Within-host competition modulates pneumococcal antibiotic resistance in the pre-vaccination era

Abstract

BackgroundAntibiotic treatment is a key tool in the fight against pneumococcal infections. However, the ongoing emergence of antibiotic resistant strains and high frequencies of antibiotic resistance of pneumococci pose a major public health challenge. How and which ecological and evolutionary mechanisms help maintain the coexistence of strains susceptible and resistant to antibiotic treatment remains largely an open question. Methods/resultsExpanding on a Streptococcus pneumoniae modelling framework, we here explore how both between- and within-host mechanisms of transmission can sustain observed levels of pneumococcal resistance to antibiotics in the pre-vaccination era using a stochastic, individual-based model. Our framework considers that within-host competition for co-colonization between resistant and susceptible strains can arise via pre-existing immunity (immunological competition) or intrinsic fitness differences due to resistance costs (ecological competition). We find that beyond stochasticity, host-population structure or movement at the between-host level, competition at the within-host level can explain observed variation in resistance frequencies. ConclusionIn a series of simulated scenarios informed by observed pneumococcal data in the European region, we demonstrate that ecological competition for co-colonization can explain much of the variation in co-existence observed at the country level in the pre-vaccination era. This work expands our understanding of how within-host pneumococcal competition facilitates the maintenance of antibiotic resistance in the pre-vaccination era. The demonstration of the effects of such underlying, often unmeasured competition-related components of pneumococcal dynamics improves our understanding of the mechanistic drivers for the emergence and maintenance of antibiotic resistance.