Cases of extensively drug-resistant (XDR) Shigella, for which no approved treatment is available, increased significantly between 2011 and 2023, based on data from approximately 17,000 isolates.

Although most cases are self-limited, patients experiencing Shigella infection with severe illness or individuals with high risk of spreading disease should receive antibiotics, wrote Naeemah Logan, MD, an epidemiologist at the CDC’s Division of Foodborne, Waterborne, and Environmental Diseases, and colleagues.

Over the past decade, more cases of shigellosis, a nationally notifiable diarrheal infection caused by gram-negative bacteria, have been caused by strains resistant to many antibiotics, including ampicillin, azithromycin, ceftriaxone, ciprofloxacin, and trimethoprim-sulfamethoxazole, the researchers wrote in a study published in the CDC’s Morbidity and Mortality Weekly Report.

Shigellosis remains an emerging public health concern because of its high transmissibility, and it is increasingly difficult to treat, Logan told Medscape Medical News. A Health Alert from the CDC in 2023 first outlined the rise in XDR Shigella, and the current study provides the first national analysis to better define which populations and regions were most affected, Logan said.

In the study, the researchers reviewed trends in the transmission of XDR Shigella using data from the PulseNet surveillance network from January 1, 2011, to October 20, 2023. The total of 16,788 isolates with resistance data identified during this period included 510 (3%) that were XDR, and the percentage of XDR isolates increased from 0% in 2011 to 8.5% in 2023.

The researchers identified species in 99% of the XDR isolates; 65.9% were Shigella sonnei and 34.1% were Shigella flexneri. The median age of patients with XDR shigellosis was 41 years, and 86.2% were male. More than 75% of patients with available travel histories reported no recent domestic or international travel. In addition, 46.6% of the 116 patients with known HIV status had HIV co-infection, and 37.6% of those with hospitalization data were hospitalized. No deaths were reported in the study population during the study period.

During the period from 2016 to 2023, most of the available data on XDR shigellosis cases came from non-Hispanic White men, and although the current study did not analyze sexual exposure data, previous research has identified sexual contact in men who have sex with men as a significant transmission vector for Shigella, the researchers noted.

Most of the XDR Shigella cases involve S sonnei, the historically dominant strain in the US, but S flexneri was approximately twice as common as the overall US Shigella data (34.1% vs 18.5%). S flexneri has been associated with worse outcomes and an increased risk for death and shows signs of spreading more easily than S sonnei, which makes its presence more concerning in vulnerable populations, Logan told Medscape Medical News.

The findings were limited by several factors, including the likely underestimation of Shigella incidence; lack of antimicrobial susceptibility testing (AST) data for all isolates; limited availability of whole genome sequencing in the early years of the study; and incomplete data on patient demographics, behavioral factors, and travel history, the researchers noted.

However, the results support the need for prevention, early detection, AST-guided therapy, and timely reporting, especially given the potentially greater transmissibility of S flexneri, to protect those at increased risk for resistant infections, they concluded.

Evolving Infections

“What stood out was how much the epidemiology has changed,” Logan told Medscape Medical News. Most strains of Shigella were historically quite drug susceptible and mainly affected children; the disease was often transmitted in daycare settings, she said.

By contrast, the XDR Shigella strains seem to be affecting adults, mainly men, and the lack of travel history in most reported XDR Shigella cases suggests local transmission, Logan added.

Notably, among those with available data, nearly half of the individuals in the current study reported HIV co-infection, and this increase among individuals already at greater risk for infection is sobering, given the limited treatment options, said Logan. An important implication for clinical practice, therefore, is that cases of Shigella may not present as clinicians were originally taught; their index of suspicion for Shigella in adults may be low, she said.

Symptoms of infections from resistant strains are similar to those from drug-susceptible strains, which primarily involve diarrhea and abdominal cramping, but taking a clinical history remains important, Logan told Medscape Medical News. Shigella can affect anyone of any age, and taking a thorough clinical history remains important, she added.

Additional research is needed to better understand transmission dynamics, including the role of sexual networks; monitor the continued emergence of resistance; develop more treatment options for XDR Shigella; and better understand species-specific patterns, including the rising proportion of S flexneri among XDR isolates observed in this analysis, Logan said.

Rapid Rise and Pediatric Protection

The increasing prevalence of XDR shigellosis is concerning because of the lack of oral antibiotic treatment options, said Shirin Mazumder, MD, an infectious diseases specialist and an associate professor at The University of Tennessee Health Science Center in Memphis, Tennessee, who was not involved in the study.

“The rapid rise of XDR Shigella from 0% during 2011-2015 to 8.5% in 2023 is concerning, given that these infections are so difficult to treat,” Mazumder told Medscape Medical News. “In the past, shigellosis was more commonly reported in children; however, men with a median age of 41 were most affected in this study,” she noted.

“Since oral antimicrobial treatment options are limited for XDR shigellosis, increasing patient and clinician education regarding the rising prevalence and promoting prevention methods are necessary,” Mazumder said. Given that more than 45% of those with available HIV status were HIV positive, clinicians should have a high level of suspicion with immunocompromised or other high-risk patients, she said.

Although the population in the current report was mostly adults, XDR Shigella infection in the pediatric population is increasing globally, and similar local trends may emerge in the future, Mazumder told Medscape Medical News. “Since shigellosis is easily spread from person to person via the fecal-oral route, childcare settings allow for increased transmission of infection,” she noted. “Given the emergence of XDR Shigella strains, additional research regarding vaccine development and alternative treatment options are necessary,” she added.

The study received no outside funding. The researchers disclosed having no financial conflicts of interest. Mazumder disclosed having no relevant financial conflicts of interest.