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Completed

NCT Number: NCT02784821

Antibiotic "Dysbiosis" in Preterm Infants

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.

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Key information

Conditions

Enterocolitis, Necrotizing Bacteremia Bacterial Infections Bacterial Infections and Mycoses Brain Diseases Bronchopulmonary Dysplasia Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Chronic Lung Disease Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Encephalomalacia Enterocolitis Gastroenteritis Gastrointestinal Diseases Ileal Perforation Infant, Newborn, Diseases Infant, Premature, Diseases Infections Inflammation Intestinal Diseases Intraventricular Hemorrhage Leukomalacia, Periventricular Lung Diseases Lung Injury Nervous System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Periventricular Leukomalacia Respiratory Tract Diseases Sepsis Systemic Inflammatory Response Syndrome Vascular Diseases Ventilator-Induced Lung Injury

Age range

23 week–33 week

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Florida

Gainesville, Florida, 32610, United States

About this study

A majority of preterm very low birthweight (VLBW) infants are exposed to antibiotics. Surveys from large databases in the US show that the rate of culture proven bacteremia in these infants at birth is only between 1-2 percent.

Antibiotic use, especially when repeated, induces a perturbation ("dysbiosis") in gut microbiota that may not recover to the basal state. Antibiotic use increases the risk of subsequent disease and adverse outcomes. The dependence of the developing immune system on the intestinal microbiota is supported by emerging evidence from studies in animals demonstrating decreased resistance to subsequent disease with early exposure to antibiotics.

A retrospective review of 50,0261 neonates across 127 neonatal intensive care units (NICUs) from California showed a forty-fold variation in NICU antibiotic prescribing practice with similar burdens of proven infection and mortality. A large number of preterm infants are thus subjected to a potentially harmful course of antibiotics that provides no clear benefit. There remains a major gap in our understanding of antibiotic-related intestinal microbial dysbiosis and how this may result in disease.

There will be two aims. In the first aim, a prospective, randomized pilot study, will test the effects of pre-emptive postnatal antibiotics on the microbiome, metabolome and inflammatory responses in the neonate during the NICU course. The second aim will assess the effects of pre-emptive postnatal antibiotics on adverse outcomes in the neonate while in the NICU. The hypothesis is that higher antibiotic use will not be associated with decreased early onset sepsis and in fact, will be associated with increased adverse outcomes including retinopathy of prematurity, necrotizing enterocolitis, spontaneous ileal perforation, late onset sepsis, chronic lung disease, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, and mortality.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • All infants less than 33 weeks gestation.

Exclusion criteria

  • Infants who are non-viable at birth.

Treatment and study plan

Antibiotic

Drug

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

Other names: Ampicillin or Gentamicin or Cefotaxime

Gastric fluid

Other

Microbiome evaluated using gastric aspirate.

Other names: Gastric aspirate

breast milk

Other

Microbiome will be evaluated using mother's breast milk.

Stool samples

Other

Microbiome will be evaluated using infant's stool.

Antibiotics

Drug

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

Other names: Ampicillin or Gentamicin or Cefotaxime

Primary outcomes

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

    Time frame: Until discharge from the NICU, up to 1 year

    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

Secondary outcomes

  1. Number of Participants With Late Onset Sepsis

    Time frame: Until discharge from the NICU, up to 1 year

    Enrolled subjects' medical record will be reviewed to determine the number of patients who developed bacteremia after the first week of life (late onset sepsis) and the association between antibiotic administration and the development of late onset sepsis.

  2. Number of Participants With Bronchopulmonary Dysplasia (BPD)

    Time frame: Until discharge from the NICU, up to 1 year

    Enrolled subjects' medical record will be reviewed to determine the number of patients who developed BPD and the association between antibiotic administration and diagnosis of BPD.

  3. Number of Participants With Necrotizing Enterocolitis (NEC)

    Time frame: Until discharge from the NICU, up to 1 year

    Enrolled subjects' medical record will be reviewed to determine the number of patients who developed NEC and the association between antibiotic administration and necrotizing enterocolitis

  4. Number of Deaths

    Time frame: until discharge from the NICU, up to one year.

    Enrolled subjects' medical record will be reviewed to determine the number of death prior to discharge from neonatal intensive care unit

  5. Length of Stay.

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

    length of stay in NICU in days.

Sponsors and collaborators

Lead sponsor

University of Florida

Other

Collaborators

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • Society for Pediatric Dermatology

Registry information

Official study title

Antibiotic Effects on the Developing Microbiome, Metabolome and Morbidities in Preterm Neonates

Important dates

Study start
2017
Primary completion
2019
Study completion
2019
First posted
May 27, 2016
Registry last updated
Jun 5, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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