Session : SHEA Decennial Top Oral Abstract Awards

208 - The Gut Microbiome and Resistome of Healthy Volunteers Are Restructured After Short Courses of Antibiotics

Oral Abstract

Location: On Demand

Background: Antimicrobial exposure is a significant risk factor for the development of antibiotic-resistant organisms (ARO); however, the depth and duration of this impact is not well described. The study goal is to define impact of antibiotics (ABX) on the gut microbiome of healthy volunteers (HV).

Methods: HV were randomized to receive either 5 days of levofloxacin (LVX), azithromycin (AZM), cefpodoxime (CPD), or AZM + CPD (Figure 1). Stool samples were collected at 15 time points per patient before, during, and after ABX. Remnant stool samples from the microbiology laboratory were collected from patients admitted to the medical intensive care unit (MICU) as a comparison of the microbiome in a critically ill state. DNA was extracted from samples, then underwent shotgun sequencing. Relative abundance, resistome, and metabolic pathway abundance of bacterial taxa were determined and statistical analysis conducted in R.

Results: 289 stool specimens from 20 HVs, and 26 remnant stool specimens were obtained from patients admitted from the MICU (Figure 1). Community diversity and richness decreased in the first week post-ABX for all HVs (p < 0 .01). Linear discriminant analysis identified Bacteroides and Clostridium as taxonomic groups enriched after CPD, while AZM and LVX produced a relative abundance increase in diverse Firmicutes spp. Longitudinal tracking confirmed that after all ABX except for LVX, HV microbiomes lose species diversity and shift towards a state similar to that of MICU patients (Figure 2). The gut microbiome of most HVs exhibited resiliency and returned to a higher diversity level similar to their starting point, however 10% of HVs did not. Moreover, there are ABX specific increases in resistance markers, revealing innate resistance to beta-lactams and macrolides within the gut microbiome of the HVs. Finally, HV microbiomes which shifted towards a MICU-like taxonomic state also clustered with microbial metabolic profiles from MICU patients. HVs microbial metabolic profiles were significantly enriched for important biosynthesis pathways producing chorismate and polysaccharides. MICU patients gut microbiomes were enriched for fatty acid regulation and quinolone biosynthesis, and for many degradation pathways important for different aspects of antibiotic resistance such as membrane integrity, alternative respiration, and antibiotic inactivation.

Conclusion: Short courses of antibiotics can cause acute and chronic microbiome disruptions in HVs, as evidenced by decreased microbiome diversity and increases in specific innate resistance elements. This data supports the need for antimicrobial stewardship to support rationale antibiotic use to prevent gut microbiome disruptions.

Co-Author(s)

WA

Winston Anthony

Disclosure: No Disclosure
KS

Kimberley Sukhum

Disclosure: No Disclosure
CC

Candice Cass, Associate in Arts

Clinical Research Study Ass. 2
Washington University
St. Louis, Missouri

Disclosure: No Disclosure
KR

Kimberly Reske, MPH

Research coordinator
Washington University
St. Louis, Missouri

Disclosure: No Disclosure
SS

Sondra Seiler, BA

Research Coordinator
Washington University
St. Louis, Missouri

Disclosure: No Disclosure
TH

Tiffany Hink, BS; MT, ASCP

Research Lab Supervisor
Washington University
St. Louis, Missouri

Disclosure: No Disclosure
CC

Christopher Coon

Disclosure: No Disclosure
AD

Alaric D'Souza

Disclosure: No Disclosure
BW

Bin Wang, MS

Research Technician
Washington University
St. Louis, Missouri

Disclosure: No Disclosure
ED

Erik R. Dubberke, MD, MSPH

Professor of Medicine
Washington University
St. Louis, Missouri

Disclosure: No Disclosure
Carey-Ann Burnham, PhD

Professor of Pathology & Immunology, Molecular Microbiology, Pediatrics, and Medicine
Washington University
St. Louis, Missouri

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
GD

Gautam Dantas, PhD

Professor
Washington University
St. Louis, Missouri

Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Presenting Author(s)

Jennie H. Kwon, DO;MS

Assistant Professor
Washington University - School of Medicine
St. Louis, Missouri

Disclosure: No Disclosure

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