Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora

Abstract

Bystander selection—the selective pressure for resistance exerted by antibiotics on microbes that are not the target pathogen of treatment—is critical to understanding the total impact of broad-spectrum antibiotic use on pathogenic bacterial species that are often carried asymptomatically. However, to our knowledge, this effect has never been quantified. We quantify bystander selection for resistance for a range of clinically relevant antibiotic–species pairs as the proportion of all antibiotic exposures received by a species for conditions in which that species was not the causative pathogen (“proportion of bystander exposures”). Data sources include the 2010–2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, the Human Microbiome Project, and additional carriage and etiological data from existing literature. For outpatient prescribing in the United States, we find that this proportion over all included antibiotic classes is over 80% for eight of nine organisms of interest. Low proportions of bystander exposure are often associated with infrequent bacterial carriage or concentrated prescribing of a particular antibiotic for conditions caused by the species of interest. Applying our results, we roughly estimate that pneumococcal conjugate vaccination programs result in nearly the same proportional reduction in total antibiotic exposures of Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli, despite the latter two organisms not being targeted by the vaccine. These results underscore the importance of considering antibiotic exposures of bystanders, in addition to the target pathogen, in measuring the impact of antibiotic resistance interventions.

Stabilising effects of competition and diversity determine vaccine impact on antibiotic resistance evolution

“…A host naturally clears all carried strains at rate u, and is exposed to antibiotic therapy at a country-specific rate τ, which clears the host of sensitive strains only. We assume that the treatment rate is independent of carriage status (29). In the absence of any mechanism maintaining coexistence between sensitive and resistant cells, competitive exclusion is expected-in other words, either resistant or sensitive strains are expected to go to fixation in the population (24,30).…”

The role of “spillover” in antibiotic resistance

“…Second, decreases in the use of an antibiotic may not necessarily lead to declines in resistance to that antibiotic in a target pathogen (13,27,57,58). We do not address co-resistance and cross-selection (59,60), and we assumed that resistance equilibrates on a timescale comparable to the intervention. Previous research has shown that resistance among E. coli , S. pneumoniae , N. gonorrhoeae and other organisms can respond to changes in antibiotic use on the timescale of months (61–64), but the expected delay between a perturbation to antibiotic use and the resulting change in resistance remains a subject of active study (14,61,65,66).…”

Hygiene Hampers Competitive Release of Resistant Bacteria in the Commensal Microbiota

“…A key task is to manage collateral antibiotic exposure of the commensal microbiota, of which medically important bacteria are often a part. Indeed, a recent analysis found that such 'bystander selection' dominates antibiotic exposure for common human pathogens (6).…”