Modeling the effect of vaccination on selection for antibiotic resistance in <i>Streptococcus pneumonia</i> <i>e</i>.

Abstract

Vaccines against bacterial pathogens can protect recipients from becoming infected with potentially antibiotic-resistant pathogens. However, by altering the selective balance between antibiotic-sensitive and antibiotic-resistant bacterial strains, vaccines may also suppress-or spread-antibiotic resistance among unvaccinated individuals. Predicting the outcome of vaccination requires knowing what drives selection for drug-resistant bacterial pathogens and what maintains the circulation of both antibiotic-sensitive and antibiotic-resistant strains of bacteria. To address this question, we used mathematical modeling and data from 2007 on penicillin consumption and penicillin nonsusceptibility in <i>Streptococcus pneumoniae</i> (pneumococcus) invasive isolates from 27 European countries. We show that the frequency of penicillin resistance in <i>S. pneumoniae</i> 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 antibiotic-resistant and antibiotic-sensitive <i>S. pneumoniae</i> strains. We used our calibrated models to predict the impact of non-serotype-specific pneumococcal vaccination upon the prevalence of <i>S. pneumoniae</i> carriage, incidence of disease, and frequency of <i>S. pneumoniae</i> antibiotic resistance. We found that the relative strength and directionality of competition between drug-resistant and drug-sensitive pneumococcal strains was the most important determinant of whether vaccination would promote, inhibit, or have little effect upon the evolution of antibiotic resistance. Last, we show that country-specific differences in pathogen transmission substantially altered the predicted impact of vaccination, highlighting that policies for managing antibiotic resistance with vaccines must be tailored to a specific pathogen and setting.