Dynamical Models of the Interactions Between Vaccination and Antibiotic Resistance

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.