Dissertation
Spatiotemporal and evolutionary dynamics of antimicrobial-resistance in Staphylococcus aureus in the United States
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2026
DOI: 10.25820/etd.008422
Abstract
Although antibiotics are highly effective for treating bacterial infections, the rise of antimicrobial resistance (AMR) represents one of the most pressing public health threats of the 21st century. While antibiotic use remains the primary selective pressure driving AMR, an extended disease ecology framework captures how reciprocal interactions between adapting bacteria and selective pressures arising from changing environmental conditions, host populations, and human behavior shape the spatial and temporal patterns of resistance. Staphylococcus aureus (S. aureus), a leading opportunistic pathogen, has demonstrated increasing resistance to multiple antibiotics, despite declines in methicillin-resistance S. aureus (MRSA) prevalence. Situated within the previously described conceptual framework, this thesis examines the spatiotemporal dynamics and multifaceted drivers of AMR among S. aureus across the United States (U.S.).
Using phenotypic antibiotic susceptibility data from U.S. Veteran Health Administration (VHA) outpatient electronic health records, the spatiotemporal patterns of tetracycline and trimethoprim-sulfamethoxazole (TMP-SMX) resistance among S. aureus cultures were examined at the commuting-zone (CZ) level across the eastern U.S. Substantial within-state heterogeneity was observed in both the relative risks and temporal trends of both resistance phenotypes. Although after classification the number of high risk CZs were limited and most exhibited stationary trends, distinct patterns in the rate and timing of changes in resistance were observed in CZ-specific risk plots. These evolving and geographically variable patterns of AMR at a finer spatial scale highlights the need for local surveillance and outpatient antibiotic stewardship strategies that consider place-based sociodemographic, ecologic, and clinical factors.
Building on these findings, associations between patient- and residential county-level factors and tetracycline and TMP-SMX resistance among S. aureus cultures from VHA outpatients were examined using a nationwide dataset. Prior antibiotic use demonstrated the strongest and most consistent association with both resistance phenotypes. Rurality was generally associated with lower odds of resistance, especially among TMP-SMX-resistant MRSA cultures, whereas methicillin-susceptible S. aureus (MSSA) showed regional variability in the Midwest, suggesting a stronger influence of intensive livestock production or differences in prescribing practices in the rural Midwest. However, between-county variation was not adequately explained by the included county-level covariates, highlighting the need for indicators that more directly capture antibiotic selective pressures and transmission pathways shaping AMR, including the spatial distribution of clonal lineages and their resistance profiles.
Given that S. aureus lineages differ in their resistance determinants and epidemiological characteristics, which may influence their spatial distribution, a nationwide genomic dataset was used to characterize the spatiotemporal patterns of sequence types (ST) and the associated resistance determinants of two high-frequency lineages, ST5 and ST8. Although the community-associated ST8 lineage remained predominant, the diversity of STs increased over time, suggesting either replacement by lower frequency lineages or the dissemination of healthcare-associated ST5 strains into community settings. Distinct trends of antibiotic resistance were also observed, with declines across several antibiotic classes in ST5 and increasing quinolone and TMP-SMX resistance in ST8, consistent with evidence that epidemiological and molecular characteristics between these are becoming increasingly blurred. Time-scaled phylogenies revealed independent acquisition of resistance determinants in ST8 and ST5, with these events coinciding with lineage divergence and geographic expansion across U.S. Census divisions.
Together these studies illustrate the value of examining AMR through an extended disease ecology framework that considers spatial and ecological processes shaping its emergence and spread. The findings highlight substantial geographic heterogeneity in risk and underscore the need for localized, representative surveillance that integrates genomic data to better inform antibiotic stewardship efforts in both healthcare and community settings.
Details
- Title: Subtitle
- Spatiotemporal and evolutionary dynamics of antimicrobial-resistance in Staphylococcus aureus in the United States
- Creators
- Miah Boyle
- Contributors
- Margaret Carrel (Advisor)Michihiko Goto (Committee Member)Andrew Kitchen (Committee Member)Caglar Koylu (Committee Member)Jacob Oleson (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Geography
- Date degree season
- Spring 2026
- DOI
- 10.25820/etd.008422
- Publisher
- University of Iowa
- Number of pages
- xii, 136 pages
- Copyright
- Copyright 2026 Miah Boyle
- Language
- English
- Date submitted
- 04/22/2026
- Description illustrations
- Illustrations, graphs, charts, tables
- Description bibliographic
- Includes bibliographical references (pages 119-136).
- Public Abstract (ETD)
Antibiotics are regularly used to treat bacterial infections. However, their extended use has caused antimicrobial resistance to develop in some bacteria, making these infections more difficult to treat. Rising resistance in the bacteria Staphylococcus aureus (S. aureus), a leading opportunistic pathogen in humans, to commonly used antibiotics is particularly concerning. This dissertation aims to describe how resistance in S. aureus varies across the United States, how it changes over time, and what factors may contribute to these patterns. Using clinical resistance data from S. aureus cases, we showed that the risk of resistance and change over time varied across locations. These results suggest that factors influencing these patterns operate at the local level. We then examined how local county-level factors and patient-level factors were associated with resistance and found that antibiotic use was the primary risk factor, while rural residence was generally associated with lower resistance, although the relationship differed in the Midwest. The variation across counties, however, was still not explained. Using a nationwide genomic dataset, we found that the distribution of different S. aureus strains varied across regions, and strain diversity increased over time. Two common strains also showed different trends of resistance to several antibiotics, with increases in resistance occurring as the strains evolved into new groups and expanded. Because different strains have different resistance profiles, their distribution across space may help explain geographic variation in resistance observed in clinical data. These findings highlight the importance of local surveillance and genomic data to help guide the appropriate use of antibiotics and slow the spread of resistance.
- Academic Unit
- School of Earth, Environment, and Sustainability
- Record Identifier
- 9985176871602771
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