medRxiv : the preprint server for health sciences · 2026
Coming Into Resistance: Clinically Important Antibiotic Resistance Genes in NICU vs. Healthy Infants.
СтатьяПрепринтНазвание и аннотация: Перевод пока не подготовлен
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Strength Rachel E, Angelova Angelina, Robbins Emily, Levy Shira, McCauley Kathryn E, Lloyd Kevin M, Margolis Elisa B, Burns Andrew S, Mistry Shreni, Subramanian Poorani, Dassner Aimee, Zerbe Christa, Band Victor I, Namasivayam Sivaranjani, Chen Qing, Esadah Esther, Rees Katherine, Bacorn Mickayla, Prasad Ruhika, LaPoint Phoebe, Romero-Soto Hector N, Dekker John P, Sears Cynthia L, Shapiro Craig, Hamdy Rana F, Campos Joseph M, Hourigan Suchitra K
Аннотация
IMPORTANCE: Antibiotic-resistant infections in neonates often arise from the infant's 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).
OBJECTIVE: To 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.
DESIGN: Cohort 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.
SETTING: NICU, 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.
EXPOSURES: NICU versus well-baby nursery; antibiotics versus none in first two months of corrected age.
MAIN OUTCOMES AND MEASURES: Predefined 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.
RESULTS: 1000 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.
CONCLUSIONS: This 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 POINTS: Question: How 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?Findings: In 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.Meaning: Children 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.
OBJECTIVE: To 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.
DESIGN: Cohort 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.
SETTING: NICU, 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.
EXPOSURES: NICU versus well-baby nursery; antibiotics versus none in first two months of corrected age.
MAIN OUTCOMES AND MEASURES: Predefined 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.
RESULTS: 1000 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.
CONCLUSIONS: This 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 POINTS: Question: How 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?Findings: In 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.Meaning: Children 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.