The rise of drug-resistant Shigella offers glimpse into danger AMR poses

A significant increase in the percentage of Shigella infections caused by extensively drug-resistant (XDR) versions of the bacteria has prompted the U.S. Centers for Disease Control and Prevention (CDC) to issue a health advisory warning the public of the acute and highly contagious intestinal bug.

As the CDC advisory released Friday pointed out, Shigella infections “resistant to all commonly recommended empiric and alternative antibiotics” have increased from zero in 2015 to 5% in 2022.

Having in mind just how serious the public health threat of XDR shigellosis is, CDC also scheduled a webinar on Tuesday on the “Epidemiology, Testing, and Management of Extensively Drug-Resistant Shigellosis.”

Beyond the immediate health concerns, the drug-resistant strains “can spread antimicrobial resistance genes to other enteric bacteria,” says the CDC.

More than one million people worldwide died in 2019 as a direct result of antimicrobial resistance (AMR) — more than AIDS and malaria. If we don’t develop new antibiotics and antimicrobials, this number could reach 10 million by 2050.

Stomach-turning stats

Per CDC data, “Shigella bacteria cause an infection called shigellosis” that can cause “diarrhea (sometimes bloody), fever, and stomach cramps” which usually “begin 1-2 days after infection and last 7 days.”

The bacteria, according to the CDC, “is transmitted by the fecal-oral route, directly through person-to-person contact including sexual contact, and indirectly through contaminated food, water, and other routes” and typically affects young children but is also on the rise among adults.

Figure: Percentage of Shigella isolates that showed an extensively drug resistant (XDR)* phenotype or genotype in the United States, by year, 2015–2022†
Percentage of Shigella isolates that showed an extensively drug resistant (XDR) phenotype or genotype in the United States, by year, 2015–2022. Graph from emergency.cdc.gov.

Although rarely, Shigella can result in potential complications, which if untreated, can seriously damage health — and even be deadly — such as bloodstream infections, reactive arthritis, and hemolytic-uremic syndrome.

While most patients typically recover without needing antibiotics, “for those who are infected with the drug-resistant strains there are no recommendations for treatment if symptoms become more severe,” explains CNN.

The CDC defines XDR Shigella bacteria “as strains that are resistant to all commonly recommended empiric and alternative antibiotics — azithromycin, ciprofloxacin, ceftriaxone, trimethoprim-sulfamethoxazole (TMP-SMX), and ampicillin.”

That’s quite a lot of antibiotics and commonly used ones. In fact, as CDC points out, “XDR shigellosis is resistant to all generally recommended antibiotics in the U.S.”

Lack of optimal treatment calls for robust pipeline

Currently, “CDC does not have recommendations for optimal antimicrobial treatment of XDR Shigella infections” since there are no data from clinical studies “to inform recommendations for the optimal antimicrobial treatment of these infections.”

Situations like this, as the Biotechnology Innovation Organization’s (BIO) AMR expert Emily Wheeler pointed out, underscore the need for “a robust pipeline of new antimicrobial medicines” to keep pace with ever-increasing rates of resistance.

“This means continually developing new and innovative antimicrobial treatments that are aimed to treat pathogens as they grow resistant,” she noted.

This pipeline, however, “is crumbling due to unique challenges of the antimicrobial marketplace” which., as we previously reported, could be addressed in the U.S. with the help of legislation like the PASTEUR Act (a BIO priority) and the DISARM Act.

 

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