Can Azithromycin Cause Diarrhea? Understanding the Gut Connection

October 8, 2025 •

4 min read

According to clinical trials, up to 5% of people taking a standard dose of azithromycin have reported experiencing diarrhea, making it one of the most common side effects. This gastrointestinal upset, while often mild and temporary, is a recognized risk associated with taking this and other antibiotics.

Quick Summary

Azithromycin, like most antibiotics, can disrupt the natural balance of bacteria in the gut, leading to diarrhea. Most cases are mild and resolve after treatment ends. However, an overgrowth of harmful bacteria like C. difficile can cause severe, potentially delayed diarrhea. Management includes dietary changes and, for some, probiotics.

Key Points

Common Side Effect: Diarrhea is one of the most frequently reported side effects of azithromycin, caused by its effect on gut bacteria.
Mild vs. Severe: Mild diarrhea is common and typically resolves on its own, but severe, bloody diarrhea could indicate a more serious infection with C. difficile.
Gut Microbiome Disruption: The antibiotic kills beneficial gut bacteria, leading to an imbalance that causes digestive upset.
Delayed Onset Possible: C. difficile infection can manifest not only during azithromycin treatment but also weeks or months after the course is finished.
Diet and Hydration: For mild cases, focus on staying hydrated and eating bland foods like bananas, rice, applesauce, and toast (BRAT diet).
Probiotics May Help: Supplements or yogurt containing live active cultures can help restore gut flora, but consult a doctor first, especially if immunocompromised.
When to See a Doctor: Seek immediate medical attention if you develop severe, bloody, or persistent diarrhea, fever, or severe abdominal pain.

The Link Between Azithromycin and Diarrhea

Azithromycin, often prescribed as a Z-Pak, is a powerful macrolide antibiotic used to treat various bacterial infections, including respiratory and skin conditions. While effective against harmful bacteria, it is not always selective and can disrupt the natural, beneficial bacteria residing in the gastrointestinal (GI) tract. This disruption, known as dysbiosis, is the primary reason why antibiotics can cause diarrhea.

How Antibiotics Disrupt Gut Flora

The human gut is home to trillions of microorganisms, collectively known as the gut microbiome, which aid in digestion and protect against pathogens. When azithromycin is introduced, it kills off susceptible bacteria throughout the body, including beneficial gut bacteria. This creates a void that can be filled by opportunistic, and sometimes harmful, bacteria. This imbalance leads to digestive upset and the characteristic loose, watery stools of antibiotic-associated diarrhea. Studies in children have shown that azithromycin can cause a significant, short-term reduction in the diversity of gut microbiota, particularly affecting the abundance of beneficial bacteria like Bifidobacterium.

The Role of Clostridioides difficile (C. diff)

While most antibiotic-associated diarrhea is mild, a more serious condition can develop, known as Clostridioides difficile-associated diarrhea (C. diff or CDAD). This occurs when the antibiotic treatment allows the C. difficile bacteria, which may already be present in small amounts, to multiply unchecked and release toxins. C. diff infection is a major concern, as it can range from severe diarrhea and abdominal pain to life-threatening colitis. Importantly, CDAD can occur not only during treatment but also weeks or even months after the antibiotic course is completed.

Symptoms: Distinguishing Mild from Severe

Recognizing the difference between typical antibiotic-associated diarrhea and a more serious C. diff infection is crucial for knowing when to seek medical help.

Common and Mild Side Effects

Mild diarrhea is a relatively common side effect of azithromycin. In clinical trials, rates varied depending on the dose, with higher doses increasing the risk. Other common GI side effects often accompany it.

Common GI side effects with azithromycin:

Nausea
Vomiting
Abdominal pain or cramping
Mild, loose stools

These symptoms are typically manageable and subside shortly after the medication is stopped.

Signs of Severe Diarrhea (C. diff)

Severe, infectious diarrhea caused by C. diff requires immediate medical attention.

Symptoms of C. diff infection:

Severe, watery, or bloody diarrhea
High fever
Severe abdominal cramps
Rapid heart rate
Loss of appetite

Comparison Table: Mild Diarrhea vs. C. diff Diarrhea


Feature	Mild Azithromycin Diarrhea	C. difficile-Associated Diarrhea (C. diff)
Onset	Usually occurs during or shortly after antibiotic treatment.	Can occur during treatment or up to two months after stopping.
Severity	Typically mild to moderate.	Can be severe and even life-threatening.
Stool Consistency	Loose or watery stools, usually 2-4 times a day.	Very watery or bloody stools, potentially very frequent (up to 15 times/day).
Accompanying Symptoms	May include mild nausea, vomiting, or stomach pain.	Includes high fever, severe abdominal pain, and potential for rapid heart rate.
Duration	Resolves within a few days of stopping the antibiotic.	Can be persistent and may require specific antibiotics for treatment.
Management	Often managed with dietary changes and hydration.	Requires immediate medical evaluation and specific antibiotic therapy.

Management and Prevention

For mild cases, simple strategies can help manage discomfort. For more severe symptoms, a doctor's guidance is essential.

What to Do for Mild Diarrhea

Stay Hydrated: Drink plenty of clear fluids, like water, broth, or electrolyte drinks, to replace lost fluids and prevent dehydration.
Modify Your Diet: Stick to bland, low-fiber, starchy foods, such as the BRAT diet (bananas, rice, applesauce, toast), until symptoms improve.
Avoid Irritating Foods: Steer clear of spicy, greasy, high-fiber, or dairy-heavy foods, which can aggravate the digestive tract.

The Role of Probiotics

Probiotics are live bacteria and yeasts that can help replenish the 'good' bacteria in your gut. Taking a probiotic supplement or eating probiotic-rich foods like yogurt with live cultures while on antibiotics may help mitigate the risk of diarrhea. Some studies suggest specific strains like Lactobacillus rhamnosus GG and Saccharomyces boulardii are most effective. However, people with weakened immune systems should consult a doctor before starting probiotics.

Preventing Antibiotic-Associated Diarrhea

Prevention starts with prudent antibiotic use. Only take antibiotics when necessary and complete the full prescribed course, even if you feel better. Inform your doctor if you have a history of antibiotic-associated diarrhea so they can prescribe an alternative medication if appropriate.

When to Consult a Doctor

While mild diarrhea is a manageable side effect, some symptoms warrant a call to your healthcare provider.

Consult a doctor if you experience:

Severe, watery, or bloody diarrhea
Fever along with diarrhea
Diarrhea that does not improve after you finish the medication
Diarrhea that starts weeks after your treatment ends
Severe stomach pain or cramps

Conclusion

Yes, azithromycin can and often does cause diarrhea by disrupting the gut's normal bacterial balance. This side effect is typically mild and resolves on its own. However, in some cases, it can escalate into a more severe and serious condition caused by C. difficile. The key to managing this risk is being proactive: practice good gut health habits with dietary support and probiotics, recognize the symptoms that signal a more serious problem, and always consult your doctor if you have concerns. Understanding the reasons behind this common side effect empowers patients to manage their health effectively during and after antibiotic therapy.

For more information on antibiotic-associated diarrhea, consult the official resources from the Centers for Disease Control and Prevention (CDC). CDC: About Clostridioides difficile

Frequently Asked Questions

Yes, diarrhea is a common side effect of azithromycin, though it is usually mild. Clinical trials reported that up to 5% of participants experienced diarrhea with standard doses.

Normal antibiotic diarrhea is typically mild, watery, and resolves once you stop the medication. Severe diarrhea, often caused by C. difficile, is characterized by frequent, watery, or bloody stools, fever, and severe abdominal pain.

For mild diarrhea, focus on staying well-hydrated with water and electrolyte drinks. Eating a bland diet (like the BRAT diet) and avoiding spicy, greasy, or high-fiber foods can also help.

Taking probiotics, such as yogurt with live cultures or supplements with strains like Saccharomyces boulardii, may help restore gut bacteria and prevent diarrhea. However, you should always discuss this with your doctor, especially if you have a compromised immune system.

You should contact your healthcare provider immediately if you experience severe, watery, or bloody diarrhea, a fever, severe abdominal cramping, or if diarrhea persists after finishing your medication.

For most people, mild diarrhea resolves within a few days of stopping the medication. However, severe C. difficile infection can cause delayed or prolonged diarrhea that requires specific treatment.

Yes, the risk and severity of gastrointestinal side effects, including diarrhea, can be dose-related. People taking higher doses of azithromycin have reported a higher incidence of diarrhea in clinical trials.

You should not take anti-diarrheal medications without first speaking with your doctor. In cases of C. difficile infection, these medications can trap toxins in the colon and worsen your condition.