Ceftazidime is an antibiotic commonly used to treat bacterial infections in term neonates undergoing controlled therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy after perinatal... Show moreCeftazidime is an antibiotic commonly used to treat bacterial infections in term neonates undergoing controlled therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy after perinatal asphyxia. We aimed to describe the population pharmacokinetics (PK) of ceftazidime in asphyxiated neonates during hypothermia, rewarming, and normothermia and propose a population-based rational dosing regimen with optimal PK/pharmacodynamic (PD) target attainment. Data were collected in the PharmaCool prospective observational multicenter study. A population PK model was constructed, and the probability of target attainment (PTA) was assessed during all phases of controlled TH using targets of 100% of the time that the concentration in the blood exceeds the MIC (T->MIC) (for efficacy purposes and 100% T->4xMIC and 100% T->5xMIC to prevent resistance). A total of 35 patients with 338 ceftazidime concentrations were included. An allometrically scaled one-compartment model with postnatal age and body temperature as covariates on clearance was constructed. For a typical patient receiving the current dose of 100 mg/kg of body weight/day in 2 doses and assuming a worst-case MIC of 8 mg/L for Pseudomonas aeruginosa, the PTA was 99.7% for 100% T->MIC during hypothermia (33.7 degrees C; postnatal age [PNA] of 2 days). The PTA decreased to 87.7% for 100% T->MIC during normothermia (36.7 degrees C; PNA of 5 days). Therefore, a dosing regimen of 100 mg/kg/day in 2 doses during hypothermia and rewarming and 150 mg/kg/day in 3 doses during the following normothermic phase is advised. Higher-dosing regimens (150 mg/kg/day in 3 doses during hypothermia and 200 mg/kg/day in 4 doses during normothermia) could be considered when achievements of 100% T->4xMIC and 100% T->5xMIC are desired. Show less
Halbmeijer, N.M.; Onland, W.; Cools, F.; Kroon, A.; Heide-jalving, M. van der; Dijk, P.; ... ; SToP-BPD Study Grp 2022
Objective Observational studies in preterm infants suggest that systemic hydrocortisone improves pulmonary condition but may also lead to systemic adverse effects. We report the short-term... Show moreObjective Observational studies in preterm infants suggest that systemic hydrocortisone improves pulmonary condition but may also lead to systemic adverse effects. We report the short-term pulmonary and systemic effects of hydrocortisone initiated in the second week.Design Randomised placebo-controlled trial.Setting Dutch and Belgian neonatal intensive care units.Patients Infants born <30 weeks' gestation and/or birth weight <1250 g, and ventilator dependent in the second week of life.Intervention Infants were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190).Main outcome measures Data on extubation, ventilator settings, glucose levels, and blood pressure were recorded daily and analysed during the first 7 days of treatment using linear mixed-effects models.Results Infants in the hydrocortisone group (24.3%) failed extubation less often compared with placebo (38.6%, crude risk difference: -14.3% (95% CI: -23.4% to -4.8%)). The estimated difference in daily rate of change between hydrocortisone and placebo was -0.42 cmH(2)O (95% CI: -0.48 to -0.36) for mean airway pressure, -0.02 (95% CI: -0.02 to -0.01) for fraction of inspired oxygen, -0.37 (95% CI: -0.44 to -0.30) for respiratory index, 0.14 mmol/L (95% CI: 0.08 to 0.21) for blood glucose levels and 0.83 mm Hg (95% CI: 0.58 to 1.09) for mean blood pressure.Conclusions Systemic hydrocortisone initiated between 7 and 14 days after birth in ventilated preterm infants improves pulmonary condition, thereby facilitating weaning and extubation from invasive ventilation. The effects of hydrocortisone on blood glucose levels and blood pressure were mild and of limited clinical relevance. Show less
Baas, E.M.; Romijn, M.; Pal, S.M. van der; Vrijlandt, E.J.L.E.; Rotteveel, J.; Finken, M.J.J.; ... ; Dutch POPS 19 Col 2021
Objective To compare the effect of intervention at low vs high threshold of ventriculomegaly in preterm infants with posthemorrhagic ventricular dilatation on death or severe neurodevelopmental... Show moreObjective To compare the effect of intervention at low vs high threshold of ventriculomegaly in preterm infants with posthemorrhagic ventricular dilatation on death or severe neurodevelopmental disability.Study design This multicenter randomized controlled trial reviewed lumbar punctures initiated after either a low threshold (ventricular index of >p97 and anterior horn width of >6 mm) or high threshold (ventricular index of >p97 + 4 mm and anterior horn width of >10 mm). The composite adverse outcome was defined as death or cerebral palsy or Bayley composite cognitive/motor scores <-2 SDs at 24 months corrected age.Results Outcomes were assessed in 113 of 126 infants. The composite adverse outcome was seen in 20 of 58 infants (35%) in the low threshold group and 28 of 55 (51 %) in the high threshold (P = .07). The low threshold intervention was associated with a decreased risk of an adverse outcome after correcting for gestational age, severity of intraventricular hemorrhage, and cerebellar hemorrhage (aOR, 0.24; 95% CI, 0.07-0.87; P = .03). Infants with a favorable outcome had a smaller fronto-occipital horn ratio (crude mean difference, -0.06; 95% CI, -0.09 to -0.03; P < .001) at term-equivalent age. Infants in the low threshold group with a ventriculoperitoneal shunt, had cognitive and motor scores similar to those without (P = .3 for both), whereas in the high threshold group those with a ventriculoperitoneal shunt had significantly lower scores than those without a ventriculoperitoneal shunt (P = .01 and P = .004, respectively).Conclusions In a post hoc analysis, earlier intervention was associated with a lower odds of death or severe neurodevelopmental disability in preterm infants with progressive posthemorrhagic ventricular dilatation. Show less
