Increased Incidence of Antimicrobial-Resistant Nontyphoidal Salmonella Infections, United States, 2004–2016

Felicita Medalla; Weidong Gu; Cindy R. Friedman; Michael Judd; Jason Folster; Patricia M. Griffin; Robert M. Hoekstra

Disclosures

Emerging Infectious Diseases. 2021;27(6):1662-1672. 

In This Article

Results

During 2004–2016, public health laboratories of state and participating local health departments in the 48 contiguous states reported 539,862 culture-confirmed Salmonella infections to LEDS (Appendix Table 1). Among the isolates from these infections, 89% were serotyped; the most common were Enteritidis (20%), Typhimurium (16%), Newport (11%), I 4,[5],12:i:- (4%), and Heidelberg (4%). Public health laboratories in the 48 states submitted 28,265 isolates to NARMS. Of these isolates, 98% were serotyped; the most common were Enteritidis (19%), Typhimurium (16%), Newport (11%), I 4,[5],12:i:- (4%), and Heidelberg (4%).

Clinically Important Resistance and Multidrug Resistance

During 2004–2016, clinically important resistance was detected in 3,546 (12.5%) of 28,265 isolates (Table 1; Appendix Figure 1). Ampicillin-only resistance was detected in 1,857 (6.6%) isolates, ciprofloxacin nonsusceptibility in 854 (3.0%), and ceftriaxone/ampicillin resistance in 835 (3.0%). Only 78 (0.3%) isolates were resistant to ceftriaxone and nonsusceptible to ciprofloxacin; these isolates were included in the 835 categorized as ceftriaxone/ampicillin-resistant. Most (>90%) ciprofloxacin-nonsusceptible isolates had MICs within the intermediate range, 0.12–0.5 (Table 1; Appendix Figure 6).

Of the 28,265 isolates, 2,912 (10.3%) were multidrug resistant (MDR). Of these, 2,633 (90%) had clinically important resistance, which accounted for 74% of the 3,546 isolates with clinically important resistance.

Incidence by Year and Region, 2004–2016

For each resistance category, the trend lines were smoother with model-derived annual estimates of resistance incidence compared with crude rates, particularly when stratified by serotype and region (Figure 1; Appendix Figures 2–5). Crude rates tended to be lower than model-derived estimates because many state-year resistance proportions used in calculating crude rates were 0 because of small sample sizes, whereas the model tended to pull estimates away from 0. Overall, most crude rates were within model-derived 95% CrIs.

Resistance Incidence, 2015–2016

During 2015–2016, the mean annual incidence was 2.38 (95% CrI 1.93–2.86)/100,000 persons for clinically important resistant infections and 1.83 (95% CrI 1.45–2.25)/100,000 persons for MDR infections (Table 2). The 5 major serotypes accounted for 69% of infections with clinically important resistance and 66% with multidrug resistance.

Changes in Resistance Incidence, 2015–2016 versus Reference Periods

The mean annual incidence of infections with any clinically important resistance increased during 2015–2016 compared with 2004–2008; there was no significant change compared with 2010–2014 (Table 2; Figures 2 and 3). Among the resistance categories, the mean annual incidence of ciprofloxacin-nonsusceptible Salmonella infections increased during 2015–2016 compared with both reference periods.

Figure 2.

Estimated changes in the incidence of resistant culture-confirmed nontyphoidal Salmonella infections, by serotype, resistance category, and geographic region, United States, 2015–2016 versus 2004–2008. Estimated changes in resistance incidence (mean and 95% credible intervals of the posterior differences per 100,000 persons/year) were derived using Bayesian hierarchical models. Amp-only, Cef/Amp, and Cipro are mutually exclusive categories of clinically important resistance: Amp-only, resistant to ampicillin but susceptible to ceftriaxone and ciprofloxacin; Cef/Amp, resistant to ceftriaxone and ampicillin; Cipro, nonsusceptible to ciprofloxacin but susceptible to ceftriaxone. Isolates in each category might have resistance to other agents. Multidrug resistance was defined as resistance to ≥3 classes of antimicrobial agents. The "other" category comprised serotypes other than Enteritidis, Typhimurium, Newport, I 4,[5],12:i:-, and Heidelberg. US Census regions were used to define 4 geographic regions (A, all regions; M, Midwest; N, Northeast; S, South; W, West). MDR, multidrug resistant. NTS, all nontyphoidal Salmonella serotypes.

Figure 3.

Estimated changes in the incidence of resistant culture-confirmed nontyphoidal Salmonella infections, by serotype, resistance category, and geographic region, United States, 2015–2016 versus 2010–2014. Estimated changes in resistance incidence (mean and 95% credible intervals of the posterior differences per 100,000 persons/year) were derived using Bayesian hierarchical models. Amp-only, Cef/Amp, and Cipro are mutually exclusive categories of clinically important resistance: Amp-only, resistant to ampicillin but susceptible to ceftriaxone and ciprofloxacin; Cef/Amp, resistant to ceftriaxone and ampicillin; Cipro, nonsusceptible to ciprofloxacin but susceptible to ceftriaxone. Isolates in each category might have resistance to other agents. Multidrug resistance (MDR) was defined as resistance to ≥3 classes of antimicrobial agents. The "other" category comprised serotypes other than Enteritidis, Typhimurium, Newport, I 4,[5],12:i:-, and Heidelberg. US Census regions were used to define 4 geographic regions (A, all regions; M, Midwest; N, Northeast; S, South; W, West). MDR, multidrug resistant; NTS, all nontyphoidal Salmonella serotypes.

Changes in Resistance Incidence, 2015–2016 Versus 2004–2008

The mean annual incidence of Salmonella infections with clinically important resistance increased by 0.68 (95% CrI 0.13–1.24)/100,000 persons (Table 2). By census region, a significant increase in resistance only occurred in the Midwest (Figure 2). By serotype, I 4,[5],12:i:- had an incidence increase of 0.41(95% CrI 0.27–0.56)/100,000 persons, accounting for 37% of the increase in clinically important resistant Salmonella infections (Appendix Table 2). The incidence of resistant I 4,[5],12:i:- infections increased significantly in all 4 regions, with highest increase in the West and Midwest. Enteritidis infections with clinically important resistance increased by 0.29 (95% CrI 0.12–0.47)/100,000 persons, accounting for 26% of the increase in resistant infections. This increase was significant in 3 regions, with highest increase in the Northeast. Infections with clinically important resistance caused by serotypes categorized as other increased by 0.41 (95% CrI 0.12–0.72)/100,000 persons, accounting for 37% of the increase in resistant infections (Figure 2; Appendix Table 2). Typhimurium infections with clinically important resistance decreased (−0.33 [95% CrI –0.58 to −0.07]/100,000 persons).

Although no significant changes were noted in the mean annual incidence of Salmonella infections with multidrug or ampicillin-only resistance, some serotypes did change (Figure 2; Appendix Table 2). MDR I 4,[5],12:i:- infections increased (0.40 [95% CrI 0.24–0.56]/100,000 persons); this change was significant in all 4 regions, with highest increase in the West and Midwest. The incidence of MDR Enteritidis infections also increased (0.13 [95% CrI 0.04–0.23]/100,000 persons). We observed a decrease in Typhimurium infections with multidrug resistance (−0.37 [95% CrI –0.59 to −0.14]/100,000 persons) and ampicillin-only resistance (−0.35 [95% CrI –0.61 to −0.10]/100,000 persons). Serotype I 4,[5],12:i:- infections with ampicillin-only resistance increased (0.35 [95% CrI 0.21–0.50]/100,000 persons); this change was significant in all 4 regions, with highest increase in the West and Midwest.

The mean annual incidence of ciprofloxacin-nonsusceptible Salmonella infections increased by 0.41 (95% CrI 0.22–0.61)/100,000 persons (Table 2). Ciprofloxacin-nonsusceptible Enteritidis infections increased by 0.19 (95% CrI 0.05–0.34)/100,000 persons, accounting for 47% of the increase in these infections (Appendix Table 2). This increase was significant in 3 regions, most notably in the Northeast (Figure 2). Ciprofloxacin-nonsusceptible infections caused by serotypes categorized as other increased by 0.16 (95% CrI 0.04–0.29)/100,000 persons, accounting for 38% of the increase in ciprofloxacin-nonsusceptible infections (Figure 2; Appendix Table 2).

Changes in Resistance Incidence, 2015–2016 Versus 2010–2014

The mean annual incidence of Salmonella infections with clinically important resistance did not change compared with the previous 5 years. However, the mean annual incidence of ciprofloxacin-nonsusceptible Salmonella infections increased by 0.29 (95% CrI 0.02–0.52)/100,000 persons (Table 2); by region, the increase was significant only in the Midwest (Figure 3). Ciprofloxacin-nonsusceptible Enteritidis infections increased by 0.16 (95% CrI 0.02–0.32)/100,000 persons, accounting for 57% of the increase in ciprofloxacin-nonsusceptible infections (Appendix Table 3).

Extrapolation to the US Population

Compared with the number of infections for 2004–2008, an estimated ≈63,000 more Salmonella infections with clinically important resistance occurred each year during 2015–2016, from an average of ≈159,000 to ≈222,000; more than half were ciprofloxacin-nonsusceptible (Table 3). Compared with the number of infections for previous 5 years, an estimated ≈56,000 more Salmonella infections with clinically important resistance occurred each year during 2015–2016; more than half were ciprofloxacin-nonsusceptible.

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