The Centers for Disease Control and Prevention (CDC) has issued an advisory on an increase in extensively drug-resistant (XDR) Shigella infections in the United States.
In a health advisory posted late last week by the CDC's Health Alert Network (HAN), the agency said 5% of Shigella infections (shigellosis) reported in 2022 were caused by XDR strains, up from 0% in 2015 (see graph below). Those strains are resistant to commonly recommended empiric and alternative antibiotics.
Shigellosis is a gastrointestinal condition caused by one of the four species of Shigella bacteria: Shigella sonnei, S flexneri, S boydii, or S dysenteriae. Symptoms range from mild diarrhea to severe dysentery. Most cases are self-limiting, but antibiotics are frequently used to treat more severe symptoms and reduce shedding, which can help limit transmission.
The CDC says that, in addition to limiting the treatment options for patients, XDR Shigella strains are a concern because they can spread antimicrobial resistance genes to other enteric bacteria.
"Given these potentially serious public health concerns, CDC asks healthcare professionals to be vigilant about suspecting and reporting cases of XDR Shigella infection to their local or state health department and educating patients and communities at increased risk about prevention and transmission," the agency said.
Demographic shift to at-risk adults
The HAN alert comes on the heels of a spate of reports about XDR Shigella outbreaks in Europe, the United Kingdom, and the United States. Many of these outbreaks have occurred among networks of men who have sex with men (MSM), with transmission occurring through sexual activity.
In January, researchers from the University of Washington School of Medicine and the Seattle and King County public health department described an ongoing outbreak involving multiple XDR strains in Seattle that began in 2017 and has spread among both MSM and the homeless.
CDC officials say the alert was prompted by multiple reports of XDR Shigella from state health departments around the country, as well as questions from infectious disease clinicians about how to treat these infections.
"The thing that really pushed us over the top was receiving these repeated inquiries from our state health partners and clinicians saying 'we don't know what to do with what we're seeing,' " CDC medical epidemiologist Louise Francois Watkins, MD, MPH, told CIDRAP News. "It just felt like maybe this is the time to put it on the map."
Shigellosis is commonly associated with exposure to food or water that has been contaminated by human feces and is highly contagious, spreading easily in settings with overcrowding and poor sanitation. It causes an estimated 450,000 infections in the United States each year.
"Shigella bacteria are so easily transmitted, and they have such a low infectious dose, that outbreaks are common, and you typically see this among people in close-contact settings or crowded conditions," said CDC medical officer Naeemah Logan, MD.
The CDC notes that historically, drug-susceptible Shigella has predominantly affected young children (ages 1 through 4) in the United States, with spread commonly seen in daycare settings among children who haven't been toilet-trained.
But that appears to be changing. Perhaps because of the COVID-19 pandemic, shigellosis cases in US children have declined over the past few years. At the same time, the agency says it has seen an increase in drug-resistant Shigella infections in vulnerable adults, especially MSM but also the homeless, international travelers, and people with HIV.
"It does seem that we've seen a demographic shift towards more cases that are occurring among adult men," Francois Watkins said. And while the CDC doesn't routinely collect sexual history when it receives case reports, Francois Watkins noted that in specific outbreak investigations, male patients have been reporting new sexual partners.
More than 230 XDR cases
Those trends are reflected in the data from the HAN health advisory. From 2015 to Jan 22 of this year, the CDC says it has received reports of 239 XDR Shigella isolates, mainly S sonnei (66%) and S flexneri (34%).
The median age of case-patients was 42 years, and of the 232 patients with available information, 82% were men. Of the 41 patients who answered questions about sexual activity, 88% reported male-to-male sexual contact.
It's definitely the tip of the iceberg
But those are just the cases that have been identified through surveillance. Not everyone with shigellosis goes to the doctor, and those who do don't always get stool cultures, which then need to be forwarded to state health departments for further analysis, including whole-genome sequencing.
"It's definitely the tip of the iceberg," said Francois Watkins. "You need a lot of things to happen for a case to enter our surveillance system."
And because Shigella is so easily transmissible, there is concern about wider spread of XDR strains beyond people in vulnerable populations, who may work in the food service industry or healthcare or take care of young children or the elderly, Francois Watkins added.
"This is not a disease that anyone is going to be completely safe from just because of the nature of the way it can spread through different modes of transmission," she said.
Messages for clinicians
The CDC is urging clinicians to consider shigellosis in the diagnosis of acute diarrhea, especially in higher-risk groups such as MSM, the homeless, international travelers, people who have HIV, and young children. They also want clinicians to ask about relevant exposures and social history and to obtain cultures for further analysis.
"Despite the public health concern, there may be a low awareness of shigellosis as a sexually transmitted infection among healthcare providers," Logan said. "We want to try and bridge that gap."
The HAN health advisory notes that, because there are no data from clinical studies of XDR Shigella treatment, the CDC does not have recommendations for optimal antibiotic treatment. XDR strains can be resistant to both the standard empiric treatments—azithromycin, ciprofloxacin, or ceftriaxone—and alternative options such as trimethoprim-sulfamethoxazole and ampicillin. But the agency wants clinicians to know that with the increase in XDR infections, they need to be careful about which antibiotic they prescribe.
We want to make them more aware of the important role they play in antibiotic stewardship.
"We want to make them more aware of the important role they play in antibiotic stewardship and curbing this concerning increase in XDR shigellosis," said Logan.
"Part of our messaging in this health alert is that we want healthcare professionals to be aware that if you try to make a guess about which antibiotic is going to work for Shigella, the odds are really increasing that you're going to guess wrong," Francois Watkins said.
