Azithromycin is used to treat chlamydia, chancroid, and mycoplasma genitalium. It also plays a limited backup role in gonorrhea treatment when first-line options aren’t possible. Notably, it is no longer recommended for syphilis due to near-universal resistance. The specific dose and treatment plan vary depending on the infection.
Chlamydia
Chlamydia is the most common reason azithromycin is prescribed as an STD treatment. A single 1-gram oral dose can clear a urogenital chlamydia infection, making it one of the simplest antibiotic regimens available. That convenience is a major advantage: you take one dose and you’re done.
However, azithromycin is now listed as an alternative rather than a first-choice treatment in the CDC’s 2021 guidelines. The preferred option is a week-long course of doxycycline, which has proven more reliable. A meta-analysis of clinical trials found that men treated with azithromycin had higher rates of treatment failure compared to those on doxycycline. The gap is even wider for rectal chlamydia infections. One randomized trial in men who have sex with men found a 100% cure rate with doxycycline versus just 74% with azithromycin for rectal infections.
Azithromycin remains the go-to choice during pregnancy, where doxycycline is not safe to use. It’s also commonly used in expedited partner therapy, a practice where your prescriber gives you medication to pass along to a sexual partner so they can be treated without a separate office visit. Partners who had sexual contact within the previous 60 days are the primary candidates for this approach.
Mycoplasma Genitalium
Mycoplasma genitalium is a lesser-known STI that can cause urethritis in men and cervicitis or pelvic inflammatory disease in women. Treatment for this infection uses azithromycin as part of a two-stage approach rather than as a standalone dose. The current CDC-recommended plan starts with a week of doxycycline to reduce the bacterial load, followed by a higher course of azithromycin: a 1-gram initial dose, then 500 milligrams daily for three more days, totaling 2.5 grams.
This two-stage strategy works best when guided by resistance testing. If the bacteria are sensitive to macrolide antibiotics (the class azithromycin belongs to), this regimen is effective. If resistance is detected, a different antibiotic is used instead. Resistance-guided therapy achieves cure rates above 90%.
Chancroid
Chancroid is a relatively rare STI in the United States, caused by a bacterium that produces painful genital ulcers. A single 1-gram dose of azithromycin is one of the recommended treatments. If the antibiotic is working, ulcer pain typically improves within three days, and visible healing is usually evident within a week.
Gonorrhea: A Shrinking Role
Azithromycin was part of the standard gonorrhea treatment for years, paired with an injectable antibiotic as a dual-therapy approach. That combination was designed to slow the development of antibiotic resistance. It worked for a time, but the bacteria adapted anyway. Between 2013 and 2019, the proportion of gonorrhea samples showing reduced susceptibility to azithromycin increased almost tenfold, reaching 5.1%.
The CDC dropped azithromycin from routine gonorrhea treatment in its 2021 guidelines. The current recommendation is a single injectable antibiotic alone. A high-dose azithromycin regimen (2 grams) was once shown to be 99.2% effective against uncomplicated gonorrhea on its own, but it’s no longer recommended as a standalone treatment because of how quickly resistance is spreading.
The one remaining use is as a backup for people with severe cephalosporin allergies who can’t receive the standard injection. In that case, a 2-gram dose of azithromycin is combined with a different injectable antibiotic.
Syphilis: Not Effective
Azithromycin does not work against syphilis, and you should not rely on it for this purpose. The syphilis-causing bacterium has developed overwhelming resistance. A large North American study found that 99.2% of syphilis samples carried resistance mutations. The WHO stopped recommending azithromycin for syphilis back in 2016, and the research since then has only reinforced that decision. As one infectious disease researcher put it plainly, all syphilis in North America should be assumed azithromycin-resistant. Penicillin remains the standard treatment.
How Azithromycin Works
Azithromycin kills bacteria by interfering with their ability to build proteins. Every bacterium needs to assemble proteins to survive and reproduce, and it does this using molecular machinery called ribosomes. Azithromycin wedges itself into a tunnel inside the ribosome where newly built protein chains exit. With the tunnel blocked, the construction process stalls and the bacterium can no longer function or multiply. This mechanism is why azithromycin is effective against a range of bacterial infections beyond STDs, including respiratory and skin infections.
Safety During Pregnancy and Breastfeeding
Azithromycin is considered safe during pregnancy when an infection requires treatment. It’s the preferred chlamydia treatment for pregnant individuals specifically because doxycycline poses risks to fetal development. Your prescriber will weigh whether azithromycin is the best fit based on the type of infection involved.
Small amounts of azithromycin pass into breast milk, but this is generally not enough to cause problems for a healthy nursing baby. Rare side effects to watch for in a breastfed infant include feeding difficulties, diarrhea, vomiting, rash, oral thrush, or unusual sleepiness.