Exposure to antibiotics with anaerobe coverage in later life is associated with higher enteric pathobiont carriage

Objectives: Infections involving enteric bacteria commonly cause hospitalisation and death in long-term residential aged care (LTC) populations. The risk of such infections has been linked with antibiotic-associated depletion of gut anaerobic commensals and the resulting increase in asymptomatic carriage of gut pathobionts. We sought to determine how antibiotic characteristics, particularly activity against anaerobes, influence pathobiont prevalence in LTC residents. Methods: Stool samples from 164 LTC residents (median age: 87.9 years, interquartile range: 81.3–93.0 years) underwent metagenomic analysis. Associations between prior antibiotic exposures (categorised according to anaerobe coverage and type) and gut microbiome characteristics were explored using multivariable models. Results: Of the 164 participants, 138 (84.1%) carried at least one enteric pathobiont. Compared to those with no prior antibiotic exposure, treatment with anaerobe covering (EAC) antibiotics was associated with higher rates of pathobiont carriage (β=1.36, P=0.010) and higher overall pathobiont relative abundance (β=3.53, P=0.013). In contrast, exposure to antibiotics with limited anaerobe coverage (LAC) showed no such associations. Investigation of commonly prescribed EAC and LAC antibiotics (amoxicillin-clavulanate and cefalexin, respectively) were consistent with these findings, with higher detection (β=1.60, P=0.007) and relative abundance (β=3.32, P=0.039) of pathobiont species in amoxicillin-clavulanate recipients. Pathobionts with greater representation included both species with inherent resistance (i.e. Enterococcus faecium) and sensitivity (i.e. Klebsiella pneumoniae) to amoxicillin-clavulanate. Conclusions: Antibiotics that deplete commensal anaerobes are associated with pathobiont prevalence in the gut, even where pathobiont species are sensitive to the administered antibiotic. Off-target disruption of commensal anaerobes should be considered when selecting antibiotic treatments, particularly for LTC individuals.