Chorioamnionitis is a major cause of maternal and neonatal morbidity. The term refers to inflammation of the amniotic fluid, membranes, placenta, and/or decidua and has been strongly associated with premature labor, occurring in 30% of babies born after premature labor with intact membranes and in 75% with premature rupture of membranes (PROM). 1 The incidence of chorioamnionitis varies considerably depending on the gestational age at the time of delivery, with rates as high as 41% in those born at less than 27 weeks' gestation, 15% between 28 to 36 weeks' gestation, and 2% at term gestation. 2 Most cases of chorioamnionitis are a consequence of intra-amniotic infection that has four main sources including ascending infection through the vagina, hematogenous spread through the placenta, retrograde seeding from AbstractChorioamnionitis contributes to neonatal and maternal morbidity and mortality. We aimed to evaluate of the impact of clinical and histological chorioamnionitis on mortality and morbidity of preterm infants. Maternal and neonatal data were collected in a retrospective cohort of preterm infants less than 30 weeks' gestation. Infants were divided into three groups: those born to mothers with clinical chorioamnionitis, histological chorioamnionitis, or no chorioamnionitis. Of 274 identified preterm infants, 33 infants were born to mothers with clinical chorioamnionitis, 95 to mothers with histological chorioamnionitis, and 146 to mothers with no chorioamnionitis. Data were available for 180 (78%) of the 230 survivors at 18 months corrected age. Infants in the study groups were similar in gestational age, birth weight, and sex distribution. Clinical and histological chorioamnionitis were not predictive of infant mortality, cerebral palsy, bronchopulmonary dysplasia, periventricular leukomalacia, or retinopathy of prematurity. Infants in the clinical chorioamnionitis group had significantly lower cognitive (88 AE 10), language (82 AE 12), and motor (89 AE 11) scores compared with infants in the histological chorioamnionitis group (101 AE 13, p < 0.01; 91 AE 13, p < 0.05; and 99 AE 13, p < 0.05, respectively) and to infants in the no chorioamnionitis group (99 AE 13, p < 0.01; 92 AE 15, p < 0.05; and 97 AE 13, p < 0.05, respectively). Clinical chorioamnionitis is associated with developmental delay in preterm infants despite adequate treatment.

f Variability in neonatal vancomycin pharmacokinetics and the lack of consensus for optimal trough concentrations in neonatal intensive care units pose challenges to dosing vancomycin in neonates. Our objective was to determine vancomycin pharmacokinetics in neonates and evaluate dosing regimens to identify whether practical initial recommendations that targeted trough concentrations most commonly used in neonatal intensive care units could be determined. Fifty neonates who received vancomycin with at least one set of steady-state levels were evaluated retrospectively. Mean pharmacokinetic values were determined using first-order pharmacokinetic equations, and Monte Carlo simulation was used to evaluate initial dosing recommendations for target trough concentrations of 15 to 20 mg/liter, 5 to 20 mg/liter, and <20 mg/liter. Monte Carlo simulation revealed that dosing by mg/kg of body weight was optimal where intermittent dosing of 9 to 12 mg/kg intravenously (i.v.) every 8 h (q8h) had the highest probability of attaining a target trough concentration of 15 to 20 mg/liter. However, continuous infusion with a loading dose of 10 mg/kg followed by 25 to 30 mg/kg per day infused over 24 h had the best overall probability of target attainment. Initial intermittent dosing of 9 to 15 mg/kg i.v. q12h was optimal for target trough concentrations of 5 to 20 mg/liter and <20 mg/ liter. In conclusion, we determined that the practical initial vancomycin dose of 10 mg/kg vancomycin i.v. q12h was optimal for vancomycin trough concentrations of either 5 to 20 mg/liter or <20 mg/liter and that the same initial dose q8h was optimal for target trough concentrations of 15 to 20 mg/liter. However, due to large interpatient vancomycin pharmacokinetic variability in neonates, monitoring of serum concentrations is recommended when trough concentrations between 15 and 20 mg/liter or 5 and 20 mg/liter are desired.

Background Although aminoglycosides are routinely used in neonates, controversy exists regarding empiric dosing regimens. The objectives were to determine gentamicin pharmacokinetics in neonates, and develop initial mg/kg dosing recommendations that optimized target peak and trough concentration attainment for conventional and extended-interval dosing (EID) regimens. Methods Patient demographics and steady-state gentamicin concentration data were retrospectively collected for 60 neonates with no renal impairment admitted to a level III neonatal intensive care unit. Mean pharmacokinetics were calculated and multiple linear regression was performed to determine significant covariates of clearance (L/h) and volume of distribution (L). Classification and regression tree (CART) analysis identified breakpoints for significant covariates. Monte Carlo Simulation (MCS) was used to determine optimal dosing recommendations for each CART-identified sub-group. Results Gentamicin clearance and volume of distribution were significantly associated with weight at gentamicin initiation. CART-identified breakpoints for weight at gentamicin initiation were: ≤ 850 g, 851-1200 g, and > 1200 g. MCS identified that a conventional dose of gentamicin 3.5 mg/kg given every 48 h or an EID of 8-9 mg/kg administered every 72 h in neonates weighing ≤ 850 g, and every 24 and 48 h, respectively, in neonates weighing 851-1200 g, provided the best probability of attaining conventional (peak: 5-10 mg/L and trough: ≤ 2 mg/L) and EID targets (peak:12-20 mg/L, trough:≤ 0.5 mg/L). Insufficient sample size in the > 1200 g neonatal group precluded further investigation of this weight category. Conclusions This study provides initial gentamicin dosing recommendations that optimize target attainment for conventional and EID regimens in neonates weighing ≤ 1200 g. Prospective validation and empiric dose optimization for neonates > 1200 g is needed.