Analysis of Multi-Antimicrobial Resistance Patterns in U.S. Foodborne Pathogens (2015–2025) Using Data from the NCBI Pathogen Isolates Browser

Antimicrobial resistance (AMR) in foodborne pathogens poses a major threat to global public health and food safety. Using 9393 U.S. isolates of <i>Salmonella enterica</i>, <i>Campylobacter jejuni</i>, and <i>Escherichia coli</i>/<i>Shigella</i> collected from poultry, cattle, and swine between 2015 and 2025 and archived in the NCBI Pathogen Isolates Browser, we applied multivariate statistical analysis to characterize antimicrobial resistance patterns in isolates showing resistance to one to six antimicrobials (AMR-1 to AMR-6). Six antimicrobials-tetracycline, streptomycin, sulfisoxazole, ampicillin, nalidixic acid, and ciprofloxacin-were identified through PCA-guided clustering and frequency profiling as the principal axes of co-resistance across pathogens. Tetracycline emerged as a foundational driver of multidrug resistance, while <i>C. jejuni</i> contributed almost exclusively to single-drug resistance and <i>Salmonella enterica</i> dominated higher-order AMR categories, reflecting species-specific ecological and genomic constraints. Gene analyses revealed a progressive, modular accumulation of resistance determinants, led by efflux pumps (<i>mdsA</i>, <i>mdsB</i>), tetracycline genes (<i>tetA</i>/<i>B</i>/<i>O</i>), aminoglycoside-modifying enzymes, sulfonamide genes (<i>sul1</i>/<i>sul2</i>), quinolone resistance determinants (<i>gyrA</i>, <i>acrF</i>, <i>mdtM</i>), and β-lactamases (<i>bla_EC</i>, <i>bla_OXA</i>, <i>bla_CTX</i>). Together, these results demonstrate that multidrug resistance in U.S. foodborne pathogens evolves through coordinated gene-drug-pathogen interactions rather than isolated events, underscoring the need for integrated surveillance and targeted stewardship strategies focused on the dominant antimicrobials and high-risk foodborne pathogens.