Implementation of the Neonatal Sepsis Calculator in Early-Onset Sepsis and Maternal Chorioamnionitis.

BACKGROUND: Utilization of the neonatal sepsis calculator published by Kaiser Permanente is rapidly increasing. This freely available online tool can be used in assessment of early-onset sepsis (EOS) in newborns 34 weeks' gestation or more based on maternal risk factors and neonatal examination. However, many hospitals lack standard guidelines for its use, leading to provider discomfort with practice change. PURPOSE: The goal of this project was to study the antibiotic use rate for EOS at a level III neonatal intensive care unit and create standardized guidelines and staff education for using the sepsis calculator. Our ultimate goal was to decrease antibiotic use for EOS in newborns 34 weeks' gestation or more. METHODS: A standard quality improvement Plan-Do-Study-Act (PDSA) model was utilized with a plan to study the problem, implement the intervention, and test again for improvement. The primary outcome of interest was a decrease in the use of antibiotics for EOS in neonates 34 weeks' gestation or more. RESULTS: Over a 4-month period, prior to sepsis calculator implementation, antibiotic use for suspected EOS was 11% and blood culture was done on 14.8% of live births. After implementation of the sepsis calculator and completion of the PDSA cycle, sepsis calculator use was greater than 95%, antibiotic use dropped significantly to 5% (P = .00069), and blood culture use dropped to 7.6% (P = .00046). IMPLICATIONS FOR PRACTICE: Staff education and systematic intervention using a PDSA model can significantly impact patient care, decreasing the administration of antibiotics to infants at risk for sepsis. IMPLICATIONS FOR RESEARCH: Future research is needed to decrease antibiotic use in premature infants less than 34 weeks' gestation with similar risk factors and clinical features.Video Abstract available at https://journals.na.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?videoId=34&autoPlay=true.

Mupirocin for Staphylococcus aureus Decolonization of Infants in Neonatal Intensive Care Units.

: media-1vid110.1542/5849573989001PEDS-VA_2018-1565Video Abstract BACKGROUND AND OBJECTIVES: Staphylococcus aureus (SA) is the second leading cause of late-onset sepsis among infants in the NICU. Because colonization of nasal mucosa and/or skin frequently precedes invasive infection, decolonization strategies, such as mupirocin application, have been attempted to prevent clinical infection, but data supporting this approach in infants are limited. We conducted a phase 2 multicenter, open-label, randomized trial to assess the safety and efficacy of intranasal plus topical mupirocin in eradicating SA colonization in critically ill infants. METHODS: Between April 2014 and May 2016, infants <24 months old in the NICU at 8 study centers underwent serial screening for nasal SA. Colonized infants who met eligibility criteria were randomly assigned to receive 5 days of mupirocin versus no mupirocin to the intranasal, periumbilical, and perianal areas. Mupirocin effects on primary (day 8) and persistent (day 22) decolonization at all three body sites were assessed. RESULTS: A total of 155 infants were randomly assigned. Mupirocin was generally well tolerated, but rashes (usually mild and perianal) occurred significantly more often in treated versus untreated infants. Primary decolonization occurred in 62 of 66 (93.9%) treated infants and 3 of 64 (4.7%) control infants (P < .001). Twenty-one of 46 (45.7%) treated infants were persistently decolonized compared with 1 of 48 (2.1%) controls (P < .001). CONCLUSIONS: Application of mupirocin to multiple body sites was safe and efficacious in eradicating SA carriage among infants in the NICU; however, after 2 to 3 weeks, many infants who remained hospitalized became recolonized.

Newborn Sequencing in Genomic Medicine and Public Health.

The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing in newborns for both diagnosis and screening.

Rapid whole genome sequencing and precision neonatology.

Traditionally, genetic testing has been too slow or perceived to be impractical to initial management of the critically ill neonate. Technological advances have led to the ability to sequence and interpret the entire genome of a neonate in as little as 26 h. As the cost and speed of testing decreases, the utility of whole genome sequencing (WGS) of neonates for acute and latent genetic illness increases. Analyzing the entire genome allows for concomitant evaluation of the currently identified 5588 single gene diseases. When applied to a select population of ill infants in a level IV neonatal intensive care unit, WGS yielded a diagnosis of a causative genetic disease in 57% of patients. These diagnoses may lead to clinical management changes ranging from transition to palliative care for uniformly lethal conditions for alteration or initiation of medical or surgical therapy to improve outcomes in others. Thus, institution of 2-day WGS at time of acute presentation opens the possibility of early implementation of precision medicine. This implementation may create opportunities for early interventional, frequently novel or off-label therapies that may alter disease trajectory in infants with what would otherwise be fatal disease. Widespread deployment of rapid WGS and precision medicine will raise ethical issues pertaining to interpretation of variants of unknown significance, discovery of incidental findings related to adult onset conditions and carrier status, and implementation of medical therapies for which little is known in terms of risks and benefits. Despite these challenges, precision neonatology has significant potential both to decrease infant mortality related to genetic diseases with onset in newborns and to facilitate parental decision making regarding transition to palliative care.

Effects of whole body therapeutic hypothermia on gastrointestinal morbidity and feeding tolerance in infants with hypoxic ischemic encephalopathy.

Objective. This retrospective cohort study evaluated the effects of whole body therapeutic hypothermia (WBTH) on gastrointestinal (GI) morbidity and feeding tolerance in infants with moderate-to-severe hypoxic ischemic encephalopathy (HIE). Study Design. Infants ≥ 35 weeks gestational age and ≥1800 grams birth weight with moderate-to-severe HIE treated from 2000 to 2012 were compared. 68 patients had documented strictly defined criteria for WBTH: 32 historical control patients did not receive WBTH (non-WBTH) and 36 cohort patients received WBTH. Result. More of the non-WBTH group infants never initiated enteral feeds (28% versus 6%; P = 0.02), never reached full enteral feeds (38% versus 6%, P = 0.002), and never reached full oral feeds (56% versus 19%, P = 0.002). Survival analyses demonstrated that the WBTH group reached full enteral feeds (median time: 11 versus 9 days; P = 0.02) and full oral feeds (median time: 19 versus 10 days; P = 0.01) sooner. The non-WBTH group had higher combined outcomes of death and gastric tube placement (47% versus 11%; P = 0.001) and death and gavage feeds at discharge (44% versus 11%; P = 0.005). Conclusion. WBTH may have beneficial effects on GI morbidity and feeding tolerance for infants with moderate-to-severe HIE.

Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units.

Monogenic diseases are frequent causes of neonatal morbidity and mortality, and disease presentations are often undifferentiated at birth. More than 3500 monogenic diseases have been characterized, but clinical testing is available for only some of them and many feature clinical and genetic heterogeneity. Hence, an immense unmet need exists for improved molecular diagnosis in infants. Because disease progression is extremely rapid, albeit heterogeneous, in newborns, molecular diagnoses must occur quickly to be relevant for clinical decision-making. We describe 50-hour differential diagnosis of genetic disorders by whole-genome sequencing (WGS) that features automated bioinformatic analysis and is intended to be a prototype for use in neonatal intensive care units. Retrospective 50-hour WGS identified known molecular diagnoses in two children. Prospective WGS disclosed potential molecular diagnosis of a severe GJB2-related skin disease in one neonate; BRAT1-related lethal neonatal rigidity and multifocal seizure syndrome in another infant; identified BCL9L as a novel, recessive visceral heterotaxy gene (HTX6) in a pedigree; and ruled out known candidate genes in one infant. Sequencing of parents or affected siblings expedited the identification of disease genes in prospective cases. Thus, rapid WGS can potentially broaden and foreshorten differential diagnosis, resulting in fewer empirical treatments and faster progression to genetic and prognostic counseling.

Selective Toll--like receptor expression in human fetal lung.

Toll-like receptors (TLRs) are critical components of the innate immune system, acting as pattern recognition molecules and triggering an inflammatory response. TLR associated gene products are of interest in modulating inflammatory-related pulmonary diseases of the neonate. The ontogeny of TLR-related genes in human fetal lung has not been previously described and could elucidate additional functions and identify strategies for attenuating the effects of fetal inflammation. We examined the expression of 84 TLR-related genes on 23 human fetal lung samples from three groups with estimated ages of 60 (57-59 d), 90 (89-91 d), and 130 (117-154 d) d. By using a false detection rate algorithm, we identified 32 genes displaying developmental regulation with TLR2 having the greatest up-regulation of TLR genes (9.2-fold increase) and TLR4 unchanged. We confirmed the TLR2 up-regulation by examining an additional 133 fetal lung tissue samples with a fluorogenic polymerase chain reaction assay (TaqMan) and found an exponential best-fit curve during the study time. The best-fit curve predicts a 6.1-fold increase from 60 to 130 d. We conclude that TLR2 is developmentally expressed from the early pseudoglandular stage of lung development to the canalicular stage.