Azithromycin is an antibiotic in the macrolide family, used to treat selected infections caused by susceptible bacteria. It acts on bacterial ribosomes to inhibit protein synthesis. Its clinical uses include certain respiratory, skin, and sexually transmitted infections; effectiveness depends on the organism, its susceptibility, and the site of infection. Initial approval in the United States occurred in 1991. (dailymed.nlm.nih.gov)
Chemical class and mechanism
Azithromycin is a semisynthetic derivative of erythromycin. It belongs to the azalide subgroup of macrolides and has a 15-membered ring containing a nitrogen atom. Its molecular formula is ; pharmaceutical preparations may contain a hydrated form of the compound. (dailymed.nlm.nih.gov)
The drug binds to 23S ribosomal RNA in the 50S subunit of the bacterial ribosome. This inhibits bacterial protein synthesis and interferes with assembly of the ribosomal subunit. The mechanism differs from that of penicillin, which acts on bacterial cell-wall synthesis. (dailymed.nlm.nih.gov)
Distribution and persistence
Azithromycin distributes extensively into tissues and is released slowly from them. Its terminal plasma half-life is approximately 68 hours. This prolonged persistence supports once-daily administration and relatively short treatment courses for some indications, although the regimen varies by infection. Biliary excretion, predominantly as unchanged drug, is a major route of elimination. (dailymed.nlm.nih.gov)
Tissue accumulation is an important pharmacological characteristic, but it does not establish that every organism present in a tissue will be susceptible. Clinical activity also depends on the pathogen and the relationship between drug exposure and bacterial susceptibility. (dailymed.nlm.nih.gov)
Clinical uses
United States oral-product labeling includes selected cases of community-acquired pneumonia, acute bacterial sinusitis, bacterial exacerbations of chronic bronchitis, uncomplicated skin infections, and pediatric otitis media. Pharyngitis and tonsillitis are also listed, with azithromycin designated as second-line therapy. These indications concern specified susceptible organisms rather than every illness sharing the same symptoms. (dailymed.nlm.nih.gov)
Azithromycin also has a role in chlamydial infection. The Centers for Disease Control and Prevention’s 2021 sexually transmitted infection guidelines list it as an alternative for adolescents and adults and as a recommended treatment during pregnancy. Those guidelines distinguish infection sites: evidence shows lower efficacy than doxycycline for rectal chlamydial infection. (cdc.gov)
Separate labeling includes prevention of disseminated Mycobacterium avium complex disease in people with advanced HIV infection, and treatment of disseminated disease in combination with ethambutol. (dailymed.nlm.nih.gov)
Adverse effects and interactions
Common adverse effects include diarrhea, nausea, abdominal pain, and vomiting. Serious reactions described in product labeling include severe hypersensitivity, liver injury, and Clostridioides difficile–associated diarrhea. A history of azithromycin-associated cholestatic jaundice or hepatic dysfunction is a labeled contraindication. (dailymed.nlm.nih.gov)
Azithromycin can prolong the QT interval and is associated with the potentially fatal arrhythmia torsades de pointes. On March 12, 2013, the United States Food and Drug Administration issued a safety communication highlighting this risk. Relevant risk factors include an already prolonged QT interval, low potassium or magnesium concentrations, a slow heart rate, and certain interacting medicines that affect cardiac rhythm. (fda.gov)
Product labeling also describes increased coagulation times with concurrent warfarin use and reports worsening of symptoms in people with myasthenia gravis. (dailymed.nlm.nih.gov)
Resistance and limits of effectiveness
Antibiotic resistance limits azithromycin’s usefulness. A frequently encountered mechanism is modification of its ribosomal RNA target, often by methylation. Such changes can produce cross-resistance to other macrolides and to some related antibiotic classes. Resistance-associated changes in the target RNA also occur in Mycobacterium avium complex. (dailymed.nlm.nih.gov)
Azithromycin was investigated as a treatment for COVID-19, partly because of proposed effects on inflammation. In the RECOVERY randomized controlled trial, adding azithromycin to usual care for hospitalized patients did not improve survival or other prespecified clinical outcomes. That finding concerns treatment of COVID-19 itself and does not negate its antibacterial activity against a separate susceptible bacterial infection. (pmc.ncbi.nlm.nih.gov)
References
- DailyMed — AZITHROMYCIN tablet, film coateddailymed.nlm.nih.gov
- Azithromycin Tablets USP: Initial U.S. Approval, 1991dailymed.nlm.nih.gov
- DailyMed — Azithromycin Tablets, Full Prescribing Informationdailymed.nlm.nih.gov
- DailyMed — AZITHROMYCIN tablet, film coateddailymed.nlm.nih.gov
- Chlamydial Infections — STI Treatment Guidelinescdc.gov
- FDA Drug Safety Communication: Azithromycin (Zithromax or Zmax) and the Risk of Potentially Fatal Heart Rhythmsfda.gov
- Azithromycin in Patients Admitted to Hospital with COVID-19 (RECOVERY): A Randomised, Controlled, Open-Label, Platform Trialpmc.ncbi.nlm.nih.gov