Unravelling the complex interplay between antibiotic consumption and adaptive changes in methicillin-resistant Staphylococcus aureus

Author:

van Hal Sebastiaan J123ORCID,Jensen Slade O34,Tong Stephen Y C56,Bentley Stephen7,Holden Matthew T8ORCID

Affiliation:

1. Department of Microbiology and Infectious Diseases, Royal Prince Alfred Hospital , Sydney , Australia

2. Sydney Medical School, Faculty of Medicine and Health, University of Sydney , Sydney , Australia

3. Antimicrobial Resistance and Mobile Elements Group, Ingham Institute for Applied Medical Research , Sydney, NSW , Australia

4. Microbiology and Infectious Diseases, School of Medicine, Western Sydney University , Sydney, NSW , Australia

5. Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity , Melbourne , Australia

6. Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne , Australia

7. Wellcome Sanger Institute, Wellcome Genome Campus , Hinxton, Cambridge CB10 1SA , UK

8. School of Medicine, University of St Andrews , St Andrews, Fife KY16 9TF , UK

Abstract

Abstract Objectives This study aims to elucidate the genomic dynamics driving the emergence of antimicrobial resistance (AMR), with a specific focus on the interplay between AMR and antimicrobial usage. Methods We conducted a comprehensive analysis using a ST239 methicillin-resistant Staphylococcus aureus (MRSA) dataset over a continuous 12-year period from a single hospital. Genomic analyses were performed tracking the changes in MRSA populations, particularly the emergence of reduced vancomycin susceptibility, and assessing the impact of glycopeptide use on these emergence events. Results Our findings reveal a significant correlation between hospital glycopeptide usage and the selection of MRSA strains with reduced vancomycin susceptibility. Genomic analyses provided insights into the molecular mechanisms driving resistance emergence, including the slowing of the molecular clock rate in response to heightened antimicrobial consumption. Conclusions In conclusion, this study the highlights the complex dynamics between AMR and antimicrobial use at the hospital level. The observed correlation between antimicrobial consumption and the development of less susceptible MRSA strains underscores the importance of antimicrobial stewardship programmes and the establishment of optimal consumption thresholds for mitigating AMR effectively.

Publisher

Oxford University Press (OUP)

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