Neonatal Outcomes Following Culture-negative Late-onset Sepsis Among 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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Ohio Statewide Quality-Improvement Collaborative to Reduce Late-Onset Sepsis in Preterm Infants

PEDIATRICS ◽

10.1542/peds.2010-2141 ◽

2011 ◽

Vol 127 (3) ◽

pp. 427-435 ◽

Cited By ~ 81

Author(s):

H. C. Kaplan ◽

C. Lannon ◽

M. C. Walsh ◽

E. F. Donovan ◽

Keyword(s):

Quality Improvement ◽

Preterm Infants ◽

Late Onset ◽

Quality Improvement Collaborative ◽

Late Onset Sepsis

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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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Comparison of neonatal outcomes of small for gestational age and appropriate for gestational age preterm infants born at 28–36 weeks of gestation: a multicentre study in Ethiopia

BMJ Paediatrics Open ◽

10.1136/bmjpo-2020-000740 ◽

2020 ◽

Vol 4 (1) ◽

pp. e000740

Author(s):

Netsanet Workneh Gidi ◽

Robert L Goldenberg ◽

Assaye K Nigussie ◽

Elizabeth McClure ◽

Amha Mekasha ◽

...

Keyword(s):

Preterm Infants ◽

Gestational Age ◽

Small For Gestational Age ◽

Late Onset ◽

Early Recognition ◽

Neonatal Outcomes ◽

P Value ◽

Prolonged Hospitalisation ◽

Increased Risk ◽

Appropriate For Gestational Age

PurposeThe aim of this study was to assess morbidity and mortality pattern of small for gestational age (SGA) preterm infants in comparison to appropriate for gestational age (AGA) preterm infants of similar gestational age.MethodWe compared neonatal outcomes of 1336, 1:1 matched, singleton SGA and AGA preterm infants based on their gestational age using data from the study ‘Causes of Illness and Death of Preterm Infants in Ethiopia (SIP)’. Data were analysed using SPSS V.23. ORs and 95% CIs and χ2 tests were done, p value of <0.05 was considered statistically significant.ResultThe majority of the infants (1194, 89%) were moderate to late preterm (32–36 weeks of gestation), 763 (57%) were females. Male preterm infants had higher risk of being SGA than female infants (p<0.001). SGA infants had increased risk of hypoglycaemic (OR and 95% CI 1.6 (1.2 to 2.0), necrotising enterocolitis (NEC) 2.3 (1.2 to 4.1), polycythaemia 3.0 (1.6 to 5.4), late-onset neonatal sepsis (LOS) 3.6 (1.1 to 10.9)) and prolonged hospitalisation 2.9 (2.0 to 4.2). The rates of respiratory distress syndrome (RDS), apnoea and mortality were similar in the SGA and AGA groups.ConclusionNeonatal complications such as hypoglycaemic, NEC, LOS, polycythaemia and prolonged hospitalisation are more common in SGA infants, while rates of RDS and mortality are similar in SGA and AGA groups. Early recognition of SGA status, high index of suspicion and screening for complications associated and timely intervention to prevent complications need due consideration.

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Neurodevelopmental outcomes following neonatal late-onset sepsis and blood culture-negative conditions

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2020-320664 ◽

2021 ◽

pp. fetalneonatal-2020-320664

Author(s):

Sagori Mukhopadhyay ◽

Karen M Puopolo ◽

Nellie I Hansen ◽

Scott A Lorch ◽

Sara B DeMauro ◽

...

Keyword(s):

Blood Culture ◽

Late Onset ◽

Antibiotic Administration ◽

Adjusted Relative Risk ◽

Neurodevelopmental Outcomes ◽

Risk Of Death ◽

Late Onset Sepsis ◽

Early Onset Sepsis ◽

Culture Negative

ObjectiveDetermine risk of death or neurodevelopmental impairment (NDI) in infants with late-onset sepsis (LOS) versus late-onset, antibiotic-treated, blood culture-negative conditions (LOCNC).DesignRetrospective cohort study.Setting24 neonatal centres.PatientsInfants born 1/1/2006–31/12/2014, at 22–26 weeks gestation, with birth weight 401–1000 g and surviving >7 days were included. Infants with early-onset sepsis, necrotising enterocolitis, intestinal perforation or both LOS and LOCNC were excluded.ExposuresLOS and LOCNC were defined as antibiotic administration for ≥5 days with and without a positive blood/cerebrospinal fluid culture, respectively. Infants with these diagnoses were also compared with infants with neither condition.OutcomesDeath or NDI was assessed at 18–26 months corrected age follow-up. Modified Poisson regression models were used to estimate relative risks adjusting for covariates occurring ≤7 days of age.ResultsOf 7354 eligible infants, 3940 met inclusion criteria: 786 (20%) with LOS, 1601 (41%) with LOCNC and 1553 (39%) with neither. Infants with LOS had higher adjusted relative risk (95% CI) for death/NDI (1.14 (1.05 to 1.25)) and death before follow-up (1.71 (1.44 to 2.03)) than those with LOCNC. Among survivors, risk for NDI did not differ between the two groups (0.99 (0.86 to 1.13)) but was higher for LOCNC infants (1.17 (1.04 to 1.31)) compared with unaffected infants.ConclusionsInfants with LOS had higher risk of death, but not NDI, compared with infants with LOCNC. Surviving infants with LOCNC had higher risk of NDI compared with unaffected infants. Improving outcomes for infants with LOCNC requires study of the underlying conditions and the potential impact of antibiotic exposure.

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Dynamics of the Preterm Gut Microbiome in Health and Disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00399.2020 ◽

2021 ◽

Author(s):

Alain C Cuna ◽

Michael J Morowitz ◽

Ishfaq Ahmed ◽

Shahid Umar ◽

Venkatesh Sampath

Keyword(s):

Preterm Infants ◽

Gut Microbiome ◽

Recent Literature ◽

Late Onset ◽

Perinatal Period ◽

Future Directions ◽

Late Onset Sepsis ◽

Microbiome Research ◽

Life Threatening ◽

Health And Disease

Advances in metagenomics have allowed a detailed study of the gut microbiome, and its role in human health and disease. Infants born prematurely possess a fragile gut microbial ecosystem that is vulnerable to perturbation. Alterations in the developing gut microbiome in preterm infants are linked to life-threatening diseases such as necrotizing enterocolitis (NEC) and late onset sepsis; and may impact future risk of asthma, atopy, obesity, and psychosocial disease. In this mini review, we summarize recent literature on the origins and patterns of development of the preterm gut microbiome in the perinatal period. The host-microbiome-environmental factors that portend development of dysbiotic intestinal microbial patterns associated with NEC and sepsis are reviewed. Strategies to manipulate the microbiome and mitigate dysbiosis, including the use of probiotics and prebiotics will also be discussed. Finally, we explore the challenges and future directions of gut microbiome research in preterm infants.

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