The impact of antibiotic use on transmission of resistant bacteria in hospitals: Insights from an agent-based model

Extensive antibiotic use over the years has led to the emergence and spread of antibiotic resistant bacteria (ARB). Antibiotic resistance poses a major threat to public health since for many infections antibiotic treatment is no longer effective. Hospitals are focal points for ARB spread. Antibiotic use in hospitals exerts selective pressure, accelerating the spread of ARB. We used an agent-based model to explore the impact of antibiotics on the transmission dynamics and to examine the potential of stewardship interventions in limiting ARB spread in a hospital. Agents in the model consist of patients and health care workers (HCW). The transmission of ARB occurs through contacts between patients and HCW and between adjacent patients. In the model, antibiotic use affects the risk of transmission by increasing the vulnerability of susceptible patients and the contagiousness of colonized patients who are treated with antibiotics. The model shows that increasing the proportion of patients receiving antibiotics increases the rate of acquisition non-linearly. The effect of antibiotics on the spread of resistance depends on characteristics of the antibiotic agent and the density of antibiotic use. Antibiotic's impact on the spread increases when the bacterial strain is more transmissible, and decreases as resistance prevalence rises. The individual risk for acquiring ARB increases in parallel with antibiotic density both for patients treated and not treated with antibiotics. Antibiotic treatment in the hospital setting plays an important role in determining the spread of resistance. Interventions to limit antibiotic use have the potential to reduce the spread of resistance, mainly by choosing an agent with a favorable profile in terms of its impact on patient's vulnerability and contagiousness. Methods to measure these impacts of antibiotics should be developed, standardized, and incorporated into drug development programs and approval packages.