LOS ANGELES -- Three men sought help at clinics or emergency rooms in Los Angeles County over a three-month period this year, each reporting severe diarrhea and a recent history of sexual contact with other men.
Stool cultures revealed that all three were infected with Shigella sonnei, a strain of Shigella bacteria that is resistant to five of the antibiotic classes most commonly prescribed for such infections. But upon further analysis, the UCLA researchers analyzing the samples realized they were looking at something altogether new.
All three cases had a distinct genetic mutation that made the bacteria resistant to yet another class of antibiotics, the cephalosporins, which are often used to treat Shigella infections when other drugs fail.
The strain appears to be unique to Los Angeles and has not been recorded anywhere else, said Dr. Shangxin Yang, a UCLA molecular biologist and clinical microbiologist who is a co-author of the paper describing the find. Although all the patients ultimately recovered, the mutation represents an unsettling new development in a battle against a tiny but hardy foe.
"It's very alarming," Yang said. "We are dealing with a very stealthy pathogen, and it's really successful in spreading in a community."
Two years ago, the U.S. Centers for Disease Control began tracking a sharp rise in cases of extensively drug-resistant (XDR) shigellosis -- infections by particular strains of Shigella bacteria that are impervious to most antibiotics.
The Los Angeles County Department of Public Health reported 45 cases of XDR shigellosis in 2023, up from just five in 2021. The antibiotic-resistant infection causes diarrhea, nausea and stomach cramping and is spreading primarily among men who have sex with other men.
The number of cases detected this year declined somewhat from the 2023 peak, with 30 such infections reported in the county.
But Shigella sonnei, the parent strain of the new ultra-resistant bug discovered at UCLA, remains a tricky pathogen for multiple reasons, Yang said.
For one, many infections are either asymptomatic or relatively mild, allowing people to pass the disease to others without realizing they are sick.
It's a tough bacteria to grow in the lab, which makes it harder for pathologists to identify which particular strain they're dealing with, he added. And without being able to identify which bacteria is sickening the patient and prescribe the appropriate treatment, the duration of the infection -- and period in which it can be spread to other people -- is prolonged.
"What we found is probably only a fraction of what's really in the community," Yang said.
Most shigellosis patients, even those infected with drug-resistant strains, will get better on their own without a need for antibiotics, said Dr. Daniel Uslan, an infectious disease specialist at UCLA and a co-author of the paper.
But for patients with compromised immune systems, these infections can lead to serious complications that can't be easily cured. One of the three patients identified in the recent paper, a 62-year-old man with a history of HIV/AIDS and hepatitis C, was ill enough to be admitted to the intensive care unit with septic shock. He was ultimately treated successfully with meropenem, an antibiotic used sparingly as a last line of defense against infections resistant to other medications.
"This is not a cause for panic. It's a cause for caution and alarm," Uslan said.
More broadly, the appearance of a new drug-resistant bacteria is a troubling development in the fight against "superbugs," or pathogens resistant to most available antibiotics.
A study in the medical journal Lancet this year found that without new medications, "superbug" infections could kill nearly 2 million people a year in 2050 -- a 67.5% increase from the 1.14 million lives lost this way in 2021.
An additional 8.22 million will die of causes related to those infections in 2050, according to a study from the Global Research on Antimicrobial Resistance Project.
In June, the World Health Organization warned that far too few new antibiotics are in the global development pipeline, and the ones that are there fall far short of the innovation required to vanquish the most dangerous microbes.
"The discovery of any extensively antibiotic-resistant bacteria is alarming, especially in cities like Los Angeles," said Henry Skinner, chief executive of the AMR Action Fund, which invests in antimicrobial drugs.
"The bacterium detailed in this report is resistant to some of our most widely used antibiotics, including ciprofloxacin and azithromycin -- medicines that tens of thousands of patients depend on daily," he said. "With so few new antibiotics in development, it's very concerning to learn that an XDR strain of Shigella may be gaining a foothold in the U.S."