Gastrointestinal Microbiome Disruption and Antibiotic-Associated Diarrhea in Children Receiving Antibiotic Therapy for Community-Acquired Pneumonia

Jiye Kwon; Yong Kong; Martina Wade; Derek J Williams; Clarence Buddy Creech; Scott Evans; Emmanuel B Walter; Judy M Martin; Jeffrey S Gerber; Jason G Newland; Meghan E Hofto; Mary Allen Staat; Henry F Chambers; Vance G Fowler; W Charles Huskins; Melinda M Pettigrew

doi:10.1093/infdis/jiac082

Gastrointestinal Microbiome Disruption and Antibiotic-Associated Diarrhea in Children Receiving Antibiotic Therapy for Community-Acquired Pneumonia

J Infect Dis. 2022 Sep 21;226(6):1109-1119. doi: 10.1093/infdis/jiac082.

Authors

Jiye Kwon¹, Yong Kong^{2

3}, Martina Wade¹, Derek J Williams⁴, Clarence Buddy Creech⁴, Scott Evans⁵, Emmanuel B Walter⁶, Judy M Martin⁷, Jeffrey S Gerber⁸, Jason G Newland⁹, Meghan E Hofto¹⁰, Mary Allen Staat¹¹, Henry F Chambers¹², Vance G Fowler¹³, W Charles Huskins¹⁴, Melinda M Pettigrew¹

Affiliations

¹ Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA.
² Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA.
³ Department of Molecular Biophysics and Biochemistry, W. M. Keck Foundation Biotechnology Resource Laboratory, Yale School of Medicine, New Haven, Connecticut, USA.
⁴ Department of Pediatrics and the Vanderbilt Vaccine Research Program, Vanderbilt University School of Medicine and the Monroe Carell Jr Children's Hospital at Vanderbilt, Nashville, Tennessee, USA.
⁵ Biostatistics Center, Milken Institute School of Public Health, George Washington University, Washington, District of Columbia, USA.
⁶ Department of Pediatrics and Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
⁷ Department of Pediatrics, University of Pittsburgh School of Medicine and the UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁸ Children's Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁹ Department of Pediatrics, Washington University in St Louis School of Medicine, St Louis, Missouri, USA.
¹⁰ Department of Pediatrics, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.
¹¹ Cincinnati Children's Hospital Medical Center; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
¹² Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
¹³ Department of Medicine and Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
¹⁴ Mayo Clinic College of Medicine and Science and Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Abstract

Antibiotic-associated diarrhea (AAD) is a common side effect of antibiotics. We examined the gastrointestinal microbiota in children treated with β-lactams for community-acquired pneumonia. Data were from 66 children (n = 198 samples), aged 6-71 months, enrolled in the SCOUT-CAP trial (NCT02891915). AAD was defined as ≥1 day of diarrhea. Stool samples were collected on study days 1, 6-10, and 19-25. Samples were analyzed using 16S ribosomal RNA gene sequencing to identify associations between patient characteristics, microbiota characteristics, and AAD (yes/no). Nineteen (29%) children developed AAD. Microbiota compositional profiles differed between AAD groups (permutational multivariate analysis of variance, P < .03) and across visits (P < .001). Children with higher baseline relative abundances of 2 Bacteroides species were less likely to experience AAD. Higher baseline abundance of Lachnospiraceae and amino acid biosynthesis pathways were associated with AAD. Children in the AAD group experienced prolonged dysbiosis (P < .05). Specific gastrointestinal microbiota profiles are associated with AAD in children.

Keywords: antibiotic-associated diarrhea; children; community-acquired pneumonia; microbiota.

Publication types

Clinical Trial
Research Support, N.I.H., Extramural

MeSH terms

Anti-Bacterial Agents* / adverse effects
Child, Preschool
Community-Acquired Infections* / drug therapy
Diarrhea* / chemically induced
Diarrhea* / drug therapy
Gastrointestinal Microbiome* / drug effects
Humans
Infant
Pneumonia* / drug therapy
beta-Lactams / therapeutic use

Substances

Anti-Bacterial Agents
beta-Lactams

Abstract

Publication types

MeSH terms

Substances

Grants and funding