Clinical trial NCT02784821: Antibiotic "Dysbiosis" in Preterm Infants
Official title: Antibiotic Effects on the Developing Microbiome, Metabolome and Morbidities in Preterm Neonates
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Enterocolitis, Necrotizing
Bacteremia
Bronchopulmonary Dysplasia
Intraventricular Hemorrhage
Periventricular Leukomalacia
Chronic Lung Disease
Ileal Perforation
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Society for Pediatric Dermatology
First posted: 2016-05-27
Enrollment: 98
Sex: ALL
Minimum age (years): 23
Maximum age (years): 33
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* All infants less than 33 weeks gestation.

Exclusion Criteria:

* Infants who are non-viable at birth.

Primary outcomes:
measure: Number of Events of Composite Morbidities and Mortality, Including Necrotizing Enterocolitis (NEC), Late Onset Sepsis (LOS), Bronchopulmonary Dysplasia (BPD) and Death
timeFrame: Until discharge from the NICU, up to 1 year
Secondary outcomes:
measure: Number of Participants With Late Onset Sepsis
timeFrame: Until discharge from the NICU, up to 1 year
measure: Number of Participants With Bronchopulmonary Dysplasia (BPD)
timeFrame: Until discharge from the NICU, up to 1 year
measure: Number of Participants With Necrotizing Enterocolitis (NEC)
timeFrame: Until discharge from the NICU, up to 1 year
measure: Number of Deaths
timeFrame: until discharge from the NICU, up to one year.
measure: Length of Stay.
timeFrame: Average days +/- standard deviation of hospitalization, up to 15 weeks
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Josef Neu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.