Nearly all syphilis strains in U.S. resistant to azithromycin

Nearly all isolates of the bacterium that causes syphilis bear mutations that make them resistant to the antibiotic azithromycin, according to a study of samples collected from the United States and Canada. 

The findings were reported June 12 in the New England Journal of Medicine. Nicole Lieberman, a senior scientist in laboratory medicine and pathology at the University of Washington School of Medicine, is first author. Dr. Alex Greninger, associate professor in the department, led the study.

U.S. syphilis cases have surged. Cases nearly doubled from 114,000 in 2018 to more than 203,000 in 2022. Of particular concern is the growing number of infants born with congenital syphilis, which can have devastating consequences including vision loss, physical deformities and neurological damage. 

The infection is cause by the bacterium Treponema pallidum. Most cases can be treated effectively with a single injection of a long-acting form of penicillin called benzathine penicillin G. But increased worldwide demand for the antibiotic has caused many providers to run out. 

As a result, some physicians have contemplated using azithromycin, an antibiotic recommended as an alternative until about 15 years ago, when resistance was found in more than half of syphilis samples. 

Although other drugs are available to treat syphilis, treatment with some of these alternatives, such as doxycycline, requires taking pills twice daily for up to 28 days. Many patients fail to complete such long courses of drug of treatment, thereby increasing their risk that the infection will not be eradicated.

“We did this study because we started getting calls from healthcare providers in the community interested in using azithromycin, which is a single oral dose,” Lieberman said. “These community stakeholders in public health, primary care, and other areas are now suddenly seeing more cases of syphilis. They’d say, ‘I know azithromycin is not recommended, but my patient may not be able to complete two weeks of doxycycline.’ ”

Because most of the reports examining azithromycin resistance in the United States were more than a decade old, Lieberman and her colleagues decided to investigate resistance levels today. They looked for mutations known to confer azithromycin resistance in more than 600 isolates collected in the United States and Canada over the past six years.

They found that 99.2% of the bacteria harbored mutations that allow them to resist macrolide antibiotics such as azithromycin.

“Our data do not support the use of azithromycin as a treatment option for syphilis in the United States or Canada, even in the context of limited alternatives owing to shortages of benzathine penicillin G,” the researchers concluded. “If faced with shortages of benzathine penicillin G, clinicians should choose doxycycline or ceftriaxone, not azithromycin, in nonpregnant patients with syphilis.”

For pregnant patients and newborns, penicillin remains the only treatment option, the researchers noted.

Other authors on the report represent UW Medicine’s Department of Laboratory Medicine and Pathology and Division of Allergy and Infectious Diseases, as well as Public Health – Seattle & King County, public health agencies in California and British Columbia, academic institutions and labs in Alabama, Alberta, Georgia, North Carolina and Wisconsin, and the U.S. National Institutes of Health and Centers for Disease Control and Prevention.

This work was supported by the National Institute of Allergy and Infectious Diseases (U19 AI144133, R01 AI155442, HHSN272201300012).

Written by Michael McCarthy

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