Ohio Statewide Quality-Improvement Collaborative to Reduce Late-Onset Sepsis in Preterm Infants

BACKGROUND: Early empiric antibiotic exposure appears to negatively influence feeding tolerance in preterm infants. However, the effect of prolonged antibiotic treatment is unknown. The objective of this study was to investigate whether prolonged antibiotics impact the time to full enteral feed in infants less than 29 weeks of gestational age with negative blood cultures. METHODS: Retrospective data for infants less than 29 weeks gestation age were retrieved from the PEARL-Peristat perinatal registry in Qatar. Exclusion criteria were major congenital anomalies, conditions requiring surgery in the first 10 days of life, positive blood cultures in the first 48 hours of life, and death within the first week of life. Antibiotic courses were categorized as prolonged if continued more than 48 hours. The primary outcome was the duration of total parenteral nutrition. RESULTS: Of 199 study infants, 185 (92.9%) underwent antibiotic treatment for > 48 hours despite negative blood cultures. The median duration of parenteral nutrition was not significantly different between the prolonged and short antibiotic groups (25 and 22 days, respectively; p = 0.139). Infants with prolonged antibiotic courses experienced non-significantly higher levels of necrotizing enterocolitis (7.1% and 18.4%, respectively), bronchopulmonary dysplasia (28.6% and 45.4%, respectively), and retinopathy of prematurity (14.3% and 38.4%, respectively). There were no differences in the late-onset sepsis rate (78.6% and 82.1%, respectively) and the in-hospital death rate (7.1% and 7.6%, respectively). CONCLUSIONS: Prolonged antibiotic treatment in infants less than 29 weeks gestation with negative blood cultures has no significant impact on the time to full enteral feed.

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ELFIN, the United Kingdom preterm lactoferrin trial: interpretation and future questions

Biochemistry and Cell Biology ◽

10.1139/bcb-2020-0073 ◽

2020 ◽

Author(s):

Janet Elizabeth Berrington ◽

William McGuire ◽

NIcholas David Embleton

Keyword(s):

United Kingdom ◽

Preterm Infants ◽

Late Onset ◽

Disease Onset ◽

Intervention Group ◽

Control Group ◽

Bovine Lactoferrin ◽

The United Kingdom ◽

Late Onset Sepsis ◽

The Uk

Previous studies suggested that supplemental bovine lactoferrin (BLF) given to preterm infants (<32 weeks gestation) may reduce late onset sepsis (LOS) and necrotising enterocolitis (NEC), but have been underpowered. The Enteral Lactoferrin in Neonates (ELFIN) study, performed in the United Kingdom (UK), aimed to further address this issue with a well powered double blinded placebo controlled trial of >2200 preterm infants. ELFIN did not demonstrate a reduction in LOS or NEC, or several other clinically important measures. 316 (29%) of 1093 infants in the intervention group developed late-onset sepsis versus 334 (31%) of 1089 in the control group with an adjusted risk ratio of 0·95 (95% CI 0·86–1·04; p=0· 233). Reasons for the differences in ELFIN trial results and other studies may include population differences, the routine use of antifungals in the UK, timing of administration of the lactoferrin in relation to disease onset, or specific properties of the lactoferrin used in different trials. Further exploration is being undertaken in the UK NIHR funded Mechanisms Affecting the Guts of Preterm Infants in Enteral feeding trials (MAGPIE) study, for which results should be available soon.

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Late-Onset Sepsis in Very Low Birth Weight Preterm Infants: 7 years’ Experience at a Tertiary Hospital in China

Pediatrics & Neonatology ◽

10.1016/j.pedneo.2021.05.011 ◽

2021 ◽

Author(s):

Liya Ma ◽

Qiongling Peng ◽

Wei Wang ◽

Yi Yang ◽

You Chen ◽

...

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Preterm Infants ◽

Very Low Birth Weight ◽

Late Onset ◽

Tertiary Hospital ◽

Late Onset Sepsis

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Cause of preterm birth and late-onset sepsis in very preterm infants: the EPIPAGE-2 cohort study

Pediatric Research ◽

10.1038/s41390-021-01411-y ◽

2021 ◽

Author(s):

Mathilde Letouzey ◽

◽

Laurence Foix-L’Hélias ◽

Héloïse Torchin ◽

Ayoub Mitha ◽

...

Keyword(s):

Cohort Study ◽

Preterm Birth ◽

Preterm Infants ◽

Late Onset ◽

Very Preterm Infants ◽

Very Preterm ◽

Late Onset Sepsis

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Impaired Cytokine Responses to Live Staphylococcus epidermidis in Preterm Infants Precede Gram-positive, Late-onset Sepsis

Clinical Infectious Diseases ◽

10.1093/cid/ciaa063 ◽

2020 ◽

Author(s):

Tobias Strunk ◽

Julie Hibbert ◽

Dorota Doherty ◽

Elizabeth Nathan ◽

Karen Simmer ◽

...

Keyword(s):

Preterm Infants ◽

Staphylococcus Epidermidis ◽

Late Onset ◽

Gram Positive ◽

Cytokine Responses ◽

Inflammatory Protein ◽

Late Onset Sepsis ◽

Immunological Mechanisms ◽

Factor Α

Abstract Background Late-onset sepsis (LOS) with Staphylococcus epidermidis is common in preterm infants, but the immunological mechanisms underlying heightened susceptibility are poorly understood. Our aim is to characterize the ontogeny of cytokine responses to live S. epidermidis in preterm infants with and without subsequent Gram-positive LOS. Methods We conducted a prospective, observational cohort study of preterm infants (<30 weeks gestational age [GA]) with blood sampling on Days 1, 7, 14, 21, and 28 of life. Cytokine responses in peripheral whole blood stimulated with live S. epidermidis were analyzed by 11-plex immunoassay. Results Of 129 infants (mean GA, 26.2 weeks; mean birth weight, 887g), 23 (17.8%) had confirmed LOS with Gram-positive organisms and 15 (11.6%) had clinical sepsis, with median onsets at 13 and 15 days, respectively. Blood cytokine responses to an in vitro S. epidermidis challenge were similar between infected and uninfected infants on Day 1, but diverged thereafter. Infants with subsequent LOS displayed broadly reduced S. epidermidis–induced responses from Day 7 onwards, compared to those who did not develop LOS. This pattern was observed with chemokines (interleukin [IL]-8, monocyte chemotactic protein–1, and macrophage inflammatory protein–1α), pro-inflammatory cytokines (IL-1, IL-6, and tumor necrosis factor–α) and the regulatory cytokine IL-10. Conclusions Cytokine responses to a live S. epidermidis challenge are impaired in infants with LOS and precede the onset of clinical illness. Quantifying pathogen-specific cytokine responses at Day 7 may identify those high-risk preterm infants at the greatest risk of LOS, and prospective replication is warranted.

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