Antimicrobial Agent Dosing in Infants

AbstractPurposeThe goal of this article was to review infant physiology and its effects on the pharmacokinetic properties of antimicrobial agents.MethodsA review of the drug development process was performed. A literature search was conducted on the pharmacokinetics of various antimicrobial agents in infants.FindingsThe pharmacokinetic properties of antimicrobial agents in infants are most often affected by the renal maturation of premature infants. Hepatic metabolism and volume of distribution play a common role as well.ImplicationsThe dosing and dosing intervals of various medications were reviewed and compared with details of adult dosing. It is vital to continue to gather pharmacokinetic data in infants to ensure adequate safety and dosing of medications

Periodic Coupled-Cluster Green's Function for Photoemission Spectra of Realistic Solids

We present an efficient implementation of coupled-cluster Green's function (CCGF) method for simulating photoemission spectra of periodic systems. We formulate the periodic CCGF approach with Brillouin zone sampling in Gaussian basis at the coupled-cluster singles and doubles (CCSD) level. To enable CCGF calculations of realistic solids, we propose an active-space self-energy correction scheme by combining CCGF with cheaper many-body perturbation theory (GW) and implement the model order reduction (MOR) frequency interpolation technique. We find that the active-space self-energy correction and MOR techniques significantly reduce the computational cost of CCGF while maintaining the high accuracy. We apply the developed CCGF approaches to compute spectral properties and band structure of silicon (Si) and zinc oxide (ZnO) crystals using triple-$\zeta$ Gaussian basis and medium-size k-point sampling, and find good agreement with experimental measurements.Comment: 7 pages, 4 figures, 1 tabl

Center Variation in the Delivery of Indicated Late Preterm Births

Evidence for optimal timing of delivery for some pregnancy complications at late preterm gestation is limited. The purpose of this study was to identify center variation of indicated late preterm births

Predictors of Bronchopulmonary Dysplasia

Although significant advances in respiratory care have been made in neonatal medicine, bronchopulmonary dysplasia (BPD) remains the most common serious pulmonary morbidity in premature infants. The development of BPD is the result of the complex interactions between multiple perinatal and postnatal factors. Early identification of infants at the most risk of developing BPD through the use of estimators and models may allow a targeted approach at reducing BPD in the future

Characteristics of patients who die of necrotizing enterocolitis

Objective:Necrotizing enterocolitis (NEC) is associated with high morbidity and mortality among infants admitted for intensive care. The factors associated with mortality and catastrophic presentation remain poorly understood. Our objective was to describe the factors associated with mortality in infants with NEC and to quantify the degree to which catastrophic presentation contributes to mortality in infants with NEC. Catastrophic NEC was defined before data analysis as NEC that led to death within 7 days of diagnosis.Study Design:We performed a retrospective review of the Pediatrix's Clinical Data Warehouse (1997 to 2009, n=560,227) to compare the demographic, therapeutic and outcome characteristics of infants who survived NEC vs those who died. Associations were tested by bivariate and multivariate analysis.Result:We compared the 5594 infants diagnosed with NEC and who were discharged home with 1505 infants diagnosed with NEC who died. In multivariate analysis, the factors associated with death (P<0.01 in analysis) were lower estimated gestational age, lower birth weight, treatment with assisted ventilation on the day of diagnosis of NEC, treatment with vasopressors at the time of diagnosis, and Black race. Patients who received only ampicillin and gentamicin on the day of diagnosis were less likely to die. Two-thirds of NEC deaths occurred quickly (<7 days from diagnosis), with a median time of death of one day from time of diagnosis. Infants who died within 7 days of diagnosis had a higher birth weight, more often were on vasopressors and high frequency ventilation at the time of diagnosis compared with patients who died at 7 or more days. Although mortality decreased with increasing gestational age, the proportion of deaths that occurred within 7 days was relatively consistent (65 to 75% of the patients who died) across all gestational ages.Conclusion:Mortality among infants who have NEC remains high and infants who die of NEC commonly (66%) die quickly. Most of the factors associated with mortality are related to immaturity, low birth weight and severity of illness

Association between furosemide in premature infants and sensorineural hearing loss and nephrocalcinosis: a systematic review

Abstract Furosemide is a potent loop diuretic commonly and variably used by neonatologists to improve oxygenation and lung compliance in premature infants. There are several safety concerns with use of furosemide in premature infants, specifically the risk of sensorineural hearing loss (SNHL), and nephrocalcinosis/nephrolithiasis (NC/NL). We conducted a systematic review of all trials and observational studies examining the association between these outcomes with exposure to furosemide in premature infants. We searched MEDLINE, EMBASE, CINAHL, and clinicaltrials.gov . We included studies reporting either SNHL or NC/NL in premature infants (< 37 weeks completed gestational age) who received at least one dose of enteral or intravenous furosemide. Thirty-two studies met full inclusion criteria for the review, including 12 studies examining SNHL and 20 studies examining NC/NL. Only one randomized controlled trial was identified in this review. We found no evidence that furosemide exposure increases the risk of SNHL or NC/NL in premature infants, with varying quality of studies and found the strength of evidence for both outcomes to be low. The most common limitation in these studies was the lack of control for confounding factors. The evidence for the risk of SNHL and NC/NL in premature infants exposed to furosemide is low. Further randomized controlled trials of furosemide in premature infants are urgently needed to adequately assess the risk of SNHL and NC/NL, provide evidence for improved FDA labeling, and promote safer prescribing practices.https://deepblue.lib.umich.edu/bitstream/2027.42/146523/1/40748_2018_Article_92.pd

Development of a proxy-reported pulmonary outcome scale for preterm infants with bronchopulmonary dysplasia

<p>Abstract</p> <p>Background</p> <p>To develop an accurate, proxy-reported bedside measurement tool for assessment of the severity of bronchopulmonary dysplasia (also called chronic lung disease) in preterm infants to supplement providers' current biometric measurements of the disease.</p> <p>Methods</p> <p>We adapted Patient-Reported Outcomes Measurement Information System (PROMIS) methodology to develop the Proxy-Reported Pulmonary Outcomes Scale (PRPOS). A multidisciplinary group of registered nurses, nurse practitioners, neonatologists, developmental specialists, and feeding specialists at five academic medical centers participated in the PRPOS development, which included five phases: (1) identification of domains, items, and responses; (2) item classification and selection using a modified Delphi process; (3) focus group exploration of items and response options; (4) cognitive interviews on a preliminary scale; and (5) final revision before field testing.</p> <p>Results</p> <p>Each phase of the process helped us to identify, classify, review, and revise possible domains, questions, and response options. The final items for field testing include 26 questions or observations that a nurse assesses before, during, and after routine care time and feeding.</p> <p>Conclusions</p> <p>We successfully created a prototype scale using modified PROMIS methodology. This process can serve as a model for the development of proxy-reported outcomes scales in other pediatric populations.</p

Risk Factors and In-Hospital Outcomes following Tracheostomy in Infants

To describe the epidemiology, risk factors, and in-hospital outcomes of tracheostomy in infants in the neonatal intensive care unit (NICU)

Prevention of chronic lung disease

Considerable effort has been devoted to the development of strategies to reduce the incidence of chronic lung disease, including use of medications, nutritional therapies, and respiratory care practices. Unfortunately, most of these strategies have not been successful. To date, the only two treatments developed specifically to prevent CLD whose efficacy is supported by evidence from randomized, controlled trials are the parenteral administration of vitamin A and corticosteroids. Two other therapies, the use of caffeine for the treatment of apnea of prematurity and aggressive phototherapy for the treatment of hyperbilirubinemia were evaluated for the improvement of other outcomes and found to reduce CLD. Cohort studies suggest that the use of CPAP as a strategy for avoiding mechanical ventilation might also be beneficial. Other therapies reduce lung injury in animal models but do not appear to reduce CLD in humans. The benefits of the efficacious therapies have been modest, with an absolute risk reduction in the 7–11% range. Further preventive strategies are needed to reduce the burden of this disease. However, each will need to be tested in randomized, controlled trials, and the expectations of new therapies should be modest reductions of the incidence of the disease

Association between oral sildenafil dosing, predicted exposure, and systemic hypotension in hospitalised infants

Abstract Background The relationship between sildenafil dosing, exposure, and systemic hypotension in infants is incompletely understood. Objectives The aim of this study was to characterise the relationship between predicted sildenafil exposure and hypotension in hospitalised infants. Methods We extracted information on sildenafil dosing and clinical characteristics from electronic health records of 348 neonatal ICUs from 1997 to 2013, and we predicted drug exposure using a population pharmacokinetic model. Results We identified 232 infants receiving sildenafil at a median dose of 3.2 mg/kg/day (2.0, 6.0). The median steady-state area under the concentration–time curve over 24 hours (AUC 24,SS ) and maximum concentration of sildenafil (C max,SS,SIL ) were 712 ng×hour/ml (401, 1561) and 129 ng/ml (69, 293), respectively. Systemic hypotension occurred in 9% of the cohort. In multivariable analysis, neither dosing nor exposure were associated with systemic hypotension: odds ratio=0.96 (95% confidence interval: 0.81, 1.14) for sildenafil dose; 0.87 (0.59, 1.28) for AUC 24,SS ; 1.19 (0.78, 1.82) for C max,SS,SIL . Conclusions We found no association between sildenafil dosing or exposure with systemic hypotension. Continued assessment of sildenafil’s safety profile in infants is warranted