Pneumococcal Competition Modulates Antibiotic Resistance in the Pre-Vaccination Era: A Modelling Study

Abstract

The ongoing emergence of antibiotic resistant strains and high frequencies of antibiotic resistance of Streptococcus pneumoniae poses a major public health challenge. How and which ecological and evolutionary mechanisms maintain the coexistence of antibiotic resistant and susceptible strains remains largely an open question. We developed an individual-based, stochastic model expanding on a previous pneumococci modelling framework. We explore how between- and within-host mechanisms of competition can sustain observed levels of resistance to antibiotics in the pre-vaccination era. 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, population structure or movement, competition at the within-host level can explain observed resistance frequencies. We compare our simulation results to pneumococcal antibiotic resistance data in the European region using approximate Bayesian computation. Our results demonstrate that ecological competition for co-colonization can explain the variation in co-existence of resistant and susceptible pneumococci observed in the pre-vaccination era. Furthermore, we show that within-host pneumococcal competition can facilitate the maintenance of resistance in the pre-vaccination era. Accounting for these competition-related components of pneumococcal dynamics can improve our understanding of drivers for the emergence and maintenance of antibiotic resistance in pneumococci.

A multilocus perspective on the evolutionary dynamics of multistrain pathogens

“…Our analysis provides new insight into 'evolutionarily optimal' vaccine design, complementing a body of work trying to understand how genetically diverse pathogen populations respond to vaccination [70][71][72][73]. Our work shows that the dominant order LD is generally indicative of how many antigens are required to generate a strongly protective immune response.…”

“…Understanding how genetically-diverse pathogen populations respond to vaccination has been a focus of recent work [63][64][65][66]. Our analysis provides some insight into 'evolutionarily optimal' vaccine design, as the type of LD present is generally indicative of how many antigens are required to generate a strongly protective immune response.…”

Factors affecting antimicrobial resistance in Streptococcus pneumoniae following vaccination introduction

“…Increases in erythromycin MICs were observed between 2001-2007 in Massachusetts despite a decline in antimicrobial prescriptions [45,46]. Furthermore, rates of antibiotic consumption were poorly correlated with rates of country-specific resistance in a modelling study of pneumococcal resistance to penicillins and macrolides across 20 European countries [47]. The global spread of particularly successful pneumococci, driven by other evolutionary processes, may account for these discrepancies [23,48].…”

Assessing COVID-19 vaccination strategies in varied demographics using an individual-based model

“…However, incorporating such features comes at the cost of intense computational demands and decreased interpretability of some results, due to the models' complexity. Nonetheless, IBMs have been previously used to simulate the spread of infectious diseases ( 19 – 22 ) and specifically to study the effects of NPIs and vaccination strategies against COVID-19 ( 23 – 30 ). For instance, previous studies have shown that prioritizing vaccination of the elderly could limit future deaths or quality-adjusted life year losses ( 31 ).…”