The Prospective Emergence of XDR Shigella Beyond High-Risk Groups

In recent years, extensively drug-resistant (XDR) Shigella cases has climbed in Los Angeles County, where the Department of Public Health (LAC DPH) identified 68 cases in 2024, up from 45 in 2023 and 5 in 2021.¹ The county issued a health advisory in June 2025 warning providers about the increase and the limited antimicrobial options available to treat these infections.¹

“It is such a highly contagious pathogen, [and it] evolved from very susceptible, easy to treat, to highly resistant, very challenging to treat in only a couple decades,” Shangxin Yang, PhD, director of the Molecular Microbiology and Pathogen Genomics Laboratory at UCLA Health, told Contagion in a recent interview. “More importantly, it’s spreading very quietly.”

According to LAC DPH, XDR Shigella disproportionately affects men who have sex with men (MSM) and people living with HIV, who accounted for approximately one-third of county XDR cases reported between 2019 and 2024.¹ Yang estimated roughly 10% of Shigella isolates in the Los Angeles area are now XDR, in line with recent CDC data placing the national figure near 8%.

One of Yang’s biggest concerns around this pathogen is the potential spread beyond high-risk groups. “Not only do we have increasing cases and it’s spreading among [the] MSM population, but it had already spread to the wider population,” said Yang. “What we dread is the foodborne [route], because once it becomes more foodborne, it means more people will be infected.”

XDR Shigella Spreads Beyond MSM in Genomic Surveillance

Yang’s laboratory attempts culture on every PCR-positive stool specimen, performs antimicrobial susceptibility testing (AST) on recovered isolates, and runs whole-genome sequencing (WGS) on resistant strains. He estimated about 90% of US laboratories no longer culture Shigella after a positive molecular result, leaving clinicians blind to resistance. Even with dedicated effort, his team cannot recover roughly 40% of isolates because of the organism’s fastidious nature.

This continuous genomic surveillance recently identified a novel XDR Shigella sonnei genotype carrying the AmpC-type gene blaDHA-1 in 2 unrelated patients with no clear epidemiologic link.³ One was a patient with leukemia and no MSM history, and the other was an unhoused patient living with HIV without a clear sexual exposure. The isolate from the immunocompromised patient carried both blaDHA-1 and the extended-spectrum beta-lactamase (ESBL) gene blaCTX-M-15, a dual cephalosporinase combination not previously reported in Shigella.³

Earlier UCLA Reports on XDR Shigella flexneri and Shigella sonnei

The newest findings build on several years of case-level genomic work at UCLA. In 2022, Yang and colleagues reported a case of persistent, refractory shigellosis caused by XDR Shigella flexneri serotype 2a in an immunocompetent MSM, which Yang described as the first domestically acquired XDR Shigella case in the US.⁴ The isolate carried blaCTX-M-15 rather than the blaCTX-M-27 gene typical of the concurrent UK outbreak, and WGS guided a switch from minocycline to oral fosfomycin 3 g every other day for 3 doses, which cleared the infection.⁴

Phylogenetic comparison linked the 2022 isolate to a multidrug-resistant S flexneri 2a strain the team had sequenced in 2020, suggesting the lineage acquired a plasmid carrying blaCTX-M-15 over roughly 2 years.⁴ Between 2023 and 2024, the group then identified a cluster of 3 XDR S sonnei cases among MSM presenting within 3 months of one another.² All isolates were resistant to azithromycin, ciprofloxacin, ceftriaxone, trimethoprim-sulfamethoxazole, and ampicillin, were highly genetically related, and belonged to a lineage distinct from other circulating strains.²

One patient in the cluster, a 62-year-old man living with HIV, developed septic shock requiring intensive care and initial treatment with meropenem.² Yang noted current isolates have lacked fosfomycin resistance genes, supporting off-label use of oral fosfomycin, though clinical data remain limited. He predicted Shigella could acquire a carbapenemase-carrying plasmid within about 5 years, which would leave agents such as ceftazidime-avibactam among the remaining options.

Yang emphasized culturing PCR-positive specimens, performing AST, and sequencing resistant isolates whenever possible, alongside local surveillance data to guide empiric therapy. He also called for continued development of new oral antibiotics active against resistant Shigella.

References

1.Los Angeles County Department of Public Health. LAC DPH health advisory: increase in extensively drug-resistant Shigella cases in LAC. June 5, 2025. Accessed November 11, 2026. https://ehs.ucla.edu/news/lac-dph-health-advisory-increase-extensively-drug-resistant-shigella-cases-lac

2.Caldera JR, et al. Cluster of extensively drug-resistant Shigella sonnei carrying blaCTX-M-15 in Los Angeles, California, 2023-2024. Am J Infect Control. Published online December 2024. PMID: 39667596

3.Gonzalez-Ferrer S, et al. Emergence of a novel genotype of extensively drug-resistant Shigella sonnei carrying blaDHA-1 in diverse patient populations, Los Angeles, 2024-2025. Antimicrob Steward Healthc Epidemiol. Published online January 2026. PMID: 41562027

4. Caldera JR, Yang S, Uslan DZ. Extensively drug-resistant Shigella flexneri 2a, California, USA, 2022. Emerg Infect Dis. 2023;29(7):1472-1474. doi:10.3201/eid2907.230465