Modelling addition and replacement mechanisms of plasmid-based beta-lactam resistant E. coli infections

It is unknown whether antibiotic-resistant bacterial infections occur in addition to antibiotic-susceptible bacterial infections, thereby increasing the infection incidence, or whether they replace such infections, leaving total incidence unaffected. Observational longitudinal studies cannot separate both mechanisms. Using plasmid-based beta-lactam resistant E. coli as example, we applied a mathematical neutral null model to investigate whether biological mechanisms implying either a fitness cost or a benefit due to resistance lead to replacement or addition. Fitness costs cause resistant strains to die out if other strain characteristics are maintained equal. Under the assumptions tested, only increased virulence increases the total number of infections, while other of resistance lead to replacement without changing the total number of infections. As there is no biological evidence that plasmid-based beta-lactam resistance increases virulence, these findings suggest that the burden of disease is determined by attributable effects of resistance rather than by an increase in infections.