Salmonella Studies: New Drug-Resistant Strain, Effective Control Measure

Salmonellosis continues to be a topical public health threat for Americans, as highlighted by 2 new studies featured in the December 2018 issue of Emerging Infectious Diseases, the monthly peer-reviewed public health journal of the US Centers for Disease Control and Prevention (CDC).

Allison C. Brown, PhD, MPH, from the CDC, Atlanta, Georgia, and colleagues share data about a new strain of multidrug-resistant Salmonella Infantis that has recently emerged in the United States, linked with retail chicken meat. “This strain possesses clinically important resistance associated with higher hospitalization rates,” they stressed.

Cindy R. Friedman, MD, also from the CDC, explained why this finding is so concerning. “This multidrug-resistance eliminates many of the recommended treatment options for the management of severe Salmonella infection, such as ampicillin, trimethoprim-sulfamethoxazole, ceftriaxone, and ciprofloxacin,” she told Contagion®.

In contrast, however, Melanie Firestone, MPH, a PhD candidate from the University of Minnesota School of Public Health, Minneapolis, and colleagues report data from a different study, highlighting 1 approach that proved beneficial to reducing rates of foodborne Salmonella infections.

“Our research looked at the public health impact of New York City's letter grade program,” she told Contagion®. “We found that there was a significant decline in Salmonella infections in New York City after the letter grade program was implemented.”

Salmonella infection is one of the most important causes of bacterial foodborne illness in the United States. This frequently involves Salmonella Infantis (Salmonella enterica serotype Infantis), the incidence of which has risen by 60% in the past decade. Poultry and pigs represent the main animal reservoirs of this serovar.

Although salmonellosis typically causes self-limiting episodes of gastroenteritis, severe cases, especially in patients who have a high risk for invasive disease, require antibiotic therapy.

Extended-spectrum β-lactamases (ESBLs) are bacterial enzymes that confer resistance to clinically useful third-generation cephalosporins that are often used in these invasive cases. Of the ESBLs, the CTX-M family has become one of the most important families of these enzymes worldwide.

Although ESBL-producing Salmonellae are rare in the United States, a CTX-M-65-containing Salmonella Infantis strain was isolated from retail chicken meat in 2014.

Dr. Brown and colleagues showed this isolate to have a unique DNA fingerprint, characterized as pattern 787.

The investigators also examined 34 isolates with this pattern that were collected from human surveillance and associated metadata during 2012 through 2015. They found that these clinical isolates were genetically related to the original isolate obtained from retail chicken in 2014.

In addition, 29 (85%) of the clinical isolates had resistance phenotypes consistent with ESBL-conferred resistance to ceftriaxone, ceftiofur, and ampicillin, and also contained the blaCTX-M-65 gene with multiple additional resistance genes on 1 plasmid.

The investigators had outcome data for 18 of the patients infected with CTX-M-65 Infantis, showing that 8 (44%) were hospitalized. This hospitalization rate was 50% higher than for patients infected with all Salmonella Infantis strains or other common Salmonella serotypes, for whom the rate was 29%.

They also found that 12 (63%) patients with CTX-M-65 Infantis infections had traveled internationally in the 7 days before they developed symptoms.

“All reported travel to South America, 10 to Peru, and 2 to Ecuador,” they wrote. In contrast, travel was less common among patients infected with all Salmonella Infantis strains (7%, P<.01) and with other common serotypes (8%, P<.01). “This finding is consistent with those of other studies that found foreign travel to be a risk factor for CTX-M—type ESBLs,” the authors said.

Because more than one-third of CTX-M-65 Infantis-infected patients had no history of recent international travel, they were likely exposed via a domestic source. CTX-M genes have been linked with poultry, particularly broiler chickens, and reports have indicated that this strain was present in domestic food processing plants at the end of study period (2014—2015). However, because extensive sampling of poultry plants did not occur before 2014, it remains unknown how and when this new strain entered poultry stock in the United States.

Given the multidrug resistant profile of CTX-M-65 Infantis, the potential for the gene to be transmitted to other bacteria, high hospitalization rates among infected persons, and evidence of this strain in domestic poultry, Dr. Friedman told Contagion® that action is needed to prevent further dissemination in poultry flocks in the United States, and to decrease opportunities for it to spread to other food animals and to people.

“Enhanced surveillance and additional studies in humans and food animals may help pinpoint the sources of infection for implementation of prevention and control measures,” Dr Brown and colleagues conclude. “Meanwhile, travelers and health care providers should be aware of the risks and implications of infection with this strain, including the potential for antimicrobial treatment failure.”

And, for patients who require treatment, Dr. Friedman encourages healthcare providers to order a culture with antimicrobial susceptibility testing, because some common first-line antibiotics may not work.

“Since this study was reported, there have been further links between multidrug-resistant Salmonella Infantis and chicken exposure,” she added. “Therefore, consumers should remember to follow safe handling and cooking guidelines, such as washing hands before and after handling chicken and cooking chicken to an internal temperature of 165&#730;F.”

According to Ms. Firestone and colleagues, restaurants also play a key role in the epidemiology of foodborne Salmonella infections. This is becoming more evident as consumers continue to increasingly favor eating food prepared at restaurants, rather than at home. Indeed, “in 2015, 60% of foodborne illness outbreaks were associated with restaurants,” they wrote.

“Restaurants are frequent settings for transmission of Salmonella infections because Salmonella can take advantage of many transmission pathways in restaurants,” Ms. Firestone told Contagion®.

Although reducing Salmonella infections is a Healthy People 2020 objective, she noted that rates of Salmonella infection in the United States have not been declining in the past 20 years, despite efforts to improve food safety.

Since 2010, New York City has required restaurants to post letter grades in their windows that correspond to scores received from sanitary inspections by the Department of Health and Mental Hygiene.

“Letter grades for restaurant inspections promote transparency by triggering a feedback loop that leads to improved sanitary conditions,” Ms. Firestone said. “By improving sanitary conditions, an expected outcome is a reduction in risk of illness.”

And this is exactly what the results of this study showed.

“Compared to the rest of the state, we found that Salmonella infections declined an average of 5.3% per year in New York City after the letter grade program was implemented, compared to the period before implementation,” Ms. Firestone said.

“This study demonstrates the usefulness of Salmonella surveillance data for evaluating the effectiveness of food safety policies and programs, and in identifying opportunities for prevention,” she noted.

Although the letter grading approach used in New York City provides a valuable case study of the beneficial impact of such programs for restaurant inspections, Ms. Firestone also emphasized the need for additional studies to better understand which factors contribute the most to declines in infections.

“As the use of culture-independent diagnostic tests increases,” she explained. “More cases of Salmonella infection will likely be reported, which will provide more data and possibly more ways to use these data to guide prevention efforts.”

Dr. Parry, a board-certified veterinary pathologist, graduated from the University of Liverpool in 1997. After 13 years in academia, she founded Midwest Veterinary Pathology, LLC, where she now works as a private consultant. Dr. Parry writes regularly for veterinary organizations and publications.