Abstract
Infections caused by antibiotic-resistant bacteria have become more prevalent during past decades. Yet, it is unknown whether such infections occur in addition to infections with antibiotic-susceptible bacteria, thereby increasing the incidence of infections, or whether they replace such infections, leaving the total incidence unaffected. Observational longitudinal studies cannot separate both mechanisms. Using plasmid-based beta-lactam resistant E. coli as example we applied mathematical modelling to investigate whether seven biological mechanisms would lead to replacement or addition of infections. We use a mathematical neutral null model of individuals colonized with susceptible and/or resistant E. coli, with two mechanisms implying a fitness cost, i.e., increased clearance and decreased growth of resistant strains, and five mechanisms benefitting resistance, i.e., 1) increased virulence, 2) increased transmission, 3) decreased clearance of resistant strains, 4) increased rate of horizontal plasmid transfer, and 5) increased clearance of susceptible E. coli due to antibiotics. Each mechanism is modelled separately to estimate addition to or replacement of antibiotic-susceptible infections. Fitness costs cause resistant strains to die out if other strain characteristics are maintained equal. Under the assumptions tested, increased virulence is the only mechanism that increases the total number of infections. Other benefits of resistance lead to replacement of susceptible infections 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 the number of infections.
Highlights
Using E. coli as example, we developed a mathematical model to investigate whether seven biological characteristics of antibiotic-resistant bacteria (ARB), each linked to either fitness costs or benefits, cause replacement or addition
As there is no biological evidence that the type of resistance in E. coli we studied increases virulence, these findings suggest that the burden of ARB is determined by attributable effects of resistance rather than by an increase in infections
It is unknown to what extent the global increase in infections caused by antibiotic-resistant bacteria (ARB) during the last decades has changed the burden of disease
Summary
It is unknown to what extent the global increase in infections caused by antibiotic-resistant bacteria (ARB) during the last decades has changed the burden of disease. Infections caused by ARB are more difficult to treat, resulting in more adverse health outcomes [2], which increases the healthcare burden. There is an increase in the total number of infections together with attributable harm created by those infection caused by ARB. The increased burden of disease due to resistance results solely from the attributable harm created by resistant compared to susceptible infections, as the total number of infections remains stable. Quantifying the relative contribution of both scenarios is of critical importance for quantifying the burden of disease created by ARB. Longitudinal observational data have been used to estimate the relative importance of addition and replacement [1,3], but the validity of these approaches suffered–inevitably–from other time-dependent changes and between studygroups differences that may influence overall incidence of infections, e.g., changes in medical procedures, population age, antimicrobial stewardship, and infection prevention measures
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