Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

There are very few human MAIT cells in cord blood. Ben Youssef et al. show that they slowly expand during childhood and point to a critical role of the TCRαβ repertoire in determining their unique ability to recognize MR1-restricted microbial antigens.

N eonatal bacterial sepsis, exacerbated by neonatal immunodeficiency (1), remains a major cause of mortality and morbidity in newborns (2). Vancomycin is widely used for the treatment of late-onset sepsis caused by methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci in neonatal intensive care units (NICUs) (3); however, the clinical use of vancomycin is still hampered by its narrow therapeutic index and high pharmacokinetic variability (4). Indeed, de Hoog et al. reported that vancomycin clearance and half-life varied between 0.63 and 1.4 ml/ kg/min and between 3.5 and 10 h in neonates, respectively (4). The common adverse effects of vancomycin are nephrotoxicity and ototoxicity; however, it has been shown that neonates tolerated vancomycin better than adults. Safety data for a high dosing regimen and long-term follow-up are still lacking.The pharmacokinetic modeling approach is often applied to evaluate and optimize antimicrobial therapy in neonates (5). To date, vancomycin is one of the best-studied antimicrobials, and numerous studies have been conducted to characterize its pharmacokinetic parameters and to identify individual factors influencing variability (6). However, the clinical application of modelbased personalized vancomycin therapy is still limited. The objective of the present study was to evaluate the clinical utility and safety of a patient-tailored dose of vancomycin in neonates. Model-based patient-tailored dose of vancomycin. Special training was conducted in each NICU. We first informed the staff of the clinical pharmacology of vancomycin, its pharmacokinetic variability, and a large variation of dosage schedules currently used. We then explained the principles of individual dosage adaptation and how we developed the Excel dosing calculator using the results from our published population pharmacokinetic model (6). MATERIALS AND METHODS Neonates receiving vancomycin as a continuous infusion in one of threeIn order to calculate the patient-tailored dosing of vancomycin for each neonate, neonatologists had to enter four patient covariates in the calculator, including birth weight (in grams), current weight (in grams), postnatal age (PNA; in days), and serum creatinine concentration (in micromoles per liter) measured within 48 h of starting vancomycin treatment. The developed calculator was locked, and no other information was required. The patient-tailored dose is calculated automatically by using the following pharmacokinetic equations.Maintenance dose ϭ Target concentration ϫ CL ϫ 24 hwhere the loading dose is in milligrams, the maintenance dose is in milligrams per 24 h, the target concentration is in milligrams per liter, V (vol-

The prevention of perinatal brain damage following preterm birth remains a public health priority. Melatonin has been shown to be a promising neuroprotectant in neonatal preclinical models of brain damage, but few studies have investigated melatonin secretion in newborns. We hypothesized that melatonin circulating levels would be lower in preterm compared to term infants. We conducted a prospective, longitudinal, multicenter study to assess melatonin, and 6-sulfatoxy-melatonin (aMT6s) concentrations, measured by radioimmunoassay. Among 209 neonates recruited, 110 were born before 34 gestational weeks (GW) and 99 born after 34 GW. Plasma melatonin concentrations, measured at birth and on Day 3 were below detectable levels (≤7 pg/mL) in 78% and 81%, respectively, of infants born before 34 GW compared to 57% and 34%, respectively, of infants born after 34 GW. The distribution of plasma melatonin concentrations was found to be correlated with gestational age at both time-points (p < 0.001). Median urine aMT6s concentrations were significantly lower in infants born before 34 GW, both on Day 1 (230 ng/L vs. 533 ng/L, p < 0.0001) and on Day 3 (197 ng/L vs. 359 ng/L, p < 0.0001). In conclusion, melatonin secretion appears very low in preterm infants, providing the rationale for testing supplemental melatonin as a neuroprotectant in clinical trials.