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. Data were extracted from standardized sepsis huddle notes in the electronic health record, including clinical signs prompting LOI evaluations, illness severity assessments (from least to most severe: green, yellow, and red), and management plans. To analyze relationships of sepsis huddle characteristics with the detection of culture-confirmed LOI (bacteremia, urinary tract infection, or meningitis), we utilized diagnostic test statistics, area under the receiver-operator characteristic analyses, and multivariable logistic regression. RESULTS: We identified 1209 eligible sepsis huddles among 604 infants. There were 111 culture-confirmed LOI episodes (9% of all huddles). Twelve clinical signs of infection poorly distinguished infants with and without LOI, with sensitivity for each ranging from 2% to 36% and area under the receiver-operator characteristic ranging 0.49-0.53. Multivariable logistic regression identified increasing odds of infection with higher perceived illness severity at the time of sepsis huddle, adjusted for gestational age and receipt of intensive care supports. CONCLUSIONS: Clinical signs prompting sepsis huddles were nonspecific and not predictive of concurrent LOI. Higher perceived illness severity was associated with presence of infection, despite some misclassification based on objective criteria. In level IV NICUs, antimicrobial stewardship through development of criteria for antibiotic noninitiation may be challenging, as presenting signs of LOI are similar among infants with and without confirmed infection.

Effect of Minimization of Early Blood Sampling Losses Among Extremely Premature Neonates: A Randomized Clinical Trial.

OBJECTIVE: To evaluate the effect of blood sampling stewardship on transfusion requirements among infants born extremely preterm. STUDY DESIGN: In this single-center, randomized controlled trial (RCT), infants born at <28 weeks of gestation and birth weight of <1000 g were randomized at 24 hours of age to two different blood sampling approaches: restricted sampling (RS) vs conventional sampling (CS). The stewardship intervention in the RS group included targeted reduction in blood sampling volume and frequency and point of care testing methods in the first 6 weeks after birth. Both groups received early recombinant erythropoietin from day three of age. Primary outcome was the rate of early red blood cell (RBC) transfusions in the first six postnatal weeks. RESULTS: A total of 102 infants (mean gestational age: 26 weeks; birth weight: 756 g) were enrolled. Fidelity to the sampling protocol was achieved in 95% of the infants. Sampling losses in the first 6 weeks were significantly lower in the RS group (16.8 ml/kg vs 23.6 ml/kg, P < .001). The RS group had a significantly lower rate of early postnatal RBC transfusions (41% vs 73%, RR: 0.56 [0.39-0.81], P = .001). The hazard of needing a transfusion during neonatal intensive care unit (NICU) stay was reduced by 55% by RS. Mortality and neonatal morbidities were similar between the two groups. CONCLUSION: Minimization of blood sampling losses by approximately one-third in the first 6 weeks after birth leads to substantial reduction in the early red blood cell transfusion rate in infants born extremely preterm and weighing <1000 g at birth. TRIAL REGISTRATION: http://www.ctri.nic.in (CTRI/2020/01/022  964).

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. Exposed infants (cases) were those with culture-proven sepsis and antimicrobial duration ≥5 days. Nonexposed infants (controls) were matched 1:1 to exposed infants based on gestational and corrected gestational age, and had negative sepsis evaluations with antibiotic durations <48 hours. AKI was defined by modified neonatal Kidney Disease Improving Global Outcomes criteria. Statistical analysis included Mann-Whitney and χ2 tests, multivariable logistic regression, and Kaplan-Meier time-to-event analysis. RESULTS: Among 203 episodes of late-onset sepsis, 40 (20%) developed AKI within 7 days after evaluation, and among 193 episodes with negative cultures, 16 (8%) resulted in AKI (P = .001). Episodes of sepsis also led to greater AKI severity, compared with nonseptic episodes (P = .007). The timing of AKI onset and AKI duration did not differ between groups. Sepsis was associated with increased odds of developing AKI (aOR, 3.0; 95% CI, 1.5-6.2; P = .002). AKI was associated with increased 30-day mortality (aOR, 4.5; 95% CI, 1.3-15.6; P = .017). CONCLUSIONS: Infants with late-onset sepsis had increased odds of AKI and greater AKI severity within 7 days of sepsis evaluation, compared with age-matched infants without sepsis. AKI was independently associated with increased 30-day mortality. Strategies to mitigate AKI in critically ill neonates with sepsis may improve outcomes.

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. Cases included infants who had sepsis evaluations with positive blood cultures and antibiotic duration ≥7 days. Controls were matched by gestational and postmenstrual age, and had sepsis evaluations with negative blood cultures and antibiotic duration ≤48 hours. SIRS criteria were determined at time of sepsis evaluation, and organ dysfunction evaluated in the 72 hours following sepsis evaluation. Statistical analysis included descriptive statistics, Mann-Whitney tests, and χ2 (Fisher exact) tests. RESULTS: At time of sepsis evaluation, 42% of cases and 26% of controls met SIRS criteria. Among infants of ≤37 weeks postmenstrual age, SIRS criteria were met in only 17% of sepsis evaluations (4 of 23 in both cases and controls). Test characteristics for SIRS at diagnosis of culture-proven sepsis included sensitivity 42% and specificity 74%. Cases had higher rates of new organ dysfunction within 72 hours (40% vs 21%); however, 58% of cases developing organ dysfunction did not meet SIRS criteria at time of sepsis evaluation. Of 6 deaths (all cases with organ dysfunction), 2 did not meet SIRS criteria at sepsis evaluation. CONCLUSIONS: SIRS criteria did not accurately identify culture-proven late-onset sepsis, with poorest accuracy in preterm infants. SIRS criteria did not predict later organ dysfunction or mortality.

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. We used linear models with generalized estimating equations to determine the association between time to antibiotic administration and mortality, ventilator-free and inotrope-free days, and NICU length of stay in patients with culture-proven sepsis. RESULTS: Among 1946 sepsis evaluations, we identified 128 episodes of culture-proven sepsis in 113 infants. Among them, prolonged time to antibiotic administration was associated with significantly increased risk of mortality at 14 days (OR, 1.47; 95% CI, 1.15-1.87) and 30 days (OR, 1.47; 95% CI, 1.11-1.94) as well as fewer inotrope-free days (incidence rate ratio, 0.91; 95% CI, 0.84-0.98). No significant associations with ventilator-free days or NICU length of stay were demonstrated. CONCLUSIONS: Among infants with sepsis, delayed time to antibiotic administration was an independent risk factor for death and prolonged cardiovascular dysfunction. Further study is needed to define optimal timing of antimicrobial administration in high-risk NICU populations.

Effect of Umbilical Cord Blood Sampling versus Admission Blood Sampling on Requirement of Blood Transfusion in Extremely Preterm Infants: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of blood sampling from the placental end of the umbilical cord compared with initial blood sampling from neonates, on the need for first packed red blood cell transfusion in extremely preterm infants. We hypothesized that cord blood sampling could delay the time to first blood transfusion. STUDY DESIGN: In this single-center, assessor blind, randomized controlled trial, we included extremely low birth weight neonates <28 weeks of gestational age at birth. Five milliliter of blood for initial laboratory investigations was collected either from the placental end of the umbilical cord (study group) or from the neonate upon neonatal intensive care unit admission (control group). Both groups received similar anemia prevention strategies. The primary outcome was the time (in days) to the first packed red blood cell transfusion, and was compared using survival analysis. RESULTS: Eighty neonates were enrolled. The time to first transfusion was significantly delayed in the cord sampling group (30 vs 14 days, hazard ratio: 0.44, [95% CI 0.27-0.72], P < .001). Fewer neonates in the cord sampling group were transfused in the first 28 days of life (30% vs 75%, P < .001). Overall transfusion requirements and other clinical outcomes were similar in the groups. CONCLUSIONS: Initial blood sampling from placental end of umbilical cord, when combined with anemia prevention strategies, significantly prolonged the time to first transfusion and reduced the need for early transfusions among extremely premature neonates. TRIAL REGISTRATION: Ctri.nic.in/ (CTRI/2017/04/008320).

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. METHODS: This prospective cohort study included infants >3 days of age admitted to a level 4 NICU from July 2006 to October 2009 for whom a blood culture was drawn for suspected sepsis. Clinicians documented presenting signs at the time of culture. Laboratory-confirmed BSI was defined as per the National Healthcare Safety Network. Multivariate analyses were performed using a logistic regression random effects model. RESULTS: Six-hundred and eighty eligible episodes of suspected BSI were recorded in 409 infants. Enteral contrast within the preceding 48 hours was the most significant risk factor for laboratory-confirmed BSI [Odds Ratio: 9.58 (95% confidence interval: 2.03-45.19)] followed by presence of a central venous catheter. Apnea and hypotension were the most strongly associated presenting signs. CONCLUSION: Among infants evaluated in a tertiary NICU, recent exposure to enteral contrast was associated with increased odds of developing BSI. Apnea and hypotension were the most strongly associated clinical signs of infection.

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.

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. RESULTS: A total of 318 infants met the inclusion criteria. Of these, 148 infants (47%) were preterm, and 229 (72%) received antibiotics before undergoing lumbar puncture. The upper reference limit of the CSF white blood cell (WBC) count was 12 cells/µL in preterm infants and 14 cells/µL in term infants. CSF protein levels were significantly higher in preterm infants (upper reference limit, 209 mg/dL vs 159 mg/dL in term infants; P < .001), and declined with advancing postnatal age in both groups (preterm, P = .008; term, P < .001). CSF glucose levels did not differ in term and preterm infants. Antibiotic exposure did not significantly affect CSF WBC, protein, or glucose values. CONCLUSIONS: CSF WBC counts are not significantly different in preterm and term infants. CSF protein levels are higher and decline more slowly with postnatal age in preterm infants compared with term infants. This study provides CSF reference ranges for hospitalized preterm and term infants, particularly in the first month of life.