Antimicrobial Resistance Patterns of Outpatient Staphylococcus aureus Isolates

IMPORTANCE Oral non-beta-lactam antibiotics are commonly used for empirical therapy of Staphylococcus aureus infections, especially in outpatient settings. However, little is known about potential geographic heterogeneity and temporal trends in the prevalence of S aureus resistance to non-beta-lactams in the US. OBJECTIVE To characterize the spatiotemporal trends of resistance to non-beta-lactam antibiotics among community-onset S aureus infections, including regional variation in resistance rates and geographical heterogeneity in multidrug resistance. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study used data from Veterans Health Administration clinics collected from adult outpatients with S aureus infection in the conterminous 48 states and Washington, DC, from January 1, 2010, to December 31, 2019. Data were analyzed from January to November 2023. EXPOSURES Resistance to lincosamides (clindamycin), tetracyclines, sulfonamides (trimethoprim-sulfamethoxazole [TMP-SMX]), and macrolides. MAIN OUTCOMES AND MEASURES Spatiotemporal variation of S aureus resistance to these 4 classes of non-beta-lactam antibiotics, stratified by methicillin-resistant S aureus (MRSA) and methicillin-sensitive S aureus (MSSA), and subdivided by regions of the US (Northeast, Midwest, South, and West). Trend tests and bivariate mapping were used to determine significant changes in resistant proportions over time and identify counties where rates of resistance to multiple non-beta-lactams were high. RESULTS A total of 382 149 S aureus isolates from 268 214 unique outpatients (mean [SD] age, 63.4 [14.8] years; 252 910 males [94.29%]) were analyzed. There was a decrease in the proportion of MRSA nationwide, from 53.6% in 2010 to 38.8% in 2019. Among MRSA isolates, we observed a significant increase in tetracycline resistance (from 3.6% in 2010 to 12.8% in 2019; P for trend < .001) and TMP-SMX resistance (from 2.6% in 2010 to 9.2% in 2019; P for trend < .001), modest and not significant increases in clindamycin resistance (from 24.2% in 2010 to 30.6% in 2019; P for trend = .34), and a significant decrease in macrolide resistance (from 73.5% in 2010 to 60.2% in 2019; P for trend < .001). Among MSSA isolates, significant upward trends in clindamycin, tetracyclines, and TMP-SMX resistance were observed. For example, tetracycline resistance increased from 3.7% in 2010 to 9.1% in 2019 (P for trend < .001). Regional stratification over time showed that the Northeast had slightly higher rates of clindamycin resistance but lower rates of tetracycline resistance, while the South had notably higher rates of resistance to tetracyclines and TMP-SMX, particularly among MRSA isolates. Bivariate mapping at the county scale did not indicate clear regional patterns of shared high levels of resistance to the 4 classes of antimicrobials studied. CONCLUSIONS AND RELEVANCE In this study of outpatient S aureus isolates, MRSA became less common over the 10-year period, and MRSA isolates were increasingly resistant to tetracyclines and TMP-SMX. Geographic analysis indicated no spatial overlap in counties with high rates of resistance to both tetracyclines and TMP-SMX. Examining the regional spatial variation of antibiotic resistance can inform empirical therapy recommendations and help to understand the evolution of S aureus antibiotic resistance mechanisms.