Clinical Outcomes of Patients With Nontyphoidal Salmonella Infections by Isolate Resistance-Foodborne Diseases Active Surveillance Network, 10 US Sites, 2004-2018.

BACKGROUND: Nontyphoidal Salmonella causes an estimated 1.35 million US infections annually. Antimicrobial-resistant strains are a serious public health threat. We examined the association between resistance and the clinical outcomes of hospitalization, length-of-stay ≥3 days, and death. METHODS: We linked epidemiologic data from the Foodborne Diseases Active Surveillance Network with antimicrobial resistance data from the National Antimicrobial Resistance Monitoring System (NARMS) for nontyphoidal Salmonella infections from 2004 to 2018. We defined any resistance as resistance to ≥1 antimicrobial and clinical resistance as resistance to ampicillin, azithromycin, ceftriaxone, ciprofloxacin, or trimethoprim-sulfamethoxazole (for the subset of isolates tested for all 5 agents). We compared outcomes before and after adjusting for age, state, race/ethnicity, international travel, outbreak association, and isolate serotype and source. RESULTS: Twenty percent of isolates (1105/5549) had any resistance, and 16% (469/2969) had clinical resistance. Persons whose isolates had any resistance were more likely to be hospitalized (31% vs 28%, P = .01) or have length-of-stay ≥3 days (20% vs 16%, P = .01). Deaths were rare but more common among those with any than no resistance (1.0% vs 0.4%, P = .01). Outcomes for patients whose isolates had clinical resistance did not differ significantly from those with no resistance. After adjustment, any resistance (adjusted odds ratio 1.23, 95% confidence interval 1.04-1.46) remained significantly associated with hospitalization. CONCLUSIONS: We observed a significant association between nontyphoidal Salmonella infections caused by resistant pathogens and likelihood of hospitalization. Clinical resistance was not associated with poorer outcomes, suggesting that factors other than treatment failure (eg, strain virulence, strain source, host factors) may be important.

Typhoid Fever in the US Pediatric Population, 1999-2015: Opportunities for Improvement.

BACKGROUND: Typhoid fever in the United States is acquired primarily through international travel by unvaccinated travelers. There is currently no typhoid vaccine licensed in the United States for use in children <2 years. METHODS: We reviewed Salmonella enterica serotype Typhi infections reported to the Centers for Disease Control and Prevention (CDC) and antimicrobial-resistance data on Typhi isolates in CDC's National Antimicrobial Resistance Monitoring System from 1999 through 2015. RESULTS: 5131 cases of typhoid fever were diagnosed and 5004 Typhi isolates tested for antimicrobial susceptibility. Among 1992 pediatric typhoid fever patients, 1616 (81%) had traveled internationally within 30 days of illness onset, 1544 (81%) of 1906 were hospitalized (median duration, 6 days; range, 0-50), and none died. Forty percent (799) were <6 years old; 12% were <2 years old. Based on age and travel destination, 1435 (83%) of 1722 pediatric patients were vaccine-eligible; only 68 (5%) of 1361 were known to be vaccinated. Of 2003 isolates tested for antimicrobial susceptibility, 1216 (61%) were fluoroquinolone-nonsusceptible, of which 272 (22%) were also resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant [MDR]). All were susceptible to ceftriaxone and azithromycin. MDR and fluoroquinolone-nonsusceptible isolates were more common in children than adults (16% vs 9%, P < .001, and 61% vs 54%, P < .001, respectively). Fluoroquinolone nonsusceptibility was more common among travel-associated than domestically acquired cases (70% vs 17%, P < .001). CONCLUSIONS: Approximately 95% of currently vaccine-eligible pediatric travelers were unvaccinated, and antimicrobial-resistant infections were common. New public health strategies are needed to improve coverage with currently licensed vaccines. Introduction of an effective pretravel typhoid vaccine for children <2 years could reduce disease burden and prevent drug-resistant infections.

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

Salmonella is a major cause of foodborne illness in the United States, and antimicrobial-resistant strains pose a serious threat to public health. We used Bayesian hierarchical models of culture-confirmed infections during 2004-2016 from 2 Centers for Disease Control and Prevention surveillance systems to estimate changes in the national incidence of resistant nontyphoidal Salmonella infections. Extrapolating to the United States population and accounting for unreported infections, we estimated a 40% increase in the annual incidence of infections with clinically important resistance (resistance to ampicillin or ceftriaxone or nonsusceptibility to ciprofloxacin) during 2015-2016 (≈222,000 infections) compared with 2004-2008 (≈159,000 infections). Changes in the incidence of resistance varied by serotype. Serotypes I 4,[5],12:i:- and Enteritidis were responsible for two thirds of the increased incidence of clinically important resistance during 2015-2016. Ciprofloxacin-nonsusceptible infections accounted for more than half of the increase. These estimates can help in setting targets and priorities for prevention.

Update on Extensively Drug-Resistant Salmonella Serotype Typhi Infections Among Travelers to or from Pakistan and Report of Ceftriaxone-Resistant Salmonella Serotype Typhi Infections Among Travelers to Iraq - United States, 2018-2019.

Ceftriaxone-resistant Salmonella enterica serotype Typhi (Typhi), the bacterium that causes typhoid fever, is a growing public health threat. Extensively drug-resistant (XDR) Typhi is resistant to ceftriaxone and other antibiotics used for treatment, including ampicillin, chloramphenicol, ciprofloxacin, and trimethoprim-sulfamethoxazole (1). In March 2018, CDC began enhanced surveillance for ceftriaxone-resistant Typhi in response to an ongoing outbreak of XDR typhoid fever in Pakistan. CDC had previously reported the first five cases of XDR Typhi in the United States among patients who had spent time in Pakistan (2). These illnesses represented the first cases of ceftriaxone-resistant Typhi documented in the United States (3). This report provides an update on U.S. cases of XDR typhoid fever linked to Pakistan and describes a new, unrelated cluster of ceftriaxone-resistant Typhi infections linked to Iraq. Travelers to areas with endemic Typhi should receive typhoid vaccination before traveling and adhere to safe food and water precautions (4). Treatment of patients with typhoid fever should be guided by antimicrobial susceptibility testing whenever possible (5), and clinicians should consider travel history when selecting empiric therapy.

Emergence of Extensively Drug-Resistant Salmonella Typhi Infections Among Travelers to or from Pakistan - United States, 2016-2018.

In February 2018, a typhoid fever outbreak caused by Salmonella enterica serotype Typhi (Typhi), resistant to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, fluoroquinolones, and third-generation cephalosporins, was reported in Pakistan. During November 2016-September 2017, 339 cases of this extensively drug-resistant (XDR) Typhi strain were reported in Pakistan, mostly in Karachi and Hyderabad; one travel-associated case was also reported from the United Kingdom (1). More cases have been detected in Karachi and Hyderabad as surveillance efforts have been strengthened, with recent reports increasing the number of cases to 5,372 (2). In the United States, in response to the reports from Pakistan, enhanced surveillance identified 29 patients with typhoid fever who had traveled to or from Pakistan during 2016-2018, including five with XDR Typhi. Travelers to areas with endemic disease, such as South Asia, should be vaccinated against typhoid fever before traveling and follow safe food and water practices. Clinicians should be aware that most typhoid fever infections in the United States are fluoroquinolone nonsusceptible and that the XDR Typhi outbreak strain associated with travel to Pakistan is only susceptible to azithromycin and carbapenems.

Changing Patterns in Enteric Fever Incidence and Increasing Antibiotic Resistance of Enteric Fever Isolates in the United States, 2008-2012.

BACKGROUND: Enteric fever in the United States has been primarily associated with travel and with worrisome changes in global patterns of antimicrobial resistance. We present the first comprehensive report of National Typhoid and Paratyphoid Fever Surveillance System (NTPFS) data for a 5-year period (2008-2012). METHODS: We reviewed data on laboratory-confirmed cases reported to NTPFS, and related antimicrobial susceptibility results of Salmonella Typhi and Paratyphi A isolates sent for testing by participating public health laboratories to the Centers for Disease Control and Prevention's National Antimicrobial Resistance Monitoring System laboratory. RESULTS: During 2008-2012, 2341 enteric fever cases were reported, 80% typhoid and 20% paratyphoid A. The proportion caused by paratyphoid A increased from 16% (2008) to 22% (2012). Foreign travel within 30 days preceding illness onset was reported by 1961 (86%) patients (86% typhoid and 92% paratyphoid A). Travel to southern Asia was common (82% for typhoid, 97% for paratyphoid A). Among 1091 (58%) typhoid and 262 (56%) paratyphoid A isolates tested for antimicrobial susceptibility, the proportion resistant to nalidixic acid (NAL-R) increased from 2008 to 2012 (Typhi, 60% to 68%; Paratyphi A, 91% to 94%). Almost all NAL-R isolates were resistant or showed decreased susceptibility to ciprofloxacin. Resistance to at least ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug resistant [MDR]) was limited to Typhi isolates, primarily acquired in southern Asia (13%). Most MDR isolates were also NAL-R. CONCLUSIONS: Enteric fever in the United States is primarily associated with travel to southern Asia, and increasing resistance is adding to treatment challenges. A bivalent typhoid and paratyphoid vaccine is needed.

Estimated Incidence of Antimicrobial Drug-Resistant Nontyphoidal Salmonella Infections, United States, 2004-2012.

Salmonella infections are a major cause of illness in the United States. The antimicrobial agents used to treat severe infections include ceftriaxone, ciprofloxacin, and ampicillin. Antimicrobial drug resistance has been associated with adverse clinical outcomes. To estimate the incidence of resistant culture-confirmed nontyphoidal Salmonella infections, we used Bayesian hierarchical models of 2004-2012 data from the Centers for Disease Control and Prevention National Antimicrobial Resistance Monitoring System and Laboratory-based Enteric Disease Surveillance. We based 3 mutually exclusive resistance categories on susceptibility testing: ceftriaxone and ampicillin resistant, ciprofloxacin nonsusceptible but ceftriaxone susceptible, and ampicillin resistant but ceftriaxone and ciprofloxacin susceptible. We estimated the overall incidence of resistant infections as 1.07/100,000 person-years for ampicillin-only resistance, 0.51/100,000 person-years for ceftriaxone and ampicillin resistance, and 0.35/100,000 person-years for ciprofloxacin nonsusceptibility, or ≈6,200 resistant culture-confirmed infections annually. These national estimates help define the magnitude of the resistance problem so that control measures can be appropriately targeted.

Increase in resistance to ceftriaxone and nonsusceptibility to ciprofloxacin and decrease in multidrug resistance among Salmonella strains, United States, 1996-2009.

BACKGROUND: Salmonella is a major bacterial pathogen transmitted commonly through food. Increasing resistance to antimicrobial agents (e.g., ceftriaxone, ciprofloxacin) used to treat serious Salmonella infections threatens the utility of these agents. Infection with antimicrobial-resistant Salmonella has been associated with increased risk of severe infection, hospitalization, and death. We describe changes in antimicrobial resistance among nontyphoidal Salmonella in the United States from 1996 through 2009. METHODS: The Centers for Disease Control and Prevention's National Antimicrobial Resistance Monitoring System conducts surveillance of resistance among Salmonella isolated from humans. From 1996 through 2009, public health laboratories submitted isolates for antimicrobial susceptibility testing. We used interpretive criteria from the Clinical and Laboratory Standards Institute and defined isolates with ciprofloxacin resistance or intermediate susceptibility as nonsusceptible to ciprofloxacin. Using logistic regression, we modeled annual data to assess changes in antimicrobial resistance. RESULTS: From 1996 through 2009, the percentage of nontyphoidal Salmonella isolates resistant to ceftriaxone increased from 0.2% to 3.4% (odds ratio [OR]=20, 95% confidence interval [CI] 6.3-64), and the percentage with nonsusceptibility to ciprofloxacin increased from 0.4% to 2.4% (OR=8.3, 95% CI 3.3-21). The percentage of isolates that were multidrug resistant (resistant to ≥3 antimicrobial classes) decreased from 17% to 9.6% (OR=0.6, 95% CI 0.5-0.7), which was driven mainly by a decline among serotype Typhimurium. However, multidrug resistance increased from 5.9% in 1996 to a peak of 31% in 2001 among serotype Newport and increased from 12% in 1996 to 26% in 2009 (OR=2.6, 95% CI 1.1-6.2) among serotype Heidelberg. CONCLUSIONS: We describe an increase in resistance to ceftriaxone and nonsusceptibility to ciprofloxacin and an overall decline in multidrug resistance. Trends varied by serotype. Because of evidence that antimicrobial resistance among Salmonella is predominantly a consequence of antimicrobial use in food animals, efforts are needed to reduce unnecessary use, especially of critically important agents.

Epidemiology and Antimicrobial Resistance of Campylobacter Infections in the United States, 2005-2018.

Background: Campylobacter is the most common cause of bacterial diarrhea in the United States; resistance to macrolides and fluoroquinolones limits treatment options. We examined the epidemiology of US Campylobacter infections and changes in resistance over time. Methods: The Foodborne Diseases Active Surveillance Network receives information on laboratory-confirmed Campylobacter cases from 10 US sites, and the National Antimicrobial Resistance Monitoring System receives a subset of isolates from these cases for antimicrobial susceptibility testing. We estimated trends in incidence of Campylobacter infection, adjusting for sex, age, and surveillance changes attributable to culture-independent diagnostic tests. We compared percentages of isolates resistant to erythromycin or ciprofloxacin during 2005-2016 with 2017-2018 and used multivariable logistic regression to examine the association of international travel with resistance. Results: Adjusted Campylobacter incidence remained stable or decreased for all groups analyzed since 2012. Among 2449 linked records in 2017-2018, the median patient age was 40.2 years (interquartile range, 21.6-57.8 years), 54.8% of patients were male, 17.2% were hospitalized, and 0.2% died. The percentage of resistant infections increased from 24.5% in 2005-2016 to 29.7% in 2017-2018 for ciprofloxacin (P < .001) and from 2.6% to 3.3% for erythromycin (P = .04). Persons with recent international travel had higher odds than nontravelers of having isolates resistant to ciprofloxacin (adjusted odds ratio [aOR] varied from 1.7 to 10.6 by race/ethnicity) and erythromycin (aOR = 1.7; 95% confidence interval, 1.3-2.1). Conclusions: Campylobacter incidence has remained stable or decreased, whereas resistance to antimicrobials recommended for treatment has increased. Recent international travel increased the risk of resistance.

Ciprofloxacin-resistant Salmonella enterica Serotype Typhi, United States, 1999-2008.

We report 9 ciprofloxacin-resistant Salmonella enterica serotype Typhi isolates submitted to the US National Antimicrobial Resistance Monitoring System during 1999-2008. The first 2 had indistinguishable pulsed-field gel electrophoresis patterns and identical gyrA and parC mutations. Eight of the 9 patients had traveled to India within 30 days before illness onset.

Antimicrobial resistance among invasive nontyphoidal Salmonella enterica isolates in the United States: National Antimicrobial Resistance Monitoring System, 1996 to 2007.

Nontyphoidal salmonellae (NTS) are important causes of community-acquired bloodstream infection. We describe patterns of antimicrobial resistance among invasive NTS in the United States. We compared bloodstream NTS isolates with those from stool submitted to the National Antimicrobial Resistance Monitoring System (NARMS) from 1996 to 2007. We describe antimicrobial resistance among invasive strains by serogroup and serotype. Of the 19,302 NTS isolates, 17,804 (92.2%) were from stool or blood. Of these, 1,050 (5.9%) were bloodstream isolates. The median ages (ranges) of patients with and without bacteremia were 36 (<1 to 97) years and 20 (<1 to 105) years, respectively (P < 0.001). Males (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.06 to 1.38) and those ≥65 years of age were at greater risk for invasive disease. Salmonella enterica serotypes Enteritidis, Typhimurium, and Heidelberg were the most common serotypes isolated from blood; S. enterica serotypes Dublin, Sandiego, and Schwarzengrund were associated with the greatest risk for bloodstream isolation. Of invasive isolates, 208 (19.8%) were resistant to ampicillin, 117 (11.1%) to chloramphenicol, and 26 (2.5%) to trimethoprim-sulfamethoxazole; 28 (2.7%) isolates were resistant to nalidixic acid and 26 (2.5%) to ceftriaxone. Antimicrobial resistance to traditional agents is common. However, the occurrence of nalidixic acid and ceftriaxone resistance among invasive NTS is cause for clinical and public health vigilance.

Antimicrobial susceptibility to azithromycin among Salmonella enterica isolates from the United States.

Due to emerging resistance to traditional antimicrobial agents, such as ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol, azithromycin is increasingly used for the treatment of invasive Salmonella infections. In the present study, 696 isolates of non-Typhi Salmonella collected from humans, food animals, and retail meats in the United States were investigated for antimicrobial susceptibility to azithromycin. Seventy-two Salmonella enterica serotype Typhi isolates from humans were also tested. For each isolate, MICs of azithromycin and 15 other antimicrobial agents were determined by broth microdilution. Among the non-Typhi Salmonella isolates, azithromycin MICs among human isolates ranged from 1 to 32 µg/ml, whereas the MICs among the animal and retail meat isolates ranged from 2 to 16 µg/ml and 4 to 16 µg/ml, respectively. Among Salmonella serotype Typhi isolates, the azithromycin MICs ranged from 4 to 16 µg/ml. The highest MIC observed in the present study was 32 µg/ml, and it was detected in three human isolates belonging to serotypes Kentucky, Montevideo, and Paratyphi A. Based on our findings, we propose an epidemiological cutoff value (ECOFF) for wild-type Salmonella of ≤16 µg/ml of azithromycin. The susceptibility data provided could be used in combination with clinical outcome data to determine tentative clinical breakpoints for azithromycin and Salmonella enterica.

Commensal Escherichia coli isolate resistant to eight classes of antimicrobial agents in the United States.

To increase understanding of community-acquired resistance, stool samples from 477 nonhospitalized persons in Maryland and Michigan, from 2004 to 2008, were screened for ceftriaxone resistance. Seven (1.5%) yielded ceftriaxone-resistant Escherichia coli; one isolate was resistant to all eight antimicrobial classes routinely tested: aminoglycosides, ß-lactam/ß-lactamase inhibitor combinations, cephems, penicillins, folate pathway inhibitors, phenicols, quinolones, and tetracyclines. The extensively resistant isolate was from a 50-year-old woman who denied antimicrobial use, hospitalization, or international travel within 6 months. Meat (beef, chicken, and pork) and eggs were consumed within 1 month before stool collection. Further studies are warranted to understand potential sources, including the food supply, of resistant E. coli.

Evaluation of antimicrobial resistance phenotypes for predicting multidrug-resistant Salmonella recovered from retail meats and humans in the United States.

Although multidrug-resistant (MDR) non-Typhi Salmonella (NTS) strains are a concern in food production, determining resistance to multiple antimicrobial agents at slaughter or processing may be impractical. Single antimicrobial resistance results for predicting multidrug resistance are desirable. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were used to determine each antimicrobial agent's ability to predict MDR phenotypes of human health significance: ACSSuT (resistance to at least ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, tetracycline) in NTS isolates, and MDR-AmpC-SN (resistance to ACSSuT, additional resistance to amoxicillin-clavulanate and to ceftiofur, and decreased susceptibility [MIC >= 2 microg/ml] to ceftriaxone) in NTS serotype Newport. The U.S. National Antimicrobial Resistance Monitoring System determined MICs to 15 or more antimicrobial agents for 9,955 NTS isolates from humans from 1999 to 2004 and 689 NTS isolates from retail meat from 2002 to 2004. A total of 847 (8.5%) human and 26 (3.8%) retail NTS isolates were ACSSuT; 995 (10.0%) human and 16 (2.3%) retail isolates were serotype Newport. Among Salmonella Newport, 204 (20.5%) human and 9 (56.3%) retail isolates were MDR-AmpC-SN. Chloramphenicol resistance provided the highest PPVs for ACSSuT among human (90.5%; 95% confidence interval, 88.4 to 92.3) and retail NTS isolates (96.3%; 95% confidence interval, 81.0 to 99.9). Resistance to ceftiofur and to amoxicillin-clavulanate and decreased susceptibility to ceftriaxone provided the highest PPVs (97.1, 98.1, and 98.6%, respectively) for MDR-AmpC-SN from humans. High PPVs for these agents applied to retail meat MDR-AmpC-SN, but isolate numbers were lower. Variations in MIC results may complicate ceftriaxone's predictive utility. Selecting specific antimicrobial resistance offers practical alternatives for predicting MDR phenotypes. Chloramphenicol resistance works best for ACSSuT-NTS, and resistance to ceftiofur, amoxicillin-clavulanate, or chloramphenicol works best for MDR-AmpC-SN.

Salmonella isolates with decreased susceptibility to extended-spectrum cephalosporins in the United States.

OBJECTIVE: We describe the antimicrobial susceptibility to extended-spectrum cephalosporins in non-Typhi Salmonella (NTS) isolated from humans in the United States and explore resistance mechanisms for isolates displaying decreased susceptibility to ceftriaxone or ceftiofur. We further explore the concordance between the newly revised Clinical and Laboratory Standards Institute (CLSI) breakpoints for ceftriaxone and the presence of a ß-lactamase. METHODS: In 2005 and 2006, public health laboratories in all U.S. state health departments forwarded every 20th NTS isolate from humans to Centers for Disease Control and Prevention as part of the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. Isolates displaying decreased susceptibility (MIC ≥ 2 mg/L) to ceftriaxone or ceftiofur were included in the study. The presence of ß-lactamase genes was investigated by polymerase chain reaction amplification and sequencing, targeting six different genes (bla(TEM), bla(OXA), bla(SHV), bla(CTX-M), bla(PSE), and bla(CMY)). Plasmid location of bla(CMY) was confirmed by transforming plasmids into Escherichia coli. RESULTS: Among the 4236 isolates of NTS submitted to NARMS in 2005 and 2006, 175 (4.1%) displayed decreased susceptibility to either ceftriaxone or ceftiofur. By polymerase chain reaction screening, one or more ß-lactamase genes could be detected in 139 (80.8%) isolates. The most prevalent resistance mechanism detected was the AmpC ß-lactamase gene bla(CMY.) Other ß-lactamase genes detected included 11 bla(TEM-1), 3 bla(PSE-1), 2 bla(OXA-1), and 1 bla(CTX-M-15). The ceftriaxone MIC values for the bla(CMY)-containing isolates ranged from 4 to 64 mg/L; all bla(CMY)-bearing isolates were classified as ceftriaxone resistant according to current CLSI guidelines. CONCLUSIONS: Among NTS isolates submitted to NARMS in 2005 and 2006, cephamycinase ß-lactamases are the predominant cause of decreased susceptibility to ceftriaxone. The fact that all bla(CMY)-containing isolates were classified as resistant to ceftriaxone (MIC ≥ 4 mg/L) supports the newly revised CLSI breakpoints for cephalosporins and Enterobacteriaceae.

Emergence of plasmid-mediated quinolone resistance among non-Typhi Salmonella enterica isolates from humans in the United States.

Plasmid-mediated quinolone resistance determinants are emerging among gram-negative pathogens. Here we report results of a retrospective study investigating the prevalence of aac(6')-Ib-cr, qepA, and qnr genes among 19,010 human isolates of non-Typhi Salmonella enterica collected in the United States from 1996 to 2006.

Laboratory-based surveillance of paratyphoid fever in the United States: travel and antimicrobial resistance.

BACKGROUND: The incidence of paratyphoid fever, including paratyphoid fever caused by antimicrobial-resistant strains, is increasing globally. However, the epidemiologic and laboratory characteristics of paratyphoid fever in the United States have never been studied. METHODS: We attempted to interview all patients who had been infected with laboratory-confirmed Salmonella serotypes Paratyphi A, Paratyphi B, or Paratyphi C in the United States with specimens collected from 1 April 2005 through 31 March 2006. At the Centers for Disease Control and Prevention (CDC), isolates underwent serotype confirmation, antimicrobial susceptibility testing, and pulsed-field gel electrophoresis typing. RESULTS: Of 149 patients infected with Salmonella Paratyphi A, we obtained epidemiologic information for 89 (60%); 55 (62%) of 86 were hospitalized. Eighty-five patients (96%) reported having travel internationally, and 80 (90%) had traveled to South Asia. Of the 146 isolates received at the CDC, 127 (87%) were nalidixic acid resistant; nalidixic acid resistance was associated with travel to South Asia (odds ratio, 17.0; 95% confidence interval, 3.8-75.9). All nalidixic acid-resistant isolates showed decreased susceptibility to ciprofloxacin (minimum inhibitory concentration, > or = 0.12 microg/mL). Of 49 patients infected with Salmonella Paratyphi B, only 12 (24%) were confirmed to have Paratyphi B when tested at the CDC. Four (67%) of 6 patients were hospitalized, and 5 (83%) reported travel (4 to the Andean region of South America). One case of Salmonella Paratyphi C infection was reported in a traveler to West Africa with a urinary tract infection. CONCLUSIONS: Physicians should be aware of the increasing incidence of infection due to Salmonella Paratyphi A and treatment options given its widespread antimicrobial resistance. A paratyphoid fever vaccine is urgently needed. Continued surveillance for paratyphoid fever will help guide future prevention and treatment recommendations.

Distribution of multidrug-resistant human isolates of MDR-ACSSuT Salmonella Typhimurium and MDR-AmpC Salmonella Newport in the United States, 2003-2005.

PURPOSE: Multidrug-resistant (MDR) Salmonella strains are associated with excess bloodstream infections, hospitalizations, and deaths compared with pansusceptible strains. Bovine products are sometimes a source of MDR Salmonella. To generate hypotheses for regional differences in risk factors for human infection, we analyzed distributions of the two most prevalent MDR Salmonella phenotypes in the United States, 2003-2005: (i) MDR-ACSSuT (resistant to at least ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline) Typhimurium; (ii) MDR-AmpC (resistant to at least ampicillin, chloramphenicol, streptomycin, sulfonamides, tetracycline, amoxicillin/clavulanic acid, and ceftiofur, and with decreased susceptibility to ceftriaxone) Newport. MATERIALS AND METHODS: Participating public health laboratories in all states forwarded every 20th Salmonella isolate from humans to the National Antimicrobial Resistance Monitoring System for Enteric Bacteria for antimicrobial susceptibility testing. Among the serotypes Typhimurium and Newport isolates submitted 2003-2005, pansusceptible, MDR-ACSSuT Typhimurium, and MDR-AmpC Newport were identified. Patterns of resistance, demographic factors, and cattle density were compared across regions. RESULTS: Of 1195 serotype Typhimurium isolates, 289 (24%) were MDR-ACSSuT. There were no significant differences in region, age, or sex distribution for pansusceptible versus MDR-ACSSuT Typhimurium. Of 612 serotype Newport isolates, 97 (16%) were MDR-AmpC, but the percentage of MDR-AmpC isolates varied significantly across regions: South 3%, Midwest 28%, West 32%, and Northeast 38% (p < 0.0001). The South had the lowest percentage of MDR-AmpC Newport isolates and also the lowest density of milk cows. More Newport isolates were MDR-AmpC in the 10 states with the highest milk cow density compared with the remaining states. Overall, 22% of pansusceptible Newport isolates but only 7% of MDR-AmpC Newport isolates were from patients <2 years of age. For both serotypes, MDR phenotypes had less seasonal variation than pansusceptible phenotypes. CONCLUSION: This is the first analysis of the distribution of clinically important MDR Salmonella isolates in the United States. MDR-ACSSuT Typhimurium was evenly distributed across regions. However, MDR-AmpC Newport was less common in the South and in children <2 years of age. Information on individuals' exposures is needed to fully explain the observed patterns.

Bayesian hierarchical model of ceftriaxone resistance proportions among Salmonella serotype Heidelberg infections.

The National Antimicrobial Resistance Monitoring System (NARMS) at the Centers for Disease Control and Prevention tracks resistance among Salmonella infections. The annual number of Salmonella isolates of a particular serotype from states may be small, making direct estimation of resistance proportions unreliable. We developed a Bayesian hierarchical model to improve estimation by borrowing strength from relevant sampling units. We illustrate the models with different specifications of spatio-temporal interaction using 2004-2013 NARMS data for ceftriaxone-resistant Salmonella serotype Heidelberg. Our results show that Bayesian estimates of resistance proportions were smoother than observed values, and the difference between predicted and observed proportions was inversely related to the number of submitted isolates. The model with interaction allowed for tracking of annual changes in resistance proportions at the state level. We demonstrated that Bayesian hierarchical models provide a useful tool to examine spatio-temporal patterns of small sample size such as those found in NARMS.

Plasmid-mediated quinolone resistance in non-Typhi serotypes of Salmonella enterica.

BACKGROUND: Serious infections with Salmonella species are often treated with fluoroquinolones or extended-spectrum beta-lactams. Increasingly recognized in Enterobacteriaceae, plasmid-mediated quinolone resistance is encoded by qnr genes. Here, we report the presence of qnr variants in human isolates of non-Typhi serotypes of Salmonella enterica (hereafter referred to as non-Typhi Salmonella) from the United States National Antimicrobial Resistance Monitoring System for Enteric Bacteria. METHODS: All non-Typhi Salmonella specimens from the United States National Antimicrobial Resistance Monitoring System for Enteric Bacteria collected from 1996 to 2003 with ciprofloxacin minimum inhibitory concentrations > or = 0.06 microg/mL (233 specimens) and a subset with minimum inhibitory concentrations < or = 0.03 microg/mL (102 specimens) were screened for all known qnr genes (A, B, and S) by polymerase chain reaction. For isolates with positive results, qnr and quinolone resistance-determining region sequences were determined. Plasmids containing qnr genes were characterized by conjugation or transformation. RESULTS: Conjugative plasmids harboring qnrB variants were detected in 7 Salmonella enterica serotype Berta isolates and 1 Salmonella enterica serotype Mbandaka isolate. The S. Mbandaka plasmid also had an extended-spectrum beta -lactamase. Variants of qnrS on nonconjugative plasmids were detected in isolates of Salmonella enterica serotype Anatum and Salmonella enterica serotype Bovismorbificans. CONCLUSIONS: Plasmid-mediated quinolone resistance appears to be widely distributed, though it is still uncommon in non-Typhi Salmonella isolates from the United States, including strains that are quinolone susceptible by the criteria of the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards). The presence of this gene in non-Typhi Salmonella that causes infection in humans suggests potential for spread through the food supply, which is a public health concern.