavirus-negative gastroenteritis.ResultsData were collected from 116 children (50 cases and 66 controls). Children with rotavirus gastroenteritis tended to present more frequently with metabolic acidosis (pH 7.30 vs 7.37, P = 0.011) and fever (74% versus 46%; P = 0.005) and were more likely to require hospitalisation compared to children with non-rotavirus gastroenteritis (93% versus 73%; P = 0.019). Neurological complications were the most common extra-intestinal manifestations, but did not differ significantly between children with rotavirus-positive gastroenteritis (RPG) and rotavirus-negative gastroenteritis (RNG) (24% versus 15%, respectively; P = 0.24). Encephalopathy occurred only in children with rotavirus infection (n = 3, 6%).ConclusionRotavirus causes longer and more severe disease compared to other viral pathogens. Seizures and milder neurological signs were surprisingly common and associated with multiple pathogens, but encephalopathy occurred only in children with rotavirus gastroenteritis. Rotavirus vaccination may reduce seizures and presentation to hospital, but vaccines against other pathogens causing gastroenteritis are required.

Background:Vancomycin is commonly used for nosocomial bacterial pathogens causing late-onset septicemia in preterm infants. We prospectively collected pharmacokinetic data aiming to describe PK and determine covariates contributing to the variability in neonatal vancomycin pharmacokinetics. Further, we aimed to use the model to compare AUC24h,SS/MIC of several intermittent and continuous dosing regimens. Methods: Newborns receiving vancomycin for suspected or confirmed late-onset sepsis were included. Peak and trough concentrations for intermittent vancomycin dosing and steady-state concentrations for continuous vancomycin dosing were measured. NONMEM 7.3 was used for population pharmacokinetic analysis. Monte Carlo simulations were performed to compare dosing schemes. Results: Data from 54 infants were used for model development and from 34 infants for the model evaluation of a median (range) 29 (23.4-41.9) weeks and 28 (23.4-41.7) weeks corrected gestational age (GA), respectively. The final model was a 1-compartment model. Weight and postmenstrual age were included a priori; and after that no additional covariate significantly improved the model fit. Final model parameter estimates (mean (standard error)): CL 5.7 (0.3) L/h/70kg, V 39.3 (3.7) L/70kg. Visual predictive check of the evaluation dataset confirmed the model can predict external data. Simulations using MIC of 1 mg/Lshowed that for neonates with GA ≤25 weeks and postnatal age ≤2 weeks AUC24h,SS/MIC was lower with the intermittent regimen (median 482 versus 663). Conclusions:A population PK model for continuous and intermittent vancomycin administration in infants was developed. Continuous administration might be favourable for treating infections caused by resistant microorganisms in very young and immature infants.

We conclude that amsalog can be safely given on a 5-day schedule every 3 weeks at doses up to 200 mg/m2. The dose recommended for further studies is 180 mg/m2 per day for 5 days repeated every 3 weeks. However, in view of the phlebitis, which necessitated the use of central venous catheters for administration, other routes of administration, for example oral formulations, should be explored.