Background/Objectives: Streptococcus pneumoniae remains a major cause of invasive disease, and antimicrobial resistance is shaped by antibiotic selection and pneumococcal conjugate vaccination. A unified framework is needed to compare proposed mechanisms that maintain coexistence of antibiotic-sensitive and -resistant strains and to interpret post-vaccine resistance trajectories. Methods: We formulated a susceptible–exposed–vaccinated–infectious–recovered (SEVIR) transmission model that tracks antibiotic-sensitive and -resistant pneumococcal infections under vaccination and treatment. The basic reproduction number (R0) was derived using the next-generation matrix method and used to assess local stability of the disease-free equilibrium. Using the same core structure, we evaluated three mechanism-specific extensions: treatment diversity (heterogeneous antibiotic use across host groups), pathogen diversity (serotype/subtype heterogeneity under vaccine targeting), and treatment competition (within-host competition with treatment-induced selection). Results: Treatment diversity generated stable coexistence by creating low-treatment refugia that counterbalanced strong selection in highly treated groups, supporting resistance persistence at moderate population-average treatment. Pathogen diversity reproduced serotype-specific replacement and concentration of resistance within particular subtypes after vaccination. Treatment competition produced nonlinear responses to antibiotic intensity and transient resistance surges. Overall, each mechanism explained a distinct subset of benchmark resistance patterns, suggesting that dominant drivers depend on epidemiological context. Conclusions: Interactions between vaccination, antibiotic pressure, population heterogeneity, pathogen diversity and within-host competition can yield qualitatively different resistance dynamics. Strategies combining high vaccine uptake with targeted antibiotic stewardship are likely required to curb resistance while limiting unintended serotype replacement.
Zhang et al. (Thu,) studied this question.