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.

Updates in Late-Onset Sepsis: Risk Assessment, Therapy, and Outcomes.

Neonatal late-onset sepsis (LOS) continues to threaten morbidity and mortality in the NICU and poses ongoing diagnostic and therapeutic challenges. Early recognition of clinical signs, rapid evaluation, and prompt initiation of treatment are critical to prevent life-threatening deterioration. Preterm infants-born at ever-decreasing gestational ages-are at particularly high risk for life-long morbidities and death. This changing NICU population necessitates continual reassessments of diagnostic and preventive measures and evidence-based treatment for LOS. The clinical presentation of LOS is varied and nonspecific. Despite ongoing research, reliable, specific laboratory biomarkers facilitating early diagnosis are lacking. These limitations drive an ongoing practice of liberal initiation of empiric antibiotics among infants with suspected LOS. Subsequent promotion of multidrug-resistant microorganisms threatens the future of antimicrobial therapy and puts preterm and chronically ill infants at even higher risk of nosocomial infection. Efforts to identify adjunctive therapies counteracting sepsis-driven hyperinflammation and sepsis-related functional immunosuppression are ongoing. However, most approaches have either failed to improve LOS prognosis or are not yet ready for clinical application. This article provides an overview of the epidemiology, risk factors, diagnostic tools, and treatment options of LOS in the context of increasing numbers of extremely preterm infants. It addresses the question of whether LOS could be identified earlier and more precisely to allow for earlier and more targeted therapy and discusses rational approaches to antibiotic therapy to avoid overuse. Finally, this review elucidates the necessity of long-term follow-up of infants with a history of LOS.

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.