Author: Lucy Carpenter
Carpenter, Lucy, 2023 Characterising the unintended consequences of antibiotic use on the microbiome and resistome: a metagenomic approach, Flinders University, College of Medicine and Public Health
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Antibiotics are an essential component of contemporary healthcare but their increasing use has accelerated the rate of antibiotic resistance. Currently, data on multidrug resistant organisms (MDROs) comes from diagnostic sources such as during infection and from sources that use only culture-based techniques. However, the consequences of antibiotic use such as carriage and transmission of antibiotic resistance genes in organisms asymptomatically, as well as disruption of the protective commensal microbiome, are rarely considered. Children and elderly people who typically exhibit microbiome instability and less robust immune responses are at high risk of poor clinical outcomes when the effectiveness of antibiotic treatment is reduced. One way to better understand changes in the microbiome and resistome is the application of sequencing-based approaches. This project aimed to use such approaches in two clinical cohorts to characterise the unintended consequences of antibiotics on the gut microbiome and resistome. The first cohort, the Cellulitis at Home or Inpatient in Children presenting to the Emergency department (CHOICE) study, was a randomised control trial (RCT) that compared the efficacy and safety of inpatient intravenous (IV) flucloxacillin with outpatient IV ceftriaxone in children who presented to emergency with cellulitis. The second, the Generating evidence on Resistant bacteria in the Aged Care Environment (GRACE) study, was an observational study that investigated the impact of the residential aged care environment on the gut resistome. In both studies, sequencing-based approaches were applied to investigate how a single, controlled antibiotic exposure (CHOICE) and a multi, uncontrolled antibiotic exposure pattern (GRACE) impacted the microbiome and resistome. Responses in the gut microbiome and resistome differed substantially in each cohort. In children treated with antibiotics for cellulitis, no changes to the resistome, or carriage of genes known to be associated with broad-spectrum beta-lactam use were found. Although the microbiome was affected, this only occurred transiently and protective commensal bacteria increased in abundance shortly after treatment ceased. In a cohort of elderly, institutionalised people, the abundance of genes conferring antibiotic resistance were much higher in those who had recent and frequent antibiotic exposure compared to those who had no exposure. Microbiome richness was also much lower in these people, owing to the characteristics of the microbiome previously observed in the elderly and those in aged-care facilities. Antibiotic use has a significant impact on the gut resistome and microbiome in both young children and residents of aged-care facilities. The findings reported in this thesis indicate that the use of metagenomic sequencing should be more frequently adopted in medical decision-making, particularly in the development of antibiotic stewardship policies, where the impact of asymptomatic carriage of resistance genes and microbiome disruption is often not considered.
Keywords: microbiome, resistome, antibiotic resistance, aged care, hospital, antibiotics
Subject: Microbiology & Infectious Diseases thesis
Thesis type: Doctor of Philosophy
Completed: 2023
School: College of Medicine and Public Health
Supervisor: Geraint Rogers