Modeling the transmission of antibiotic-resistant Enterobacterales in the community: A systematic review

Abstract

Background

Antibiotic-resistant Enterobacterales (ARE) are a public health threat worldwide. Dissemination of these opportunistic pathogens has been largely studied in hospitals. Despite high prevalence of asymptomatic colonization in the community in some regions of the world, less is known about ARE acquisition and spread in this setting. As explaining the community ARE dynamics has not been straightforward, mathematical models can be key to explore underlying phenomena and further evaluate the impact of interventions to curb ARE circulation outside of hospitals.

Methods

We conducted a systematic review of mathematical modeling studies focusing on the transmission of AR-E in the community, excluding models only specific to hospitals. We extracted model features (population, setting), formalism (compartmental, individual-based), biological hypotheses (transmission, infection, antibiotic impact, resistant strain specificities) and main findings. We discussed additional mechanisms to be considered, open scientific questions, and most pressing data needs.

Results

We identified 18 modeling studies focusing on the human transmission of ARE in the community (n=11) or in both community and hospital (n=7). Models aimed at (i) understanding mechanisms driving resistance dynamics; (ii) identifying and quantifying transmission routes; or (iii) evaluating public health interventions to reduce resistance. To overcome the difficulty of reproducing observed ARE dynamics in the community using the classical two-strains competition model, studies proposed to include mechanisms such as within-host strain competition or a strong host population structure. Studies inferring model parameters from longitudinal carriage data were mostly based on models considering the ARE strain only. They showed differences in ARE carriage duration depending on the acquisition mode: returning travelers have a significantly shorter carriage duration than discharged hospitalized patient or healthy individuals. Interestingly, predictions across models regarding the success of public health interventions to reduce ARE rates depended on pathogens, settings, and antibiotic resistance mechanisms. For E. coli, reducing person-to-person transmission in the community had a stronger effect than reducing antibiotic use in the community. For Klebsiella pneumoniae, reducing antibiotic use in hospitals was more efficient than reducing community use.

Conclusions

This study raises the limited number of modeling studies specifically addressing the transmission of ARE in the community. It highlights the need for model development and community-based data collection especially in low- and middle-income countries to better understand acquisition routes and their relative contribution to observed ARE levels. Such modeling will be critical to correctly design and evaluate public health interventions to control ARE transmission in the community and further reduce the associated infection burden.