In Los Angeles County, the number of cases of extensively drug-resistant (XDR) Shigella has risen significantly, with the Department of Public Health (LAC DPH) reporting 68 cases in 2024, a substantial increase from the 45 cases in 2023 and just 5 cases in 2021.¹ This prompted the county to issue a health advisory in June 2025, alerting healthcare providers to the growing problem and the limited treatment options available for these infections.¹
Shangxin Yang, PhD, director of the Molecular Microbiology and Pathogen Genomics Laboratory at UCLA Health, highlighted the alarming evolution of Shigella in a recent interview with Contagion, stating, “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.” Yang also noted, “More importantly, it’s spreading very quietly.”
According to data from the LAC DPH, XDR Shigella disproportionately affects certain populations, including men who have sex with men (MSM) and individuals living with HIV, who together accounted for approximately one-third of the county’s reported XDR cases between 2019 and 2024.¹ Yang estimated that roughly 10% of Shigella isolates in the Los Angeles area are now XDR, which is consistent with recent CDC data indicating a national figure of around 8%.¹
Yang expressed concern about the potential for XDR Shigella to spread beyond high-risk groups, saying, “Not only do we have increasing cases and it’s spreading among [the] MSM population, but it had already spread to the wider population.” He further emphasized, “What we dread is the foodborne [route], because once it becomes more foodborne, it means more people will be infected.”
Genomic Surveillance Uncovers Emerging Threats
Yang’s laboratory employs a wide-ranging approach to monitoring XDR Shigella, including culturing every PCR-positive stool specimen, conducting antimicrobial susceptibility testing (AST) on recovered isolates, and performing whole-genome sequencing (WGS) on resistant strains. However, Yang estimated that about 90% of US laboratories have discontinued culturing Shigella after a positive molecular result, which can leave clinicians unaware of the level of resistance. Despite dedicated efforts, his team is unable to recover around 40% of isolates due to the organism’s fastidious nature.
Recent genomic surveillance has identified a novel XDR Shigella sonnei genotype carrying the AmpC-type gene blaDHA-1 in two unrelated patients without a clear epidemiologic link.³ One patient had leukemia and no history of MSM, while the other was an unhoused individual 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 previously unreported combination in Shigella.³
Previous research at UCLA has demonstrated the rapid accumulation of resistance in Shigella. 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, and WGS guided a treatment switch from minocycline to oral fosfomycin, which successfully cleared the infection.⁴
A phylogenetic comparison linked the 2022 isolate to a multidrug-resistant S flexneri 2a strain sequenced in 2020, suggesting that the lineage acquired a plasmid carrying blaCTX-M-15 over approximately two years.⁴ Between 2023 and 2024, the group identified a cluster of three XDR S sonnei cases among MSM presenting within three months of each other.² All isolates were resistant to multiple antibiotics, including azithromycin, ciprofloxacin, and ampicillin, and were highly genetically related, belonging to a distinct lineage.²
Researchers at UCLA have tracked the lineage’s acquisition of resistance genes over time.
Treatment Options and Future Risks
One patient in the cluster, a 62-year-old man living with HIV, developed septic shock and was initially treated with meropenem.² Yang noted that current isolates lack fosfomycin resistance genes, supporting the off-label use of oral fosfomycin, although clinical data are limited. He predicted that Shigella could acquire a carbapenemase-carrying plasmid within about five years, which would leave few treatment options, including agents like ceftazidime-avibactam.
Yang emphasized the importance of 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, highlighting the need for effective treatments against this emerging threat.