Coming Into Resistance: Clinically Important Antibiotic Resistance Genes in NICU vs. Healthy Infants
- 1Clinical Microbiome Unit, Laboratory of Host Immunity and Microbiome, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Na
Abstract
ImportanceAntibiotic-resistant infections in neonates often arise from the infants own colonizing bacteria harboring antibiotic resistance genes (ARG). This study evaluates ARG that impact antibiotic selection and drive resistance-related mortality, termed clinically important antibiotic resistance genes (CI-ARG).
ObjectiveTo determine differences in gut CI-ARG abundance in children from birth through 3 years old, stratified by neonatal intensive care unit (NICU) admission and antibiotic (abx) exposure in the first two months
DesignCohort study (sequencing, analysis completed 2025-2026) using shotgun metagenomic sequencing of stool samples from infants in two studies: "Neonatal Intestinal Microbiome" (+NICU groups, 2015-2022), "The First 1000 Days of Life and Beyond" (-NICU groups, 2018-2021). Infants grouped into four cohorts: +NICU/+abx, +NICU/-abx, -NICU/-abx, and -NICU/+abx. Prespecified CI-ARG abundance compared longitudinally among groups.
SettingNICU, well-baby nursery, Inova Fairfax Hospital, Virginia
Participants+NICU criteria: admission to the NICU, anticipated length of stay (LOS) of at least five days, maternal age [≥]18 years. -NICU: parents with good general health and age [≥]18 years enrolled prior to infant birth. Stool samples: adequate stool processing volume, at least one stool sample from before one month and after one year of age, 7-day minimum between serial samples.
ExposuresNICU versus well-baby nursery; antibiotics versus none in first two months of corrected age
Main Outcomes and MeasuresPredefined primary outcome-longitudinal CI-ARG abundance by group, compared using linear mixed effects models with adjustment for multiple comparisons (Benjamini-Hochberg procedure). Predefined secondary outcomes-differences in overall microbiota and resistome composition.
Results1000 serial stool samples, 179 infants (birth-39 months). Longitudinal abundance significantly differed among cohorts for 11 CI-ARG (p<0.05); often higher in the +NICU groups in early life, with or without antibiotic exposure. Abundance of ARG conferring resistance to aminoglycosides, macrolides, and fluoroquinolones later decreased below -NICU levels. mecA, which often drives methicillin resistance in Staphylococcus, was detected only in +NICU infants during premature period.
ConclusionsThis longitudinal study demonstrates significant longitudinal CI-ARG differences in children grouped by early-life NICU status and/or antibiotic exposure. Future studies should explore the mechanisms driving these CI-ARG changes and evaluate their impact on infection risk and community spread.
Key PointsO_ST_ABSQuestionC_ST_ABSHow do clinically important antibiotic resistance genes (CI-ARG) differ longitudinally among infants up to 3 years old based on NICU admission and antibiotic exposure in the first two months of life?
FindingsIn this cohort study of 179 infants through 39 months of age, longitudinal abundance was significantly different for 11 prespecified CI-ARG, often higher in the NICU groups in early life, with or without antibiotic exposure.
MeaningChildren with a history of NICU hospitalization, whether due to the NICU environment itself, prematurity, or other factors, may have increased CI-ARG burden early in life, irrespective of direct antibiotic exposure.
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BibTeX
@misc{strength2026coming,
title = {{Coming Into Resistance: Clinically Important Antibiotic Resistance Genes in NICU vs. Healthy Infants}},
author = {R. E. Strength and A. Angelova and E. Robbins and S. Levy and K. E. McCauley and K. M. Lloyd and E. B. Margolis and A. S. Burns and S. Mistry and P. Subramanian and A. Dassner and C. Zerbe and V. I. Band and S. Namasivayam and Q. Chen and E. Esadah and K. Rees and M. Bacorn and R. Prasad and P. LaPoint and H. N. Romero-Soto and J. P. Dekker and C. L. Sears and C. Shapiro and R. F. Hamdy and J. M. Campos and S. K. Hourigan},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.23.26363796},
url = {https://www.medrxiv.org/content/10.64898/2026.09.23.26363796v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Coming Into Resistance: Clinically Important Antibiotic Resistance Genes in NICU vs. Healthy Infants
AU - R. E. Strength
AU - A. Angelova
AU - E. Robbins
AU - S. Levy
AU - K. E. McCauley
AU - K. M. Lloyd
AU - E. B. Margolis
AU - A. S. Burns
AU - S. Mistry
AU - P. Subramanian
AU - A. Dassner
AU - C. Zerbe
AU - V. I. Band
AU - S. Namasivayam
AU - Q. Chen
AU - E. Esadah
AU - K. Rees
AU - M. Bacorn
AU - R. Prasad
AU - P. LaPoint
AU - H. N. Romero-Soto
AU - J. P. Dekker
AU - C. L. Sears
AU - C. Shapiro
AU - R. F. Hamdy
AU - J. M. Campos
AU - S. K. Hourigan
PY - 2026
DA - 2026/09/23
PB - medRxiv
DO - 10.64898/2026.09.23.26363796
UR - https://www.medrxiv.org/content/10.64898/2026.09.23.26363796v1
AB - ImportanceAntibiotic-resistant infections in neonates often arise from the infants own colonizing bacteria harboring antibiotic resistance genes (ARG). This study evaluates ARG that impact antibiotic selection and drive resistance-related mortality, termed clinically important antibiotic resistance genes (CI-ARG). ObjectiveTo determine differences in gut CI-ARG abundance in children from birth through 3 years old, stratified by neonatal intensive care unit (NICU) admission and antibiotic (abx) exposure in the first two months DesignCohort study (sequencing, analysis completed 2025-2026) using shotgun metagenomic sequencing of stool samples from infants in two studies: "Neonatal Intestinal Microbiome" (+NICU groups, 2015-2022), "The First 1000 Days of Life and Beyond" (-NICU groups, 2018-2021). Infants grouped into four cohorts: +NICU/+abx, +NICU/-abx, -NICU/-abx, and -NICU/+abx. Prespecified CI-ARG abundance compared longitudinally among groups. SettingNICU, well-baby nursery, Inova Fairfax Hospital, Virginia Participants+NICU criteria: admission to the NICU, anticipated length of stay (LOS) of at least five days, maternal age [≥]18 years. -NICU: parents with good general health and age [≥]18 years enrolled prior to infant birth. Stool samples: adequate stool processing volume, at least one stool sample from before one month and after one year of age, 7-day minimum between serial samples. ExposuresNICU versus well-baby nursery; antibiotics versus none in first two months of corrected age Main Outcomes and MeasuresPredefined primary outcome-longitudinal CI-ARG abundance by group, compared using linear mixed effects models with adjustment for multiple comparisons (Benjamini-Hochberg procedure). Predefined secondary outcomes-differences in overall microbiota and resistome composition. Results1000 serial stool samples, 179 infants (birth-39 months). Longitudinal abundance significantly differed among cohorts for 11 CI-ARG (p<0.05); often higher in the +NICU groups in early life, with or without antibiotic exposure. Abundance of ARG conferring resistance to aminoglycosides, macrolides, and fluoroquinolones later decreased below -NICU levels. mecA, which often drives methicillin resistance in Staphylococcus, was detected only in +NICU infants during premature period. ConclusionsThis longitudinal study demonstrates significant longitudinal CI-ARG differences in children grouped by early-life NICU status and/or antibiotic exposure. Future studies should explore the mechanisms driving these CI-ARG changes and evaluate their impact on infection risk and community spread. Key PointsO_ST_ABSQuestionC_ST_ABSHow do clinically important antibiotic resistance genes (CI-ARG) differ longitudinally among infants up to 3 years old based on NICU admission and antibiotic exposure in the first two months of life? FindingsIn this cohort study of 179 infants through 39 months of age, longitudinal abundance was significantly different for 11 prespecified CI-ARG, often higher in the NICU groups in early life, with or without antibiotic exposure. MeaningChildren with a history of NICU hospitalization, whether due to the NICU environment itself, prematurity, or other factors, may have increased CI-ARG burden early in life, irrespective of direct antibiotic exposure.
ER -