Fluoroquinolone and Multidrug Resistance Trends in NARMS-Monitored Enteric Pathogens, United States, 2004-2021

Objective: To consolidate publicly available United States National Antimicrobial Resistance Monitoring System (NARMS) human isolate data spanning 2004-2021 and comprehensively quantify trends in fluoroquinolone resistance, tetracycline resistance, ceftriaxone resistance, and early-stage azithromycin resistance across four NARMS-monitored enteric bacterial pathogens: nontyphoidal Salmonella, Campylobacter jejuni, Campylobacter coli, and Shigella spp. Methods: Annual resistance percentages were compiled from publicly available CDC, FDA, and USDA NARMS Human Isolates Surveillance Reports and Integrated Reports. Multi-year reference-period averages were assigned to their period midpoint years. Ordinary least-squares linear regression was applied to each pathogen-drug series. Slope estimates, 95% confidence intervals, Pearson correlation coefficients, and p-values were computed. A sensitivity analysis was conducted excluding reference-period midpoint years. Results: Ciprofloxacin decreased susceptibility in Salmonella rose from 2.4% to 11% (slope 0.62 pp/year, 95% CI 0.39-0.85; p less than 0.001). Ciprofloxacin resistance in C. jejuni rose from 21% to 34% (slope 1.68 pp/year, 95% CI 1.10-2.25; p=0.001) and in C. coli from 28% to 45% (slope 2.08 pp/year, 95% CI 0.97-3.19; p=0.007). Shigella showed a 5.8-fold increase (underpowered, n=3). Tetracycline resistance in C. jejuni and C. coli rose significantly. Salmonella multidrug resistance declined (slope -0.34 pp/year; p=0.001) while ceftriaxone resistance rose (slope 0.10 pp/year; p=0.028). Azithromycin-resistant Salmonella isolates detected in 2017 equalled the cumulative total from 2011-2016. Discussion: Fluoroquinolone and tetracycline resistance rose significantly across NARMS-monitored Campylobacter species, while Salmonella showed diverging trends: declining classical multidrug resistance but rising fluoroquinolone and ceftriaxone resistance. The emerging azithromycin resistance signal threatens remaining oral treatment options. These trends support sustained investment in harmonized antimicrobial resistance surveillance and stewardship globally.