Surveillance and Stewardship in the Battle Against Antimicrobial Resistance in U.S. Foodborne Pathogens

A U.S. analysis of antimicrobial resistance in foodborne pathogens (9,393 isolates, 2015–2025) identified six co-resistance axes that shift empiric-therapy choices and raise outbreak risk by consolidating multidrug profiles in livestock-associated strains; U.S. AMR patterns are therefore clinically consequential.

The findings indicate an urgent need to align surveillance and stewardship priorities to detect and limit multidrug-resistance spread.

Statistical models pinpointed six antimicrobials as the dominant co-resistance drivers: tetracycline, streptomycin, sulfisoxazole, ampicillin, nalidixic acid, and ciprofloxacin. These axes distributed unevenly across pathogens: Salmonella concentrated in higher-order multidrug clusters, while Campylobacter largely contributed single-drug resistance signatures. Surveillance therefore should shift toward targeted monitoring of these antimicrobials and pathogen pairings to catch escalation earlier.

Tetracycline emerged as a foundational driver of multidrug resistance, appearing in most high-frequency co-resistance profiles with strong validation confidence. Co-selection is explained by co-located resistance genes on mobile plasmids, efflux-mediated reductions in intracellular drug levels, and plasmid-mediated linkage of tetracycline markers with aminoglycoside, sulfonamide, and β-lactam determinants.

Salmonella showed the strongest tetracycline-linked co-resistance in multidrug isolates; Campylobacter carried primarily tetracycline-dominant single-drug signatures. Reducing tetracycline selection pressure and monitoring its markers could disproportionately lower the multidrug-resistance burden.

Genomic screening detected pervasive efflux pumps alongside tet and sul gene families across resistant isolates, with mdsA/mdsB and tet(A/B/O) commonly co-occurring with sul1/sul2 and aminoglycoside-modifying enzymes. These detection frequencies support using tet and sul loci as operational signals. Routine genomic screens for tet and sul, combined with plasmid and mobile-element characterization, clarify the modular accumulation of resistance determinants and improve early detection of emergent co-resistance modules.

Prioritizing the identified antimicrobials and pathogen–resistance combinations focuses public-health resources on high-yield signals. Practical actions include adapting isolate collection to oversample Salmonella from poultry and swine, implementing routine genomic monitoring of efflux and tet–sul loci, and concentrating mitigation efforts in high-risk production reservoirs to trace and interrupt transmission pathways.

Implementing these surveillance changes should better inform stewardship and therapeutic development and shorten response time during outbreaks.

Key Takeaways:

• Surveillance across 9,393 isolates (2015–2025) identified six co-resistance axes, with tetracycline central to multidrug profiles.
• Salmonella enterica drives most high-order multidrug resistance; Campylobacter primarily accounts for single-drug tetracycline resistance. Poultry, swine, and cattle reservoirs concentrate risk.
• Shift surveillance panels and genomic monitoring to prioritize tetracycline, tet/sul markers, efflux genes, and targeted sampling of Salmonella in high-risk reservoirs to better inform stewardship and empiric therapy choices; next-step prioritization is warranted.