OBJECTIVES: To determine the epidemiology, microbiology, and associated outcomes of late-onset sepsis among very preterm infants using a large and nationally representative cohort of NICUs across the United States.

METHODS: Prospective observational study of very preterm infants born 401 to 1500 g and/or 22 to 29 weeks' gestational age (GA) from January 1, 2018, to December 31, 2020, who survived >3 days in 774 participating Vermont Oxford Network centers. Late-onset sepsis was defined as isolation of a pathogenic bacteria from blood and/or cerebrospinal fluid, or fungi from blood, obtained >3 days after birth. Demographics, clinical characteristics, and outcomes were compared between infants with and without late-onset sepsis.

RESULTS: Of 118 650 infants, 10 501 (8.9%) had late-onset sepsis for an incidence rate of 88.5 per 1000 (99% confidence interval [CI] [86.4-90.7]). Incidence was highest for infants born ≤23 weeks GA (322.0 per 1000, 99% CI [306.3-338.1]). The most common pathogens were coagulase negative staphylococci (29.3%) and Staphylococcus aureus (23.0%), but 34 different pathogens were identified. Infected infants had lower survival (adjusted risk ratio [aRR] 0.89, 95% CI [0.87-0.90]) and increased risks of home oxygen (aRR 1.32, 95% CI [1.26-1.38]), tracheostomy (aRR 2.88, 95% CI [2.47-3.37]), and gastrostomy (aRR 2.09, 95% CI [1.93-2.57]) among survivors.

CONCLUSIONS: A substantial proportion of very preterm infants continue to suffer late-onset sepsis, particularly those born at the lowest GAs. Infected infants had higher mortality, and survivors had increased risks of technology-dependent chronic morbidities. The persistent burden and diverse microbiology of late-onset sepsis among very preterm infants underscore the need for innovative and potentially organism-specific prevention strategies.

OBJECTIVE: To determine the time to positivity (TTP) of blood cultures among infants with late-onset bacteraemia and predictors of TTP >36 hours.

DESIGN: Retrospective cohort study.

SETTING: 16 birth centres in two healthcare systems.

PATIENTS: Infants with positive blood cultures obtained >72 hours after birth.

OUTCOME: The main outcome was TTP, defined as the time interval from specimen collection to when a neonatal provider was notified of culture growth. TTP analysis was restricted to the first positive culture per infant. Patient-specific and infection-specific factors were analysed for association with TTP >36 hours.

RESULTS: Of 10 235 blood cultures obtained from 3808 infants, 1082 (10.6%) were positive. Restricting to bacterial pathogens and the first positive culture, the median TTP (25th-75th percentile) for 428 cultures was 23.5 hours (18.4-29.9); 364 (85.0%) resulted in 36 hours. Excluding coagulase-negative staphylococci (CoNS), 275 of 294 (93.5%) cultures were flagged positive by 36 hours. In a multivariable model, CoNS isolation and antibiotic pretreatment were significantly associated with increased odds of TTP >36 hours. Projecting a 36-hour empiric duration at one site and assuming that all negative evaluations were associated with an empiric course of antibiotics, we estimated that 1164 doses of antibiotics would be avoided in 629 infants over 10 years, while delaying a subsequent antibiotic dose in 13 infants with bacteraemia.

CONCLUSIONS: Empiric antibiotic administration in late-onset infection evaluations (not targeting CoNS) can be stopped at 36 hours. Longer durations (48 hours) should be considered when there is pretreatment or antibiotic therapy is directed at CoNS.

<p><strong>OBJECTIVE: </strong>To determine the time to positivity (TTP) of blood cultures among infants with late-onset bacteraemia and predictors of TTP &gt;36 hours.</p>

<p><strong>DESIGN: </strong>Retrospective cohort study.</p>

<p><strong>SETTING: </strong>16 birth centres in two healthcare systems.</p>

<p><strong>PATIENTS: </strong>Infants with positive blood cultures obtained &gt;72 hours after birth.</p>

<p><strong>OUTCOME: </strong>The main outcome was TTP, defined as the time interval from specimen collection to when a neonatal provider was notified of culture growth. TTP analysis was restricted to the first positive culture per infant. Patient-specific and infection-specific factors were analysed for association with TTP &gt;36 hours.</p>

<p><strong>RESULTS: </strong>Of 10 235 blood cultures obtained from 3808 infants, 1082 (10.6%) were positive. Restricting to bacterial pathogens and the first positive culture, the median TTP (25th-75th percentile) for 428 cultures was 23.5 hours (18.4-29.9); 364 (85.0%) resulted in 36 hours. Excluding coagulase-negative staphylococci (CoNS), 275 of 294 (93.5%) cultures were flagged positive by 36 hours. In a multivariable model, CoNS isolation and antibiotic pretreatment were significantly associated with increased odds of TTP &gt;36 hours. Projecting a 36-hour empiric duration at one site and assuming that all negative evaluations were associated with an empiric course of antibiotics, we estimated that 1164 doses of antibiotics would be avoided in 629 infants over 10 years, while delaying a subsequent antibiotic dose in 13 infants with bacteraemia.</p>

<p><strong>CONCLUSIONS: </strong>Empiric antibiotic administration in late-onset infection evaluations (not targeting CoNS) can be stopped at 36 hours. Longer durations (48 hours) should be considered when there is pretreatment or antibiotic therapy is directed at CoNS.</p>

<p><strong>OBJECTIVES: </strong>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.</p>

<p><strong>STUDY DESIGN: </strong>Retrospective, matched cohort study in a single-center level IV NICU. 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. Non-exposed infants ("controls") were matched 1:1 to exposed infants based on gestational and corrected gestational age, and had negative sepsis evaluations with antibiotic durations &lt;48 hours. AKI was defined by modified neonatal Kidney Disease Improving Global Outcomes criteria. Statistical analysis included Mann-Whitney and Chi-square tests, multivariable logistic regression, and Kaplan-Meier time-to-event analysis.</p>

<p><strong>RESULTS: </strong>Among 203 episodes of late-onset sepsis, 40 (20%) developed AKI within 7 days following evaluation, and among 193 episodes with negative cultures, 16 (8%) resulted in AKI (p=0.001). Episodes of sepsis also led to greater AKI severity, compared with non-septic 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=0.002). AKI was associated with increased 30-day mortality (aOR 4.5, 95% CI 1.3-15.6, p=0.017).</p>

<p><strong>CONCLUSIONS: </strong>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.</p>