Antibiotic "Dysbiosis" in Preterm Infants

NCT02784821 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB201501045-NR21HD088005
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

Prolonged antibiotic use in preterm neonates has significant consequences on the developing intestinal microbiome, metabolome and host response, predisposing the neonate to various major morbidities, including necrotizing enterocolitis (NEC), late-onset sepsis, bronchopulmonary dysplasia (BPD), and mortality. The hypothesis is that early and prolonged antibiotic use in preterm neonates has significant consequences on the developing intestinal microbiome, metabolome and host response, predisposing the neonate to various major morbidities. It is possible that the effect of this widespread antibiotic use outweighs the potential benefits. This study will randomize preterm infants born at less than 33 weeks gestation to either pre-emptive antibiotics or no-pre-emptive antibiotics. The purpose of this research is to evaluate the risks and benefits of current practice to determine optimal levels of antibiotic use that protects the babies from infection with minimal effect on the microbiome and subsequent adverse outcomes related to overuse of antibiotics.

Conditions

Enterocolitis, Necrotizing; Bacteremia; Bronchopulmonary Dysplasia; Intraventricular Hemorrhage; Periventricular Leukomalacia; Chronic Lung Disease; Ileal Perforation

Outcome Measures

Primary Outcomes (1)

• Number of Events of Composite Morbidities and Mortality, Including Necrotizing Enterocolitis (NEC), Late Onset Sepsis (LOS), Bronchopulmonary Dysplasia (BPD) and Death

  Enrolled subjects' medical record will be reviewed to determine the number of patients with the composite outcome and the association between antibiotic administration and the components of the composite outcome

  Until discharge from the NICU, up to 1 year

Secondary Outcomes (5)

• Number of Participants With Late Onset Sepsis

  Until discharge from the NICU, up to 1 year

• Number of Participants With Bronchopulmonary Dysplasia (BPD)

  Until discharge from the NICU, up to 1 year

• Number of Participants With Necrotizing Enterocolitis (NEC)

  Until discharge from the NICU, up to 1 year

• Number of Deaths

  until discharge from the NICU, up to one year.

• Length of Stay.

  Average days +/- standard deviation of hospitalization, up to 15 weeks

Study Arms (4)

Group A - Antibiotics Indicated

OTHER

These neonates have a clinical indication to receive antibiotics such as symptoms out of expected for gestation OR delivered to moms with high perinatal infectious risks. The standard of care antibiotics include Ampicillin and Gentamicin or Cefotaxime. Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.

Drug: Antibiotic; Other: Gastric fluid; Other: Breast milk; Other: Stool samples

Group B - antibiotics not indicated

OTHER

These neonates are asymptomatic AND are delivered to moms with low perinatal infectious risk factors. Antibiotics is not indicated for this group as standard of care. Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.

Other: Gastric fluid; Other: Breast milk; Other: Stool samples

Group CI/randomized to antibiotics

OTHER

This group will be randomized to receive standard of care antibiotics which include Ampicillin and Gentamicin or Cefotaxime. Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.

Other: Gastric fluid; Other: Breast milk; Other: Stool samples; Drug: Antibiotics

Group CII/randomized to no antibiotics

OTHER

This group will be randomized not to receive standard of care antibiotics. Study interventions will include the collection of samples for the following: breast milk, gastric fluid and stool samples for analysis of the microbiome.

Other: Gastric fluid; Other: Breast milk; Other: Stool samples

Interventions

Antibiotic DRUG

Babies that are assigned to antibiotics receive therapy based on the clinical team's discretion.

Also known as: Ampicillin or Gentamicin or Cefotaxime

Group A - Antibiotics Indicated

Gastric fluid OTHER

Microbiome evaluated using gastric aspirate.

Also known as: Gastric aspirate

Group A - Antibiotics Indicated; Group B - antibiotics not indicated; Group CI/randomized to antibiotics; Group CII/randomized to no antibiotics

Breast milk OTHER

Microbiome will be evaluated using mother's breast milk.

Group A - Antibiotics Indicated; Group B - antibiotics not indicated; Group CI/randomized to antibiotics; Group CII/randomized to no antibiotics

Stool samples OTHER

Microbiome will be evaluated using infant's stool.

Group A - Antibiotics Indicated; Group B - antibiotics not indicated; Group CI/randomized to antibiotics; Group CII/randomized to no antibiotics

Antibiotics DRUG

Babies that are randomized to antibiotics receive therapy based on the clinical team's discretion.

Also known as: Ampicillin or Gentamicin or Cefotaxime

Group CI/randomized to antibiotics

Eligibility Criteria

• Age: 23 Weeks - 33 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• All infants less than 33 weeks gestation.

You may not qualify if:

• Infants who are non-viable at birth.

Sponsors & Collaborators

• University of Florida: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Society for Pediatric Dermatology: collaborator

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

Related Publications (3)

• Ojeda A, Akinsuyi O, McKinley KL, Xhumari J, Triplett EW, Neu J, Roesch LFW. Increased antibiotic resistance in preterm neonates under early antibiotic use. mSphere. 2024 Oct 29;9(10):e0028624. doi: 10.1128/msphere.00286-24. Epub 2024 Oct 7.

  PMID: 39373498 DERIVED

• Singh NK, Will L, Al-Mulaabed S, Ruoss L, Li N, de La Cruz D, Gurka M, Neu J. Antibiotics Use and Its Effects on the Establishment of Feeding Tolerance in Preterm Neonates. Am J Perinatol. 2024 May;41(S 01):e2248-e2253. doi: 10.1055/a-2108-1960. Epub 2023 Jun 12.

  PMID: 37308133 DERIVED

• Russell JT, Lauren Ruoss J, de la Cruz D, Li N, Bazacliu C, Patton L, McKinley KL, Garrett TJ, Polin RA, Triplett EW, Neu J. Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants. Sci Rep. 2021 Jan 21;11(1):1943. doi: 10.1038/s41598-021-80982-6.

  PMID: 33479274 DERIVED

MeSH Terms

Conditions

Enterocolitis, Necrotizing; Bacteremia; Bronchopulmonary Dysplasia; Leukomalacia, Periventricular

Interventions

Anti-Bacterial Agents; Ampicillin; Gentamicins; Cefotaxime; Milk, Human

Condition Hierarchy (Ancestors)

Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Encephalomalacia; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cephacetrile; Cephalosporins; Thiazines; Milk; Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Dairy Products; Food; Food and Beverages

Limitations and Caveats

Limitations of our study are a small n, infants enrolled at the peri-viable and high risk gestation (high risk for mortality and serious adverse events), and high number of infants changed from group CII/no antibiotics to receive antibiotics in the first 48hours of life.

Results Point of Contact

• Title: Dr. Josef Neu
• Organization: University of Florida

neuj@peds.ufl.edu

352-733-0111

Study Officials

• Josef Neu, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2016
• First Posted: May 27, 2016
• Study Start: January 16, 2017
• Primary Completion: September 11, 2019
• Study Completion: September 11, 2019
• Last Updated: June 5, 2024
• Results First Posted: June 5, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)