Azithromycin vs Amoxicillin: Which should you be prescribed?
Azithromycin and amoxicillin are two commonly prescribed antibiotics, each effective against a range of bacterial infections. The choice between them depends on the type of infection, a patient's allergy profile, and practical considerations like dosing convenience. Both are well-studied and considered safe when used appropriately.
What are Azithromycin and Amoxicillin?
Azithromycin is a macrolide antibiotic that works by interfering with bacterial protein synthesis, which stops growth and reproduction of bacteria. Amoxicillin belongs to the penicillin class (specifically beta-lactams) and kills bacteria by disrupting cell wall formation. Each medicine has its own unique mechanism, targeting different types of bacteria.
What Conditions Do They Treat?
Both medications treat overlapping and unique infections:
- Azithromycin is used for respiratory tract infections, bacterial sinusitis, some sexually transmitted infections (STIs), and atypical pneumonias.
- Amoxicillin is standard for strep throat, ear infections (otitis media), dental infections, urinary tract infections (UTIs), and is often preferred for simple, uncomplicated cases.
Effectiveness can vary based on the specific bacteria causing the illness. For example, amoxicillin is often better for treating Streptococcus infections, while azithromycin is favored for organisms not susceptible to penicillins, such as Mycoplasma or Chlamydia.
When Do Doctors Prescribe Azithromycin?
Azithromycin is frequently chosen when penicillin allergy is present and for atypical infections, such as those caused by Mycoplasma, Chlamydia, or Legionella. When convenience matters, azithromycin (Z-Pak) allows shorter treatment durations and once-daily dosing. This can improve adherence for those who may not reliably take multiple daily doses.
When Is Amoxicillin Preferred?
Amoxicillin remains the first-line choice for many simple infections. It is highly effective against Streptococcus species, which cause strep throat and many ear infections. Amoxicillin is generally safe and affordable, and commonly used in children and pregnant individuals unless penicillin allergy is present. Doctors often prescribe it for common conditions like uncomplicated UTIs (caused by susceptible bacteria) and dental abscesses due to its proven track record.
Side Effects and Safety
Azithromycin can cause diarrhea, stomach pain, and nausea as side effects. It also has a rare risk of prolonging the QT interval, which may affect heart rhythm, especially if combined with other QT-prolonging medications. Amoxicillin may cause rash, diarrhea, and nausea. Yeast infections have been reported with both antibiotics.
Both medications have relatively low rates of serious side effects. Taking them with food can help reduce stomach upset.
Convenience and Dosing Differences
For azithromycin, a typical course lasts 1–5 days, taken once daily (often as a Z-Pak for five days). The dose and duration depend on age and the infection being treated. Amoxicillin is usually prescribed for around 10 days, and is taken 2–3 times daily.
Because azithromycin is taken less frequently and typically for a shorter amount of time, it may be preferred for patients with adherence issues. Amoxicillin can be challenging for patients with busy lifestyles or who have problems remembering to take their medication.
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Special Considerations
When considering azithromycin or amoxicillin, healthcare providers must account for individual factors that impact safety and effectiveness. These antibiotics can interact with other medications or underlying health conditions, and their use varies based on age, pregnancy status, and the potential for allergic reactions. These considerations help ensure that patients receive the most appropriate, safe treatment for their needs.
- Pregnancy: Amoxicillin is generally considered safe during pregnancy and breastfeeding. Azithromycin may be indicated in certain situations, and has not been proven to cause adverse outcomes in babies when mothers take it during pregnancy. Your healthcare provider will weigh the risks and benefits of antibiotic treatment.
- Children: Both medications can be used safely in children under the supervision of a healthcare provider. According to the manufacturer of azithromycin, safety has not been established in children under 6 months old for acute otitis media, acute bacterial sinusitis and community-acquired pneumonia and in patients under 2 years old for pharyngitis or tonsillitis.
- Drug interactions: Azithromycin should be used with caution alongside drugs that can prolong the QT interval and anticoagulants, and antacids should not be taken within two hours of azithromycin as they may interfere. Amoxicillin may interact with methotrexate, certain gout medications, anticoagulants, and can reduce the effectiveness of oral contraceptives.
What If Neither Is Suitable?
For patients who cannot take azithromycin or amoxicillin, alternatives include:
- Clindamycin: Used for serious or resistant infections.
- Cephalexin: Commonly prescribed for skin and urinary tract infections.
- Doxycycline: Effective against a wide array of bacteria, including atypical pathogens.
- Bactrim or nitrofurantoin: Often used for UTIs.
Your healthcare provider can recommend an appropriate antibiotic based on your type of infection and possible pathogens that may be causing it.
Bottom Line
Both azithromycin and amoxicillin are valuable antibiotics with proven efficacy. Only a healthcare provider can determine the best option based on the infection, medical history, and risk factors. Self-prescribing or using leftover antibiotics is not safe and can contribute to resistance. Always consult a healthcare professional about the right antibiotic for any bacterial infection.
This is not all the information you need to know about amoxicillin or azithromycin for safe and effective use and does not take the place of your doctor’s directions. Review the full patient medication guide and discuss this information and any questions you have with your doctor or other health care provider.
References
- Akhavan BJ, Khanna NR, Vijhani P. Amoxicillin. [Updated 2023 Nov 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Accessed on September 18, 2025 at https://www.ncbi.nlm.nih.gov/books/NBK482250/
- American Society of Health-System Pharmacists, Inc. (2024, January 15). Azithromycin: MedlinePlus Drug Information. MedlinePlus. https://medlineplus.gov/druginfo/meds/a697037.html
- Amoxicillin [package insert]. Updated October 2024. Micro Labs Limited. Accessed on September 18, 2025 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=42f935ca-45ba-4b3e-8b40-9b2d4eb56281
- Antonucci, R., Cuzzolin, L., Locci, C., Dessole, F., & Capobianco, G. (2022). Use of Azithromycin in Pregnancy: More Doubts than Certainties. Clinical drug investigation, 42(11), 921–935. https://doi.org/10.1007/s40261-022-01203-0
- Azithromycin tablet [package insert]. Updated November 2023. Precision Dose, Inc. Accessed on September 18, 2025 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d9b66736-3f1a-4d6d-bdc4-274f5adfb40c
- National Health Service. (2022, January 20). Pregnancy, breastfeeding and fertility while taking azithromycin. NHS. Retrieved September 18, 2025, from https://www.nhs.uk/medicines/azithromycin/pregnancy-breastfeeding-and-fertility-while-taking-azithromycin/
- Ovetchkine, P., Rieder, M. J., & Canadian Paediatric Society, Drug Therapy and Hazardous Substances Committee (2013). Azithromycin use in paediatrics: A practical overview. Paediatrics & child health, 18(6), 311–316. PMCID: PMC3680256 PMID: 24421702
- Patel, H., Calip, G. S., DiDomenico, R. J., Schumock, G. T., Suda, K. J., & Lee, T. A. (2020). Comparison of Cardiac Events Associated With Azithromycin vs Amoxicillin. JAMA network open, 3(9), e2016864. https://doi.org/10.1001/jamanetworkopen.2020.16864
- Ronchera, C. L., Hernández, T., Peris, J. E., Torres, F., Granero, L., Jiménez, N. V., & Plá, J. M. (1993). Pharmacokinetic interaction between high-dose methotrexate and amoxycillin. Therapeutic drug monitoring, 15(5), 375–379. https://doi.org/10.1097/00007691-199310000-00004
- Sandman Z, Iqbal OA. Azithromycin. [Updated 2024 Nov 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Accessed on September 18, 2025 at https://www.ncbi.nlm.nih.gov/books/NBK557766/
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