Non-typhoidal Salmonella cause an estimated 1.4 million human illnesses, 26,000 hospitalizations and 400 deaths annually in the United States. Approximately 11% of these infections are attributed to animal contact. Reptiles and amphibians are known sources of salmonellosis; young children (aged <5 years) are disproportionately affected by reptile- and amphibian-associated salmonellosis (RAAS) outbreaks. We describe multistate RAAS outbreaks to characterize illnesses and inform prevention efforts. RAAS outbreaks were defined as ≥2 culture-confirmed human Salmonella infections with similar pulsed-field gel electrophoresis patterns and epidemiologic, laboratory or traceback evidence linking them to a common reptile/amphibian exposure. Data sources included the Animal Contact Outbreak Surveillance System; CDC Outbreak Response and Prevention Branch's outbreak management database; PulseNet, the national molecular subtyping network for foodborne disease surveillance in the United States; and the National Antimicrobial Resistance Monitoring System. Twenty-six RAAS outbreaks were reported during 2009-2018, resulting in 1465 illnesses and 306 hospitalizations. The outbreaks were associated with turtles (19), lizards (5), snakes (1) and frogs (1). Sixteen (61.5%) outbreaks were linked to small turtles (<4 inches), resulting in 914 illnesses. Forty-nine percent of outbreak-associated patients were aged <5 years. Of 362 patients/caregivers interviewed, 111 (30.7%) were aware that reptiles/amphibians can carry Salmonella. Among 267 patient isolates with antimicrobial susceptibility information, 20 (7.5%) were non-susceptible to ≥1 antibiotic used to treat human salmonellosis. RAAS outbreaks result in considerable morbidity, particularly among young children. Illnesses linked to small turtles are preventable through education, targeted outreach to caregivers and paediatricians, and when appropriate, enforcement. Historically, individual states and jurisdictions have enforced existing or promulgated new authorities to address outbreaks. Preventing future RAAS outbreaks requires addressing challenges related to the illegal sale/distribution of small turtles; and for legal reptile sales, providing information on RAAS risk to consumers at point of sale to support informed pet ownership decisions.

In 2017, state health departments notified the Centers for Disease Control and Prevention about 4 patients with shigellosis who experienced persistent illness after treatment with oral third-generation cephalosporins. Given increasing antibiotic resistance among Shigella, these cases highlight the need to evaluate the efficacy of oral cephalosporins for shigellosis.

Abstract Background Multidrug-resistant (MDR) Shigella sonnei infections are a serious public health threat, and outbreaks are common among men who have sex with men (MSM). In February 2020, Australia’s Department of Health notified CDC of extensively drug-resistant (XDR) S. sonnei in 2 Australian residents linked to a cruise that departed from Florida. We describe an international outbreak of XDR S. sonnei and report on trends in MDR among S. sonnei in the United States. Methods Health departments (HDs) submit every 20th Shigella isolate to CDC’s National Antimicrobial Resistance Monitoring System (NARMS) laboratory for susceptibility testing. We defined MDR as decreased susceptibility to azithromycin (MIC ≥32 µg/mL) with resistance to ampicillin, ciprofloxacin, and cotrimoxazole, and XDR as MDR with additional resistance to ceftriaxone. We used PulseNet, the national subtyping network for enteric disease surveillance, to identify US isolates related to the Australian XDR isolates by short-read whole genome sequencing. We screened these isolates for resistance determinants (ResFinder v3.0) and plasmid replicons (PlasmidFinder) and obtained patient histories from HDs. We used long-read sequencing to generate closed plasmid sequences for 2 XDR isolates. Results NARMS tested 2,781 S. sonnei surveillance isolates during 2011–2018; 80 (2.9%) were MDR, including 1 (0.04%) that was XDR. MDR isolates were from men (87%), women (9%), and children (4%). MDR increased from 0% in 2011 to 15.3% in 2018 (Figure). In 2020, we identified XDR isolates from 3 US residents on the same cruise as the Australians. The US residents were 41–42 year-old men; 2 with available information were MSM. The US and Australian isolates were highly related (0–1 alleles). Short-read sequence data from all 3 US isolates mapped to the blaCTX-M-27 harboring IncFII plasmids from the 2 Australian isolates with >99% nucleotide identity. blaCTX-M-27 genes confer ceftriaxone resistance. Increase in Percentage of Shigella sonnei Isolates with Multidrug Resistance* in the United States, 2011–2018† Conclusion MDR S. sonnei is increasing and is most often identified among men. XDR S. sonnei infections are emerging and are resistant to all recommended antibiotics, making them difficult to treat without IV antibiotics. This outbreak illustrates the alarming capacity for XDR S. sonnei to disseminate globally among at-risk populations, such as MSM. Disclosures All Authors: No reported disclosures

A multidrug-resistant Salmonella enterica serotype Anatum strain reported in Taiwan was isolated in the United States from patients and from seafood imported from Asia. Isolates harbored 11 resistance determinants, including quinolone and inducible cephalosporin resistance genes. Most patients had traveled to Asia. These findings underscore the need for global One Health resistance surveillance.

A qepA8 + Shigella flexneri was cultured from the stool of a traveler returning from India and East Asia. This chromosomally encoded qepA variant, has a six-base insertion, and may have been mobilized as part of a complex IS 1- mediated composite transposon including catA1, aadA1 , and bla OXA-1. In laboratory E. coli , qepA8 alone only conferred decreased ciprofloxacin susceptibility; however, it may work in combination with additional mechanisms to confer clinical resistance.

Nontyphoidal Salmonella (NTS) causes an estimated 1.2 million illnesses, 23,000 hospitalizations, and 450 deaths each year in the United States. Decreased susceptibility to ciprofloxacin (DSC) has historically been associated with chromosomal mutations of the quinolone resistance determining region (QRDR), but plasmid-mediated quinolone resistance (PMQR) genes are increasing. To investigate DSC among Salmonella enterica serotype Newport strains, we examined 40 isolates from 1996 to 2016 with DSC. Thirty isolates (71%) contained the PMQR gene qnrB and eight isolates (19%) contained a QRDR.

Invasive Salmonella infections in adults are commonly treated with fluoroquinolones, a critically important antimicrobial class. Historically, quinolone resistance was the result of chromosomal mutations, but plasmid-mediated quinolone resistance (PMQR) has emerged and is increasingly being reported in Enterobacteriaceae worldwide. PMQR may facilitate the spread of quinolone resistance, lead to higher-level quinolone resistance, and make infections harder to treat. To better understand the epidemiology of PMQR in non-typhoidal Salmonella causing human infections in the United States, we looked at trends in quinolone resistance among isolates submitted to the Centers for Disease Control and Prevention. We reviewed demographic, exposure and outcome information for patients with isolates having a PMQR-associated phenotype during 2008-2014 and tested isolates for quinolone resistance mechanisms. We found that PMQR is emerging among non-typhoidal Salmonella causing human infections in the United States and that international travel, reptile and amphibian exposure, and food are likely sources of human infection.

Abstract Background Shigella spp. cause ~500,000 illnesses in the United States annually. Antibiotics are recommended for immunocompromised patients and shorten the duration of illness, thus limiting spread. First-line treatments include ciprofloxacin (CIP) and azithromycin (AZM). CIP resistance is a growing problem in the United States; decreased susceptibility to AZM (DSA) has been reported globally, particularly among men who have sex with men (MSM). We reviewed National Antimicrobial Resistance Monitoring System (NARMS) data to determine DSA trends among Shigella isolates in the United States. Methods Health departments nationwide forward every 20th Shigella isolate to CDC NARMS for antimicrobial susceptibility testing using broth microdilution. We defined CIP resistance using CLSI clinical breakpoints and DSA using epidemiological cutoff values where available. We performed whole genome sequencing on isolates from 2016 and screened the sequences for resistance determinants using ResFinder 3.0. Results To date, we have tested 3,044 Shigella isolates collected during 2011–2017. Overall, 264 isolates (9%) had DSA, increasing from 3% in 2011 to 23% in 2017; 41 (16%) were also CIP resistant. The odds of DSA increased by 1.5 (95% confidence interval [CI] 1.4–1.6) annually. DSA was more common among adult males (OR 21.2, CI 14.9–30.3), in isolates from the West census region (OR 2.4, CI 1.8–3.2), and in S. flexneri (OR 8.2, CI 6.3–10.7). Of 543 sequenced isolates, 52 (10%) had DSA; of these, 31 (60%) contained both mph(A) and erm(B) genes, 17 (33%) contained mph(A) only, and 4 (8%) had no identified macrolide-resistance mechanism. Conclusions In 2017, nearly 1 in 4 Shigella isolates tested had DSA, a 7-fold increase since 2011. This rapid rise in DSA parallels that seen in other countries, where resistance to other clinically relevant drugs is high and macrolides are no longer useful as empiric treatment. The increased risk of DSA in adult males is consistent with previous reports of DSA Shigella in MSM. The resistance genes observed are typically plasmid-mediated and can be transferred to other bacteria. Public health strategies to mitigate the spread of resistant Shigella should include antibiotic stewardship and novel approaches for sexually transmitted infection prevention in MSM. Disclosures All authors: No reported disclosures.

Newport is the third most common Salmonella enterica serotype identified among the estimated 1.2 million human salmonellosis infections occurring annually in the United States. Risk factors for infection and food items implicated in outbreaks vary by antimicrobial resistance pattern. We conducted a descriptive analysis of data from four enteric disease surveillance systems capturing information on incidence, demographics, seasonality, geographic distribution, outbreaks, and antimicrobial resistance of Newport infections over a 10-year period from 2004 through 2013. Incidence increased through 2010, then declined to rates similar to those in the early years of the study. Incidence was highest in the South and among children <5 years old. Among isolates submitted for antimicrobial susceptibility testing, 88% were susceptible to all antimicrobials tested (pansusceptible) and 8% were resistant to at least seven agents, including ceftriaxone. Rates of pansusceptible isolates were also highest in the South and among young children, particularly in 2010. Pansusceptible strains of Newport have been associated with produce items and environmental sources, such as creek water and sediment. However, the role of environmental transmission of Newport in human illness is unclear. Efforts to reduce produce contamination through targeted legislation, as well as collaborative efforts to identify sources of contamination in agricultural regions, are underway.

Antimicrobial resistance among nontyphoidal Salmonella (NTS) is a serious public health threat. Resistance to azithromycin, a clinically-important antimicrobial, has historically been rare in NTS in the United States but is often plasmid-mediated. We evaluated trends and assessed characteristics of national NTS isolates with azithromycin resistance. In 2011–2016, US health departments submitted every 20th NTS isolate for surveillance and additional outbreak isolates to CDC’s National Antimicrobial Resistance Monitoring System laboratory, where they were tested for antimicrobial susceptibility by broth microdilution to 14 drugs, including azithromycin. Resistance to azithromycin was defined by a minimum inhibitory concentration of ≥32 µg/mL based on the current Clinical and Laboratory Standards Institute’s investigational breakpoint for Salmonella Typhi. A subset of isolates underwent whole genome sequencing; sequences were screened for the presence of resistance determinants. Epidemiological characteristics were reviewed when available. We identified 29 NTS isolates with azithromycin resistance representing 22 different serotypes from 19 states. The prevalence of azithromycin resistance among surveillance isolates increased from 1.4 per 1000 isolates tested in 2011–2014 to 3.7 per 1,000 in 2015–2016 (P = 0.014). In addition to azithromycin resistance, most isolates were multidrug resistant; 16 (55%) were resistant to agents from ≥5 antimicrobial classes. Of 16 sequenced isolates with resistance genes detected, 13 (81%) had mphA and 2 (13%) had mphE. Median patient age was 45 years (interquartile range 21–61.5; n = 29); 13 (46%; n = 28) were male. Of 15 patients with travel histories, 5 (33%) traveled to Asia, 2 (13%) traveled to Latin America, and 1 (7%) traveled to Europe prior to illness onset. Azithromycin resistance among NTS is increasing in the United States, though it remains rare. The rise is associated with the emergence of plasmid-mediated macrolide resistance genes mphA and mphE, raising concern for spread of resistance among bacteria. Resistance determinants may enter the USA via international travelers, while frequent clinical use of azithromycin may contribute to selective pressure domestically. All authors: No reported disclosures.

BACKGROUNDCeftriaxone resistance in Salmonella is a serious public health threat. Ceftriaxone is commonly used to treat severe Salmonella infections, especially in children. Identifying the sources and drivers of ceftriaxone resistance among nontyphoidal Salmonella is crucial.MATERIALS AND METHODSThe National Antimicrobial Resistance Monitoring System (NARMS) tracks antimicrobial resistance in foodborne and other enteric bacteria from humans, retail meats, and food animals. We examined NARMS data reported during 1996-2013 to characterize ceftriaxone-resistant Salmonella infections in humans. We used Spearman rank correlation to examine the relationships between the annual percentage of ceftriaxone resistance among Salmonella isolates from humans with isolates from retail meats and food animals.RESULTSA total of 978 (2.9%) of 34,100 nontyphoidal Salmonella isolates from humans were resistant to ceftriaxone. Many (40%) ceftriaxone-resistant isolates were from children younger than 18 years. Most ceftriaxone-resistant isolates were one of three serotypes: Newport (40%), Typhimurium (26%), or Heidelberg (12%). All were resistant to other antimicrobials, and resistance varied by serotype. We found statistically significant correlations in ceftriaxone resistance between human and ground beef Newport isolates (r = 0.83), between human and cattle Typhimurium isolates (r = 0.57), between human and chicken Heidelberg isolates (r = 0.65), and between human and turkey Heidelberg isolates (r = 0.67).CONCLUSIONSCeftriaxone resistance among Salmonella Newport, Typhimurium, and Heidelberg isolates from humans strongly correlates with ceftriaxone resistance in isolates from ground beef, cattle, and poultry, respectively. These findings support other lines of evidence that food animals are important reservoirs of ceftriaxone-resistant Salmonella that cause human illness in the United States.

Drug-resistant bacterial infections pose a serious and growing public health threat globally. In this review, we describe the role of the National Antimicrobial Resistance Monitoring System (NARMS) in providing data that help address the resistance problem and show how such a program can have broad positive impacts on public health. NARMS was formed two decades ago to help assess the consequences to human health arising from the use of antimicrobial drugs in food animal production in the United States. A collaboration among the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the United States Department of Agriculture, and state and local health departments, NARMS uses an integrated "One Health" approach to monitor antimicrobial resistance in enteric bacteria from humans, retail meat, and food animals. NARMS has adapted to changing needs and threats by expanding surveillance catchment areas, examining new isolate sources, adding bacteria, adjusting sampling schemes, and modifying antimicrobial agents tested. NARMS data are not only essential for ensuring that antimicrobial drugs approved for food animals are used in ways that are safe for human health but they also help address broader food safety priorities. NARMS surveillance, applied research studies, and outbreak isolate testing provide data on the emergence of drug-resistant enteric bacteria; genetic mechanisms underlying resistance; movement of bacterial populations among humans, food, and food animals; and sources and outcomes of resistant and susceptible infections. These data can be used to guide and evaluate the impact of science-based policies, regulatory actions, antimicrobial stewardship initiatives, and other public health efforts aimed at preserving drug effectiveness, improving patient outcomes, and preventing infections. Many improvements have been made to NARMS over time and the program will continue to adapt to address emerging resistance threats, changes in clinical diagnostic practices, and new technologies, such as whole genome sequencing.

BACKGROUND:Salmonella causes an estimated 100 000 antimicrobial-resistant infections annually in the United States. Salmonella antimicrobial resistance may result in bacteremia and poor outcomes. We describe antimicrobial resistance among nontyphoidal Salmonella blood isolates, using data from the National Antimicrobial Resistance Monitoring System. METHODS:Human nontyphoidal Salmonella isolates from 2003 to 2013 were classified as fully susceptible, resistant to ≥1 antimicrobial agent, or resistant to a first-line agent. Logistic regression was used to compare resistance patterns, serotypes, and patient characteristics for Salmonella isolated from blood versus stool and to determine resistance trends over time. RESULTS:Approximately 20% of blood isolates had antimicrobial resistance to a first-line treatment agent. Bacteremia was associated with male sex, age ≥65 years, and specific serotypes. Blood isolates were more likely to be resistant to ≥1 agent for serotypes Enteritidis, Javiana, Panama, and Typhimurium. Blood isolates were most commonly resistant to tetracycline (19%), and more likely resistant to a first-line agent (odds ratio, 1.81; 95% confidence interval, 1.56-2.11) than stool isolates. Ceftriaxone resistance increased in blood isolates from 2003 to 2013 (odd ratio, 1.12; 95% confidence interval, 1.02-1.22). CONCLUSIONS:Resistance to first-line treatment agents in patients with Salmonella bacteremia is a concern for public health and for informing clinical decisions. Judicious antimicrobial use is crucial to limit resistance.

We found a strong association between nalidixic acid-resistant Salmonella enterica serotype Enteritidis infections in the United States and recent international travel by linking Salmonella Enteritidis data from the National Antimicrobial Resistance Monitoring System and the Foodborne Diseases Active Surveillance Network.

In a recently published article, Phillips et al. 1 claim that they 'attempt to draw out facts among much misinformation'.In actuality, their article is fraught with inaccurate and misleading citations and other errors.Moreover, their 'review' article is far from an unbiased scientific review of the literature, as the authors appear to report only those studies and findings which they interpret as being supportive of their opinions.Due to word and reference limitations, our comments address only a portion of the authors' discussion of Campylobacter.In their efforts to persuade readers that chicken is not a risk factor for human Campylobacter infection (despite the multitude of evidence demonstrating that it is), Phillips et al. 1 state 'Once venue is taken into account, chicken is no longer a risk factor (Tables 2 and3)'.Phillips et al. 1 incorrectly cite an article by Engberg et al. 2 for this statement.In fact, Engberg et al. 2 state, 'Campylobacteriosis is primarily a zoonosis.Evidence to indicate that fresh raw meat, especially poultry, is a major source of infection is ample. ..'. Phillips et al. 1 also incorrectly state that Table 2, which lists odds ratios for 'protective factors', is based on Neimann 3 and Engberg et al. 2 The Engberg et al. 2 article neither refers to protective factors nor presents odds ratios, but it does state, 'Fluoroquinolone resistance in Campylobacter from food animals is now recognized as an emerging public health problem'.Furthermore, Tables 2 and3 incorrectly state in their titles that the data they provide are for Campylobacter jejuni, when in fact, the references and studies upon which the tables are based are not limited to C. jejuni.With regard to the human health consequences of resistance in Campylobacter, Phillips et al. 1 misrepresent one study and omit the findings of three pertinent ones.Phillips et al. 1 state 'Marano et al. reported a 4 day decrease in the duration of diarrhoea (from 12 to 8 days) for patients infected with fluoroquinolone-resistant strains treated with ciprofloxacin (but paradoxically no decrease for susceptible strains-6 days for both treated and untreated patients)'.Marano et al. 4 actually reported that patients with ciprofloxacin-resistant Campylobacter infections had a longer duration of diarrhoea than those with sus-

There is accumulating evidence that the use of antimicrobials in food-producing animals has adverse human health consequences. The use of antibiotics in food animals selects for resistant pathogens and resistance genes that may be transferred to humans through the consumption or handling of foods of animal origin. Recent studies have demonstrated that antimicrobial-resistance among foodborne bacteria may cause excess cases of illness, prolonged duration of illness, and increased rates of bacteremia, hospitalization, and death. The continued availability of safe and effective antimicrobials for humans and animals depends upon the responsible use of these products.

Two privately owned domestic rabbits (Oryctolagus cuniculus) in Maryland were found to be infected with the raccoon variant of the rabies virus in 1998. Both rabbits had an acute onset of anorexia and paralysis or paresis of the left forelimb; 1 also developed head tremors and a head tilt. One of the rabbits became ill 25 days after being attacked by a raccoon (Procyon lotor) and was euthanatized 3 days after onset of illness. The other rabbit, which was housed in an outdoor hutch, died 4 days after onset of clinical signs; the source of infection in that rabbit remains unknown. Currently, there is not a rabies vaccine approved for use in rabbits; thus, the only way to prevent the infection in rabbits is to prevent exposure. Veterinarians in rabies-enzootic areas should be familiar with the clinical signs of rabies in rabbits and should caution rabbit owners about the need to protect their pets from contact with wildlife.

An outbreak of dengue fever occurred among a small group of Maryland and Pennsylvania residents following a trip to the British Virgin Islands in January 1996. Dengue fever is a mosquito-borne viral illness that occurs primarily in tropical urban areas. Most dengue infections are benign and self-limited, but some produce severe and fatal hemorrhagic disease. Although dengue is not endemic in the continental United States, travelers may acquire the infection during visits to the tropics. Physicians should consider dengue in the differential diagnosis of a patient with a febrile illness and a history of recent travel to a tropical area. Travelers to endemic areas should be advised to take precautions to prevent mosquito bites.