Bacterial meningitis in a quaternary NICU: A multiyear retrospective study.

Bacterial meningitis causes significant morbidity and mortality in infants. Lumbar punctures are often deferred until the results of blood cultures are known and sometimes not considered, making this population susceptible to a missed diagnosis. There are few studies describing the epidemiology of neonatal meningitis in quaternary neonatal intensive care unit settings.

Sepsis Huddles in the Neonatal Intensive Care Unit: A Retrospective Cohort Study of Late-onset Infection Recognition and Severity Assessment.

Objective: To analyze relationships between provider-documented signs prompting sepsis evaluations, assessments of illness severity, and late-onset infection (LOI).

Study Design: Retrospective cohort study of all infants receiving a sepsis huddle in conjunction with a LOI evaluation. Participants were ≥3 days old and admitted to a level IV neonatal intensive care unit (NICU) from September 2018 through May 2021.

Dual-site blood culture yield and time to positivity in neonatal late-onset sepsis.

Objective: To determine whether culture yield and time to positivity (TTP) differ between peripheral and central vascular catheter-derived blood cultures (BCx) in neonatal intensive care unit (NICU) patients evaluated for late-onset sepsis.

Design: Single-centre, retrospective, observational study.

Setting: Level IV NICU.

Acute Kidney Injury Associated with Late-Onset Neonatal Sepsis: A Matched Cohort Study.

Objectives: To determine incidence and severity of acute kidney injury (AKI) within 7 days of sepsis evaluation and to assess AKI duration and the association between AKI and 30-day mortality.

Study Design: Retrospective, matched cohort study in a single-center level IV neonatal intensive care unit. Eligible infants underwent sepsis evaluations at ≥72 hours of age during calendar years 2013-2018.

Derivation of a metabolic signature associated with bacterial meningitis in infants.

Background: Diagnosis of bacterial meningitis (BM) is challenging in newborn infants. Presently, biomarkers of BM have limited diagnostic accuracy. Analysis of cerebrospinal fluid (CSF) metabolites may be a useful diagnostic tool in BM.

Performance of Pediatric Systemic Inflammatory Response Syndrome and Organ Dysfunction Criteria in Late-Onset Sepsis in a Quaternary Neonatal Intensive Care Unit: A Case-Control Study.

Objectives: To evaluate accuracy of systemic inflammatory response syndrome (SIRS) criteria in identifying culture-proven late-onset neonatal sepsis and to assess prevalence of organ dysfunction and its relationship with SIRS criteria.

Study Design: This was a retrospective case-control study of patients in the Children's Hospital of Philadelphia level IV neonatal intensive care unit undergoing sepsis evaluations (concurrent blood culture and antibiotics). During calendar years 2016-2017, 77 case and 77 control sepsis evaluations were identified.

Neonatal sepsis registry: Time to antibiotic dataset.

This article describes the process of extracting electronic health record (EHR) data into a format that supports analyses related to the timeliness of antibiotic administration. The de-identified data that accompanies this article were collected from a cohort of infants who were evaluated for possible sepsis in the Neonatal Intensive Care Unit (NICU) at the Children's Hospital of Philadelphia (CHOP). The interpretation of findings from these data are reported in a separate manuscript [1].

The Influence of Gender and Underrepresented Minority Status on Medical Student Ranking of Residency Programs.

Background: Physician diversity is linked to improved quality of care of diverse patient populations. The transition from medical school to residency is an opportunity to improve and increase workforce diversity in all specialties. However, there is limited published literature on the factors contributing to the ranking of residency programs on women and underrepresented minorities (URMs).

Surviving Sepsis in a Referral Neonatal Intensive Care Unit: Association between Time to Antibiotic Administration and In-Hospital Outcomes.

Objective: To determine if time to antibiotic administration is associated with mortality and in-hospital outcomes in a neonatal intensive care unit (NICU) population.

Study Design: We conducted a prospective evaluation of infants with suspected sepsis between September 2014 and February 2018; sepsis was defined as clinical concern prompting blood culture collection and antibiotic administration. Time to antibiotic administration was calculated from time of sepsis identification, defined as the order time of either blood culture or an antibiotic, to time of first antibiotic administration.

Machine learning models for early sepsis recognition in the neonatal intensive care unit using readily available electronic health record data.

Background: Rapid antibiotic administration is known to improve sepsis outcomes, however early diagnosis remains challenging due to complex presentation. Our objective was to develop a model using readily available electronic health record (EHR) data capable of recognizing infant sepsis at least 4 hours prior to clinical recognition.

Methods And Findings: We performed a retrospective case control study of infants hospitalized ≥48 hours in the Neonatal Intensive Care Unit (NICU) at the Children's Hospital of Philadelphia between September 2014 and November 2017 who received at least one sepsis evaluation before 12 months of age.

Elevations of novel cytokines in bacterial meningitis in infants.

Background: Bacterial meningitis is challenging to diagnose in infants, especially in the common setting of antibiotic pre-treatment, which diminishes yield of cerebrospinal fluid (CSF) cultures. Prior studies of diagnostic markers have not demonstrated sufficient accuracy. Interleukin-23 (IL-23), interleukin-18 (IL-18) and soluble receptor for advanced glycation end products (sRAGE) possess biologic plausibility, and may be useful as diagnostic markers in bacterial meningitis.

Neonatal Meningitis: Overcoming Challenges in Diagnosis, Prognosis, and Treatment with Omics.

Neonatal meningitis is a devastating condition. Prognosis has not improved in decades, despite the advent of improved antimicrobial therapy and heightened index of suspicion among clinicians caring for affected infants. One in ten infants die from meningitis, and up to half of survivors develop significant lifelong complications, including seizures, impaired hearing and vision, and delayed or arrested development of such basic skills as talking and walking.

Cerebrospinal fluid cytokines in the diagnosis of bacterial meningitis in infants.

Background: Bacterial meningitis poses diagnostic challenges in infants. Antibiotic pretreatment and low bacterial density diminish cerebrospinal fluid (CSF) culture yield, while laboratory parameters do not reliably identify bacterial meningitis. Pro and anti-inflammatory cytokines are elevated in bacterial meningitis and may be useful diagnostic adjuncts when CSF cultures are negative.

Impaired Activity of Blood Coagulant Factor XIII in Patients with Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal (GI) medical/surgical emergency of the newborn and a leading cause of preterm neonate morbidity and mortality. NEC is a challenge to diagnose since it often shares similar clinical features with neonatal sepsis. In the present study, plasma protein profiling was compared among NEC, sepsis and control cohorts using gel electrophoresis, immunoblot and mass spectrometry.

Risk factors associated with laboratory-confirmed bloodstream infections in a tertiary neonatal intensive care unit.

Background: Bloodstream infections (BSI) remain a leading cause of morbidity and mortality among infants admitted to neonatal intensive care units (NICUs). At the time of evaluation for suspected BSI, presenting signs may be nonspecific. We sought to determine the clinical signs and risk factors associated with laboratory-confirmed BSI among infants evaluated for late-onset sepsis in a tertiary NICU.

A data-driven algorithm integrating clinical and laboratory features for the diagnosis and prognosis of necrotizing enterocolitis.

Background: Necrotizing enterocolitis (NEC) is a major source of neonatal morbidity and mortality. Since there is no specific diagnostic test or risk of progression model available for NEC, the diagnosis and outcome prediction of NEC is made on clinical grounds. The objective in this study was to develop and validate new NEC scoring systems for automated staging and prognostic forecasting.

Urine protein biomarkers for the diagnosis and prognosis of necrotizing enterocolitis in infants.

Objectives: To test the hypothesis that an exploratory proteomics analysis of urine proteins with subsequent development of validated urine biomarker panels would produce molecular classifiers for both the diagnosis and prognosis of infants with necrotizing enterocolitis (NEC).

Study Design: Urine samples were collected from 119 premature infants (85 NEC, 17 sepsis, 17 control) at the time of initial clinical concern for disease. The urine from 59 infants was used for candidate biomarker discovery by liquid chromatography/mass spectrometry.

A novel urine peptide biomarker-based algorithm for the prognosis of necrotising enterocolitis in human infants.

Objective: Necrotising enterocolitis (NEC) is a major source of neonatal morbidity and mortality. The management of infants with NEC is currently complicated by our inability to accurately identify those at risk for progression of disease prior to the development of irreversible intestinal necrosis. We hypothesised that integrated analysis of clinical parameters in combination with urine peptide biomarkers would lead to improved prognostic accuracy in the NEC population.

Clinical features of three girls with mosaic genome-wide paternal uniparental isodisomy.

Here we describe three subjects with mosaic genome-wide paternal uniparental isodisomy (GWpUPD) each of whom presented initially with overgrowth, hemihyperplasia (HH), and hyperinsulinism (HI). Due to the severity of findings and the presence of additional features, SNP array testing was performed, which demonstrated mosaic GWpUPD. Comparing these individuals to 10 other live-born subjects reported in the literature, the predominant phenotype is that of pUPD11 and notable for a very high incidence of tumor development.

Traumatic lumbar punctures in infants hospitalized in the neonatal intensive care unit.

Traumatic lumbar punctures occur frequently in the neonatal intensive care unit, making the interpretation of cerebrospinal fluid values difficult. We report correction factors for cerebrospinal fluid protein and white blood cells in the face of red blood cell contamination. These correction factors should facilitate the diagnosis of bacterial meningitis in highrisk hospitalized infants.

Lumbar puncture in the neonate: challenges in decision making and interpretation.

Multiple studies have provided normative ranges for cerebrospinal fluid (CSF) parameters in term and preterm infants and described changes with advancing postnatal age, as well as in special circumstances, such as traumatic lumbar puncture (LP), previous antibiotic administration, seizures, and concomitant infections at other sites. Although guidelines exist for the interpretation of CSF parameters in neonates, there appears to be no single combination of parameters that conclusively excludes meningitis. It remains important for clinicians to perform LPs early in the course of illness, ideally before the administration of antibiotic therapy.

Can broad-range 16S ribosomal ribonucleic acid gene polymerase chain reactions improve the diagnosis of bacterial meningitis? A systematic review and meta-analysis.

Study Objective: We aim to evaluate the accuracy of the broad-range 16S polymerase chain reaction test in the diagnosis of bacterial meningitis through a systematic review and meta-analysis.

Methods: We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Registry, using the Medical Subject Headings terms "polymerase chain reaction," "RNA, ribosomal, 16S," and "bacterial meningitis." For our primary analysis, we examined the 16S polymerase chain reaction in culture-proven bacterial meningitis.

Cerebrospinal fluid reference ranges in term and preterm infants in the neonatal intensive care unit.

Objective: To determine reference ranges of cerebrospinal fluid (CSF) laboratory findings in term and preterm infants in the neonatal intensive care unit.

Study Design: Data were collected prospectively as part of a multisite study of infants aged <6 months undergoing lumbar puncture for evaluation of suspected sepsis. Infants with a red blood cell count >500 cells/μL or a known cause of CSF pleocytosis were excluded from the analysis.

New technologies for the rapid diagnosis of neonatal sepsis.

Purpose Of Review: To present recent literature on novel diagnostic tests in neonatal sepsis.

Recent Findings: Our review of technologies for the rapid diagnosis of neonatal sepsis includes new adaptations of time-honored tests as well as advances on the forefront of medicine. A recent study demonstrates that age-specific likelihood values for the complete blood count may determine risk of infection.