Optimization of ß-Lactam Dosing Regimens in Neonatal Infections: Continuous and Extended Administration versus Intermittent Administration.

BACKGROUND AND OBJECTIVE: In neonates, ß-Lactam antibiotics are almost exclusively administered by intermittent infusion. However, continuous or prolonged infusion may be more beneficial because of the time-dependent antibacterial activity. In this pharmacokinetic/pharmacodynamic simulation study, we aimed to compare treatment with continuous, extended and intermittent infusion of ß-lactam antibiotics for neonates with infectious diseases. METHODS: We selected population pharmacokinetic models of penicillin G, amoxicillin, flucloxacillin, cefotaxime, ceftazidime and meropenem, and performed a Monte Carlo simulation with 30,000 neonates. Four different dosing regimens were simulated: intermittent infusion in 30 min, prolonged infusion in 4 h, continuous infusion, and continuous infusion with a loading dose. The primary endpoint was 90% probability of target attainment (PTA) for 100% ƒT>MIC during the first 48 h of treatment. RESULTS: For all antibiotics except cefotaxime, continuous infusion with a loading dose resulted in a higher PTA compared with other dosing regimens. Sufficient exposure (PTA >90%) using continuous infusion with a loading dose was reached for amoxicillin (90.3%), penicillin G (PTA 98.4%), flucloxacillin (PTA 94.3%), cefotaxime (PTA 100%), and ceftazidime (PTA 100%). Independent of dosing regimen, higher meropenem (PTA for continuous infusion with a loading dose of 85.5%) doses might be needed to treat severe infections in neonates. Ceftazidime and cefotaxime dose might be unnecessarily high, as even with dose reductions, a PTA > 90% was retained. CONCLUSIONS: Continuous infusion after a loading dose leads to a higher PTA compared with continuous, intermittent or prolonged infusion, and therefore has the potential to improve treatment with ß-lactam antibiotics in neonates.

The effect of individualized iron supplementation on iron status in Dutch preterm infants born between 32 and 35 weeks of gestational age: evaluation of a local guideline.

OBJECTIVE: Iron deficiency (ID) and iron deficiency anemia (IDA) in early life are associated with adverse effects. Preterm infants are at risk for developing ID(A). Considering that not every preterm infant develops ID(A) and the potential risk of iron overload, indiscriminate iron supplementation in late preterm infants is debatable. This study aimed to evaluate the effect of a locally implemented guideline regarding individualized iron supplementation on the prevalence of ID(A) at the postnatal age of 4-6 months in Dutch preterm infants born between 32 and 35 weeks of gestational age (GA). METHODS: An observational study comparing the prevalence of ID(A) at the postnatal age of 4-6 months in Dutch preterm infants born between 32 and 35 weeks of GA before (i.e. PRE-guideline group) and after (i.e. POST-guideline group) implementation of the local guideline. RESULTS: Out of 372 eligible preterm infants, 110 were included (i.e. 72 and 38 in the PRE- and POST-guideline group, respectively). ID- and IDA-prevalence rates at 4-6 months of age in the PRE-guideline group were 36.1% and 13.9%, respectively, and in the POST-guideline group, 21.1% and 7.9%, respectively, resulting in a significant decrease in ID-prevalence of 15% and IDA-prevalence of 6%. No indication of iron overload was found. CONCLUSION: An individualized iron supplementation guideline for preterm infants born between 32 and 35 weeks GA reduces ID(A) at the postnatal age of 4-6 months without indication of iron overload.

[A newborn with an abnormal position of both legs]. / Een pasgeborene met een afwijkende stand van de benen.

A baby was born with an abnormal position of both legs due to congenital genu recurvatum. This is a rare condition which can appear as an isolated deformity, but is also associated with other musculoskeletal anomalies and syndromes. The prognosis is generally good.

[A neonate with dark brown coloured buttocks and upper legs]. / Een neonaat met donkerbruine billen en bovenbenen.

A neonate was seen by the pediatrician because of a well-defined macular hyperpigmentation of the skin in the genital area. The diagnosis 'giant congenital melanocytic nevi (CMN)' was made. This occurs in 1 of 20.000 newborns. Children with giant CMN may develop neurocutaneaous melanosis of the central nervous system. They have an increased life time risk of 5% of developing melanoma.