Abstract
Antibiotic-resistant infections are a growing threat to human health, but basic features of the eco-evolutionary dynamics remain unexplained. Most prominently, there is no clear mechanism for the long-term coexistence of both drug-sensitive and resistant strains at intermediate levels, a ubiquitous pattern seen in surveillance data. Here we show that accounting for structured or spatially-heterogeneous host populations and variability in antibiotic consumption can lead to persistent coexistence over a wide range of treatment coverages, drug efficacies, costs of resistance, and mixing patterns. Moreover, this mechanism can explain other puzzling spatiotemporal features of drug-resistance epidemiology that have received less attention, such as large differences in the prevalence of resistance between geographical regions with similar antibiotic consumption or that neighbor one another. We find that the same amount of antibiotic use can lead to very different levels of resistance depending on how treatment is distributed in a transmission network. We also identify parameter regimes in which population structure alone cannot support coexistence, suggesting the need for other mechanisms to explain the epidemiology of antibiotic resistance. Our analysis identifies key features of host population structure that can be used to assess resistance risk and highlights the need to include spatial or demographic heterogeneity in models to guide resistance management.
Highlights
Antibiotic resistance is a major threat to our ability to treat bacterial infections
We identify parameter regimes in which population structure alone cannot support coexistence, suggesting the need for other mechanisms to explain the epidemiology of antibiotic resistance
The burden of drug-resistant bacterial infections is rising, and the fear that we are nearing a “post-antibiotic” era has seeped into the public consciousness
Summary
Antibiotic resistance is a major threat to our ability to treat bacterial infections. Individual bacteria that are resistant to multiple classes of antibiotics are common in species such as Streptococcus pneumoniae, Pseudomonas aeruginosa, and Clostridium difficile [2], and nearly untreatable strains of Neisseria gonorrheae [3], Klebsiella pneumoniae [4], and Acinetobacter baumannii [5] have recently been identified. These trends have led to speculations about a “post-antibiotic future”, in which routine medical procedures such as surgeries, childbirth, and dental work might become as high-risk as they were in the pre-WWII era due to a lack of effective antibiotic prophylaxis and treatment [6, 7]. At minimum, be able to explain current trends before being trusted for forecasting, these fundamental disagreements with data have either discouraged efforts to make predictions or led to widespread suspicion of existing predictions (e.g. the Review on Antimicrobial Resistance [10, 11])
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