Gulf War Illness (GWI) is a disorder experienced by many veterans of the 1991 Gulf War, with symptoms including fatigue, chronic pain, respiratory and memory problems. Exposure to toxic chemicals during the war, such as oil well fire smoke, pesticides, physiological stress, and nerve agents, is thought to have triggered abnormal neuroinflammatory responses that contribute to GWI. Previous studies have examined the acute effects of combined physiological stress and chemical exposures using GWI rodent models and presented findings related to neuroinflammation and changes in diffusion magnetic resonance imaging (MRI) measures, suggesting a neuroimmune basis for GWI. In the current study, using ex vivo MRI, cytokine mRNA expression, and immunohistological analyses of brain tissues, we examined the brain structure and immune function of a chronic rat model of GWI. Our data showed that a combination of long-term corticosterone treatment (to mimic high physiological stress) and diisopropyl fluorophosphate exposure (to mimic sarin exposure) primed the response to subsequent systemic immune challenge with lipopolysaccharide resulting in elevations of multiple cytokine mRNAs, an increased activated glial population, and disrupted brain microstructure in the cingulate cortex and hippocampus compared to control groups. Our findings support the critical role of neuroinflammation, dysregulated glial activation, and their relationship to disrupted brain microstructural integrity in the pathophysiology of GWI and highlight the unique consequences of long-term combined exposures on brain biochemistry and structural connectivity. © 2024

BACKGROUND: Nontyphoidal Salmonella causes an estimated 1.35 million U.S. 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 2004-2018. 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 five 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 (1,105/5,549) had any resistance and 16% (469/2,969) had clinical resistance. Persons whose isolates had any resistance were more likely to be hospitalized (31% vs. 28%, P=0.01) or have length-of-stay ≥3 days (20% vs. 16%, P=0.01). Deaths were rare, but more common among those with any than no resistance (1.0% vs. 0.4%, P=0.01). 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 (e.g., strain virulence, strain source, host factors) may be important.

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.

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.

COVID-19 vaccines are a critical tool for controlling the ongoing global pandemic. The Food and Drug Administration (FDA) has issued Emergency Use Authorizations for three COVID-19 vaccines for use in the United States.* In large, randomized-controlled trials, each vaccine was found to be safe and efficacious in preventing symptomatic, laboratory-confirmed COVID-19 (1-3). Despite the high level of vaccine efficacy, a small percentage of fully vaccinated persons (i.e. received all recommended doses of an FDA-authorized COVID-19 vaccine) will develop symptomatic or asymptomatic infections with SARS-CoV-2, the virus that causes COVID-19 (2-8).

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.

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.

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.

The Foodborne Diseases Active Surveillance Network (FoodNet) conducts population-based surveillance for Campylobacter infection. For 2010 through 2015, we compared patients with Campylobacter jejuni with patients with infections caused by other Campylobacter species. Campylobacter coli patients were more often >40 years of age (OR = 1.4), Asian (OR = 2.3), or Black (OR = 1.7), and more likely to live in an urban area (OR = 1.2), report international travel (OR = 1.5), and have infection in autumn or winter (OR = 1.2). Campylobacter upsaliensis patients were more likely female (OR = 1.6), Hispanic (OR = 1.6), have a blood isolate (OR = 2.8), and have an infection in autumn or winter (OR = 1.7). Campylobacter lari patients were more likely to be >40 years of age (OR = 2.9) and have an infection in autumn or winter (OR = 1.7). Campylobacter fetus patients were more likely male (OR = 3.1), hospitalized (OR = 3.5), and have a blood isolate (OR = 44.1). International travel was associated with antimicrobial-resistant C. jejuni (OR = 12.5) and C. coli (OR = 12) infections. Species-level data are useful in understanding epidemiology, sources, and resistance of 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.

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 approximately 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.

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 SalmonellaTyphi and Paratyphi A isolates sent for testing by participating public health laboratories to CDC'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 US is primarily associated with travel to southern Asia and increasing resistance is adding to treatment challenges. A bivalent typhoid and paratyphoid vaccine is needed.

Although rare, typhoid fever cases acquired in the United States continue to be reported. Detection and investigation of outbreaks in these domestically acquired cases offer opportunities to identify chronic carriers. We searched surveillance and laboratory databases for domestically acquired typhoid fever cases, used a space-time scan statistic to identify clusters, and classified clusters as outbreaks or non-outbreaks. From 1999 to 2010, domestically acquired cases accounted for 18% of 3373 reported typhoid fever cases; their isolates were less often multidrug-resistant (2% vs. 15%) compared to isolates from travel-associated cases. We identified 28 outbreaks and two possible outbreaks within 45 space-time clusters of 2 domestically acquired cases, including three outbreaks involving 2 molecular subtypes. The approach detected seven of the ten outbreaks published in the literature or reported to CDC. Although this approach did not definitively identify any previously unrecognized outbreaks, it showed the potential to detect outbreaks of typhoid fever that may escape detection by routine analysis of surveillance data. Sixteen outbreaks had been linked to a carrier. Every case of typhoid fever acquired in a non-endemic country warrants thorough investigation. Space-time scan statistics, together with shoe-leather epidemiology and molecular subtyping, may improve outbreak detection.

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.

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 isolated from humans were also tested. For each isolate, minimum inhibitory concentrations (MICs) to azithromycin and 15 other antimicrobial agents were determined by broth microdilution. Among the non-Typhi Salmonella isolates, azithromycin MICs among human isolates ranged from 1-32 mcg/mL whereas the MICs among the animal and retail meat isolates ranged from 2-16 mcg/mL and 4-16 mcg/mL, respectively. Among Salmonella ser. Typhi isolates the azithromycin MICs ranged from 4-16 mcg/mL. The highest MIC observed in the present study was 32 mug/mL and was detected in three isolates from humans belonging to serotypes Kentucky, Montevideo and Paratyphi A. Based on our findings, we propose an epidemiological cut-off value (ECOFF) of wild type ≤ 16 mcg/mL for azithromycin and Salmonella. The susceptibility data provided could be used in combination with clinical outcome data to determine tentative clinical breakpoints for azithromycin and Salmonella enterica.

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.

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 1996-2007. We described antimicrobial resistance among invasive strains by serogroup and serotype. Of the 19,302 NTS, 17,804 (92.2%) were from stool or blood. Of these, 1,050 (5.9%) were bloodstream isolates. The median age (range) of patients with and without bacteremia was 36 (0, 97) years and 20 (0, 105) years, respectively (p<0.001). Males (OR 1.21, 95% CI 1.06, 1.38) and those aged ≥65 years were at greater risk for invasive disease. Enteritidis, Typhimurium, and Heidelberg were the most common serotypes isolated from blood; 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.

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 beta-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 beta-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 beta-lactamase genes could be detected in 139 (80.8%) isolates. The most prevalent resistance mechanism detected was the AmpC beta-lactamase gene bla(CMY.) Other beta-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 beta-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.

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, beta-lactam/beta-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.

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 mug/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.

CONTEXT: Typhoid fever in the United States has increasingly been due to infection with antimicrobial-resistant Salmonella ser Typhi. National surveillance for typhoid fever can inform prevention and treatment recommendations. OBJECTIVE: To assess trends in infections with antimicrobial-resistant S. Typhi. DESIGN: Cross-sectional, laboratory-based surveillance study. SETTING AND PARTICIPANTS: We reviewed data from 1999-2006 for 1902 persons with typhoid fever who had epidemiologic information submitted to the Centers for Disease Control and Prevention (CDC) and 2016 S. Typhi isolates sent by participating public health laboratories to the National Antimicrobial Resistance Monitoring System Laboratory at the CDC for antimicrobial susceptibility testing. MAIN OUTCOME MEASURES: Proportion of S. Typhi isolates demonstrating resistance to 14 antimicrobial agents and patient risk factors for antimicrobial-resistant infections. RESULTS: Patient median age was 22 years (range, <1-90 years); 1295 (73%) were hospitalized and 3 (0.2%) died. Foreign travel within 30 days of illness was reported by 1439 (79%). Only 58 travelers (5%) had received typhoid vaccine. Two hundred seventy-two (13%) of 2016 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant S. Typhi [MDRST]); 758 (38%) were resistant to nalidixic acid (nalidixic acid-resistant S. Typhi [NARST]) and 734 NARST isolates (97%) had decreased susceptibility to ciprofloxacin. The proportion of NARST increased from 19% in 1999 to 54% in 2006. Five ciprofloxacin-resistant isolates were identified. Patients with resistant infections were more likely to report travel to the Indian subcontinent: 85% of patients infected with MDRST and 94% with NARST traveled to the Indian subcontinent, while 44% of those with susceptible infections did (MDRST odds ratio, 7.5; 95% confidence interval, 4.1-13.8; NARST odds ratio, 20.4; 95% confidence interval, 12.4-33.9). CONCLUSION: Infection with antimicrobial-resistant S. Typhi strains among US patients with typhoid fever is associated with travel to the Indian subcontinent, and an increasing proportion of these infections are due to S. Typhi strains with decreased susceptibility to fluoroquinolones.