Fluoroquinolone and Multidrug Resistance Trends in NARMS-Monitored Enteric Pathogens, United States, 2004-2021: A Comprehensive Surveillance-Based Time-Series Analysis
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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 (2004-2008 and 2010-2014) were assigned to their period midpoint years. Ordinary least-squares linear regression of resistance percentage against calendar year was applied to each pathogen-drug series. Slope estimates, 95% confidence intervals (CI), Pearson correlation coefficients, and p-values were computed. A sensitivity analysis was conducted excluding reference-period midpoint years to verify trend direction using single-year data only.
Results
Ciprofloxacin decreased susceptibility in Salmonella rose from 2.4% (2004-2008) to 11% (2021) (slope 0.62 percentage points [pp]/year, 95% CI 0.39-0.85; p<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 (1.7% to 9.8%; underpowered, n=3). Tetracycline resistance in C. jejuni and C. coli also rose significantly (slopes 0.73 and 1.22 pp/year, respectively; p<0.01). Salmonella multidrug resistance (MDR, ≥5 drug classes) declined significantly (slope −0.34 pp/year, 95% CI−0.45 to −0.22; p=0.001). Ceftriaxone resistance in Salmonella increased significantly from 0.4% to 2.1% (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 MDR but rising fluoroquinolone and ceftriaxone resistance. The emerging azithromycin resistance signal threatens remaining oral treatment options. These trends, mirroring patterns across Asia-Pacific and Europe, support sustained investment in harmonized antimicrobial resistance surveillance and stewardship globally, consistent with WHO’s Global Action Plan on Antimicrobial Resistance.
Brief description
Analysis of CDC NARMS data (2004-2021) reveals significant fluoroquinolone resistance increases across nontyphoidal Salmonella, Campylobacter jejuni, and Campylobacter coli, with diverging trends in multidrug and ceftriaxone resistance. An early-stage azithromycin resistance signal in Salmonella threatens remaining treatment options with global stewardship implications.
