Wellcome Open Research (May 2024)
MIC distribution analysis identifies differences in AMR between population sub-groups [version 1; peer review: 2 approved]
Abstract
Background Phenotypic data, such as the minimum inhibitory concentrations (MICs) of bacterial isolates from clinical samples, are widely available through routine surveillance. MIC distributions inform antibiotic dosing in clinical care by determining cutoffs to define isolates as susceptible or resistant. However, differences in MIC distributions between patient sub-populations could indicate strain variation and hence differences in transmission, infection, or selection. Methods The Vivli AMR register contains a wealth of MIC and metadata for a vast range of bacteria-antibiotic combinations. Using a generalisable methodology followed by multivariate regression, we explored MIC distribution variations across 4 bacteria, covering 7,135,070 samples, by key population sub-groups such as age, sex and infection type, and over time. Results We found clear differences between MIC distributions across various patient sub-groups for a subset of bacteria-antibiotic pairings. For example, within Staphylococcus aureus, MIC distributions by age group and infection site displayed clear trends, especially for levofloxacin with higher resistance levels in older age groups (odds of 2.17 in those aged 85+ compared to 19–64), which appeared more often in men. This trend could reflect greater use of fluoroquinolones in adults than children but also reveals an increasing MIC level with age, suggesting either transmission differences or accumulation of resistance effects. We also observed high variations by WHO region, and over time, with the latter likely linked to changes in surveillance. Conclusions We found that MIC distributions can be used to identify differences in AMR levels between population sub-groups. Our methodology could be used more widely to unveil hidden transmission sources and effects of antibiotic use in different patient sub-groups, highlighting opportunities to improve stewardship programmes and interventions, particularly at local scales.
