Population-level mathematical modeling of antimicrobial resistance: a systematic review

Mathematical transmission models are increasingly used to guide public health interventions for infectious diseases, particularly in the context of emerging pathogens; however, the contribution of modeling to the growing issue of antimicrobial resistance (AMR) remains unclear. Here, we systematically evaluate publications on population-level transmission models of AMR over a recent period (2006–2016) to gauge the state of research and identify gaps warranting further work.

We performed a systematic literature search of relevant databases to identify transmission studies of AMR in viral, bacterial, and parasitic disease systems. We analyzed the temporal, geographic, and subject matter trends, described the predominant medical and behavioral interventions studied, and identified central findings relating to key pathogens.

We identified 273 modeling studies; the majority of which (> 70%) focused on 5 infectious diseases (human immunodeficiency virus (HIV), influenza virus, Plasmodium falciparum (malaria), Mycobacterium tuberculosis (TB), and methicillin-resistant Staphylococcus aureus (MRSA)). AMR studies of influenza and nosocomial pathogens were mainly set in industrialized nations, while HIV, TB, and malaria studies were heavily skewed towards developing countries. The majority of articles focused on AMR exclusively in humans (89%), either in community (58%) or healthcare (27%) settings. Model systems were largely compartmental (76%) and deterministic (66%). Only 43% of models were calibrated against epidemiological data, and few were validated against out-of-sample datasets (14%). The interventions considered were primarily the impact of different drug regimens, hygiene and infection control measures, screening, and diagnostics, while few studies addressed de novo resistance, vaccination strategies, economic, or behavioral changes to reduce antibiotic use in humans and animals.