Azithromycin for Bacterial STIs: Which Infections, Which Doses, and When It Is Not Enough

Which Bacterial STIs Does Azithromycin Treat?

Azithromycin is a macrolide antibiotic with activity against a specific range of bacteria, including the intracellular organisms most commonly responsible for bacterial STIs in the UK. Its long tissue half-life—which maintains therapeutic drug concentrations at mucosal sites for 7–10 days after a single oral dose—makes it particularly convenient for STI treatment where single-dose or short-course regimens improve adherence.

However, azithromycin is not a universal STI antibiotic. Its spectrum of activity does not include Neisseria gonorrhoeae at standard doses, and rising resistance rates have altered its first-line status for several indications over the past decade. The following sections set out its current evidence-based role for each bacterial STI it is used to treat in the UK.

Chlamydia — Second-Line Treatment

Chlamydia trachomatis is the most common bacterial STI in the UK, with over 230,000 diagnoses in England each year. Azithromycin was the default first-line treatment for urogenital chlamydia for many years on the strength of its single-dose convenience and reliable cure rates. However, BASHH updated its guidelines in 2025 following evidence that doxycycline achieves superior outcomes, particularly for rectal chlamydia.

For a detailed guide to azithromycin specifically for chlamydia—including full dosing instructions, the comparison with doxycycline, and post-treatment steps—see our dedicated article: Azithromycin for Chlamydia →

Mycoplasma Genitalium — First-Line in Treatment-Naïve Patients

Mycoplasma genitalium (MG) is an increasingly recognised bacterial STI that causes urethritis in men and cervicitis, endometritis, and PID in women. It is estimated to be present in 1–2% of the sexually active UK population and is a growing cause of treatment-resistant STI due to its capacity to develop macrolide resistance.

BASHH 2015/2018 guidelines (reviewed 2022) recommend azithromycin as first-line treatment for M. genitalium in treatment-naïve patients, but the dosing differs significantly from the single 1g dose used for chlamydia. An extended azithromycin regimen is required:

Critically, macrolide resistance in M. genitalium is now detected in approximately 40–50% of UK isolates. For this reason, resistance-guided therapy is now the preferred approach where testing is available: a resistance mutation assay is performed on the positive sample, and if macrolide resistance is detected, moxifloxacin 400mg once daily for 10 days is used instead of azithromycin.

Pelvic Inflammatory Disease — Part of a Combination Regimen

Pelvic inflammatory disease (PID) is an ascending infection of the female upper genital tract, most commonly caused by C. trachomatis, N. gonorrhoeae, M. genitalium, and/or anaerobic organisms. Because PID is polymicrobial, no single antibiotic covers all causative agents, and combination regimens are always required.

Azithromycin plays a limited but recognised role in some outpatient PID regimens. The BASHH 2019 PID guideline outlines several acceptable combination regimens, some of which include azithromycin to provide M. genitalium coverage alongside agents targeting gonorrhoea and anaerobes.

Non-Specific Urethritis and Cervicitis

Non-specific urethritis (NSU) in men and non-specific cervicitis in women describe urethral or cervical inflammation in which a specific causative organism is not identified at the time of initial testing. In practice, C. trachomatis and M. genitalium together account for approximately 40–50% of NSU cases; the remainder involve other organisms including Ureaplasma urealyticum, herpes simplex virus, or no identifiable cause.

BASHH guidelines recommend empirical azithromycin for NSU, given its activity against the two most common bacterial causes:

• First-line empirical treatment for NSU: Doxycycline 100mg twice daily for 7 days (preferred) or azithromycin 1g single dose as an alternative
• Azithromycin 1g may be chosen where single-dose adherence is a practical consideration
• If symptoms persist after initial treatment, further testing for M. genitalium with resistance profiling is recommended before retreating
• Persistent NSU despite two courses of treatment should be managed at a GUM clinic with specialist input

When Azithromycin Is Not Appropriate for STIs

Understanding the limits of azithromycin is as important as knowing its uses. There are several common clinical scenarios in which azithromycin should not be used, or where its use is likely to result in treatment failure:

Dosing by STI Indication

The dose of azithromycin varies depending on the infection being treated. Using the wrong dose risks treatment failure and may contribute to resistance. The table below summarises the BASHH-recommended azithromycin regimens by indication:

Side Effects and Safety

Azithromycin is generally well tolerated. The most common adverse effects are gastrointestinal (nausea, diarrhoea, abdominal discomfort) and are typically mild and self-limiting. Rare but serious effects include QT prolongation and hepatotoxicity. Azithromycin has clinically significant interactions with anticoagulants, antacids, and other QT-prolonging drugs.