Differences in antimicrobial resistance gene abundance and microbial diversity of the gut microbiome in patients on antibiotics enrolled in a clinical trial.

BACKGROUND

Understanding how the gut microbiome adapts on exposure to individual antibiotics, with respect to antimicrobial resistance gene (ARG) enrichment, is important.

OBJECTIVES

To characterise the changes that occur in the gut microbiome of patients enrolled in an antibiotic clinical trial and to propose methods in which to embed gut microbiome analysis into clinical trials.

DESIGN

This was a prospective cohort study of hospitalised patients who were successfully enrolled and randomised into two clinical trials between January 2021 to December 2021.

METHODS

Adult patients admitted to the hospital with a bloodstream infection have been randomised to receive either benzylpenicillin, ampicillin, cefazolin, ceftriaxone, piperacillin-tazobactam or meropenem at a single institution. Faecal specimens were collected at enrolment and every second day until discharge. Each specimen underwent DNA sequencing to determine microbial diversity and ARG abundance.

RESULTS

Ten patients (including six females) were included. DNA concentration and sampling quality were markedly lower for rectal swabs compared to stool samples. Relative abundance of was increased in individual patients where treatment included ampicillin, meropenem and piperacillin-tazobactam. Piperacillin-tazobactam also increased the abundance of key beta-lactamase genes ( , , ). Ampicillin increased the abundance of . There were no extended-spectrum beta-lactamase (ESBL) or carbapenemase genes detected in our study. The presence of key anaerobes such as and species appeared to play an important role in colonisation resistance of and .

CONCLUSION

Differential changes in anaerobic bacterial genera on exposure to antibiotics may be a key determinant of colonisation resistance. The pre-analytical phase of microbiome analysis is a critical factor in data quality and interpretation.