Chorioamnionitis and elevated cord blood inflammatory cytokine concentrations are associated with detectable disturbances of systemic and cerebral hemodynamics in premature newborns. Fifty-five infants (25-31 wk gestation) were enrolled. Chorioamnionitis was defined by placental histology. IL-6, IL-1␤, and tumor necrosis factor-␣ were quantified by ELISA. Blood pressure, heart rate, cardiac output, stroke volume, fractional shortening, and middle cerebral artery blood flow velocities were measured at 3 Ϯ 1 h after birth. Chorioamnionitis was evident in 22 placentas and was associated with increased IL-6 (p Ͻ 0.001), IL-1␤ (p ϭ 0.035), and heart rate (p ϭ 0.027); and with decreased mean and diastolic blood pressure (p ϭ 0.026 and p ϭ 0.019, respectively). IL-6 concentration correlated inversely with systolic, mean, and diastolic blood pressures. Right ventricular cardiac output was elevated (p ϭ 0.028) in infants with fetal vessel inflammation. Maternal temperature Ն38.0°C and newborn immature-to-total white blood cell ratio Ն0.4 were associated with significant decreases in left ventricular fractional shortening (p ϭ 0.001 and p ϭ 0.005, respectively). Neither chorioamnionitis nor elevated cytokine concentrations were associated with changes in middle cerebral artery Doppler blood flow velocities. Chorioamnionitis and elevated cord blood IL-6 concentrations are associated with decreased blood pressure in premature newborns. Inflammation of the fetal vessels and nonspecific indicators of infection are associated with disturbances in cardiac function. Infants with chorioamnionitis and elevated cytokine concentrations do not manifest changes in cerebral Doppler indices within the first few postnatal hours. We speculate that cytokine-associated systemic hemodynamic disturbances in premature infants born after chorioamnionitis predispose such infants to perinatal brain injury. Hemodynamic abnormalities among premature infants are recognized to be important factors in the pathogenesis of perinatal brain injury. For example, IVH is more common in very low birth weight infants with hypotension (1) and fluctuating cerebral blood flow velocities (2). PVL may denote white matter ischemia (3) that results from compromised cerebral blood flow during a critical developmental period in which oligodendroglia undergo myelogenesis (4) in the presence of a tenuous vascular supply (5, 6). In fact, animals at a stage of brain development comparable to the Ͻ32-wk human fetus display a distinct and selective reduction of white matter blood flow in response to hypotension (7), confirming the predisposition for periventricular white matter ischemia at this gestational age.The ischemia theory of white matter injury has been challenged (8 -11) by the epidemiologic observation that chorioamnionitis is a strong predictor of subsequent PVL (12, 13) and cerebral palsy in both term (14) and preterm (13) infants. Although the mechanism of white matter injury in the context of infection has not been fully elucidated, evidence suggests that the p...

Background Suspected or complicated intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial agent with excellent activity against pathogens associated with intra-abdominal infections in this population. The purpose of this study was to determine the pharmacokinetics (PK) of meropenem in young infants as a basis for optimizing dosing and minimizing adverse events. Methods Premature and term infants <91 days of age hospitalized in 24 neonatal intensive care units were studied. Limited PK sampling was performed following single and multiple doses of meropenem 20–30 mg/kg of body weight every 8–12 hours based on postnatal and gestational age at birth. Population and individual patient (Bayesian) PK parameters were estimated using NONMEM®. Results Two hundred infants were enrolled and received study drug. One hundred eighty-eight infants with 780 plasma meropenem concentrations were analyzed. Their median (range) gestational age at birth and postnatal age at PK evaluation were 28 (23–40) weeks and 21 (1–92) days, respectively. In the final PK model, meropenem clearance (CL) was strongly associated with serum creatinine (SCR) and postmenstrual age (PMA) (CL [L/h/kg] = 0.12*[(0.5/SCR)**0.27]*[(PMA/32.7)**1.46]). Meropenem concentrations remained >4 μg/mL for 50% of the dose interval and >2 μg/mL for 75% of the dose interval in 96% and 92% of patients, respectively. The estimated penetration of meropenem into the cerebrospinal fluid was 70% (5–148). Conclusions Meropenem dosing strategies based on postnatal and gestational age achieved therapeutic drug exposure in almost all infants.

Tracheobronchomalacia is common in neonates with bronchopulmonary dysplasia who undergo bronchoscopy and is associated with longer and more complicated hospitalizations.

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Three once-a-week 90 or 60 mg/kg pagibaximab infusions, in high-risk neonates, seemed safe and well tolerated. No staphylococcal sepsis occurred in infants who received 90 mg/kg. Target levels were only consistently achieved after 2 to 3 doses. Dose optimization should enhance protection.

Drs Piazza, Pallotto, and Brozanski in collaboration provided leadership for the design and analytics of the collaborative; and drafted, reviewed, and revised the manuscript. Ms Zaniletti and Mr Provost provided data analytics and critically reviewed the manuscript. All authors participated in the design and management of the collaborative, approved the fi nal manuscript as submitted, and agreed to be accountable for all aspects of the work. DOI: 10.1542/peds.2014-3642Accepted for publication Sep 21, 2015 Address correspondence to Anthony J. Piazza, MD, Department of Pediatrics, Division of Neonatal Medicine, Emory School of Medicine, 2015 Uppergate Rd, Atlanta, GA 30322. E-mail: apiazza@ emory.edu PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).Health care-associated infections (HAIs) are a burden to patients and the health care system. It is estimated that up to 50% of HAIs are preventable. 1,2 In 2002, however, HAIs in US hospitals reportedly reached ∼1.7 million, with >33 000 HAIs among infants in high-risk nurseries. 3 Central line-associated bloodstream infections (CLABSIs) have the highest cost per HAI and contribute to significant morbidities, mortality, and length of stay in the adult, pediatric, and neonatal populations. [4][5][6] The overall direct annual cost of US HAIs ranges from $35.7 to $45 billion for inpatient hospital services. 7 Although the actual cost of CLABSIs varies, the attributable cost to care is up to $69 000 per event. [7][8][9][10][11] Despite the risks with their use, central venous catheters (CVCs) play an integral role in modern health care. 12 The need for CVCs is particularly important in children's hospital NICUs for patients who abstract OBJECTIVE: Reduce central line-associated bloodstream infection (CLABSI) rates 15% over 12 months in children's hospital NICUs. Use orchestrated testing as an approach to identify important CLABSI prevention practices. METHODS:Literature review, expert opinion, and benchmarking were used to develop clinical practice recommendations for central line care. Four existing CLABSI prevention strategies (tubing change technique, hub care monitoring, central venous catheter access limitation, and central venous catheter removal monitoring) were identified for study. We compared the change in CLABSI rates from baseline throughout the study period in 17 participating centers. Using orchestrated testing, centers were then placed into 1 of 8 test groups to identify which prevention practices had the greatest impact on CLABSI reduction. RESULTS:CLABSI rates decreased by 19.28% from 1.333 to 1.076 per 1000 line-days. Six of the 8 test groups and 14 of the 17 centers had decreased infection rates; 16 of the 17 centers achieved >75% compliance with process measures. Hub scrub compliance monitoring, when used in combination with sterile tubing change, decreased CLABSI rates by 1.25 per 1000 line-days. CONCLUSIONS:This multicenter improvement collaborative achieved a decrease in CLABSI rates. Orchestrated testing identified infection prev...

NCT00621192.