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 Streptococcus pneumoniae (pneumococcus) invasive isolates from 27 European countries. We show that the frequency of penicillin resistance in S. pneumoniae 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 S. pneumoniae strains. We used our calibrated models to predict the impact of non–serotype-specific pneumococcal vaccination upon the prevalence of S. pneumoniae carriage, incidence of disease, and frequency of S. pneumoniae 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.

针对细菌性病原体的疫苗可以保护接受者免于感染潜在的抗生素耐药性病原体。然而，通过改变抗生素敏感菌株和抗生素耐药菌株之间的选择性平衡，疫苗也可能在未接种疫苗的个体中抑制或传播抗生素耐药性。预测疫苗接种的结果需要知道是什么驱动了耐药细菌病原体的选择，以及是什么维持了抗生素敏感和抗生素耐药细菌菌株的循环。为了解决这个问题，我们使用了 2007 年关于肺炎链球菌青霉素消耗和青霉素不敏感性的数学模型和数据（肺炎球菌）侵入性分离物来自 27 个欧洲国家。我们表明，肺炎链球菌中青霉素耐药的频率可以通过抗生素使用的宿主间多样性、肺炎球菌携带持续时间的遗传多样性或抗生素耐药和抗生素耐药之间的宿主内竞争带来的频率依赖性选择来解释。敏感的肺炎链球菌菌株。我们使用我们的校准模型来预测非血清型特异性肺炎球菌疫苗接种对肺炎链球菌携带率、疾病发病率和肺炎链球菌频率的影响抗生素耐药性。我们发现耐药和药物敏感肺炎球菌菌株之间竞争的相对强度和方向性是疫苗接种是否会促进、抑制或对抗生素耐药性的演变几乎没有影响的最重要决定因素。最后，我们表明病原体传播的国家特定差异极大地改变了疫苗接种的预测影响，强调必须针对特定病原体和环境量身定制用疫苗管理抗生素耐药性的政策。