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

Abstract

Bacterial vaccines can protect recipients from contracting potentially antibiotic-resistant infections. But by altering the selective balance between sensitive and resistant strains, vaccines may also suppress--or spread--antibiotic resistance among unvaccinated individuals. Predicting the outcome requires knowing what drives selection for resistance in bacterial pathogens, and in particular, what maintains the circulation of both antibiotic-sensitive and resistant strains of bacteria. Using mathematical modelling, we show that the frequency of penicillin resistance in Streptococcus pneumoniae (pneumococcus) across 27 European countries can be explained by between-host diversity in antibiotic use, heritable diversity in pneumococcal carriage duration, or frequency-dependent selection brought about by within-host competition between resistant and sensitive strains. We use our calibrated models to predict the impact of non-serotype-specific pneumococcal vaccination upon the prevalence of carriage, incidence of disease, and frequency of resistance for S. pneumoniae. We find that the relative strength and directionality of competition between resistant and sensitive pneumococcal strains is the most important determinant of whether vaccination promotes, inhibits, or has little effect upon the evolution of antibiotic resistance. Finally, we show that country-specific differences in pathogen transmission substantially alter the predicted impact of vaccination, highlighting that policies for managing resistance with vaccines must be tailored to a specific pathogen and setting. One sentence summaryFrequency-dependent competition and extrinsically-maintained diversity shape selection for antibiotic resistance following vaccination.