Can Mupirocin Cause Diarrhea? Understanding a Rare but Serious Risk

October 13, 2025 •

3 min read

Though a topical antibiotic with minimal systemic absorption, mupirocin has been associated with a rare but serious systemic side effect: Clostridioides difficile-associated diarrhea (CDAD). This risk, which is present with nearly all antibiotics, occurs when the medication disrupts the normal balance of healthy bacteria in the gut.

Quick Summary

Mupirocin can cause a rare form of severe diarrhea linked to C. difficile overgrowth, potentially occurring weeks after use. The risk is higher with large or damaged skin application and requires immediate medical attention for severe symptoms.

Key Points

Mupirocin can cause diarrhea: Although a topical antibiotic, it can rarely lead to diarrhea, most notably a severe form called Clostridioides difficile-associated diarrhea (CDAD).
Low systemic absorption: The risk is low because less than 1% of the medication is typically absorbed through intact skin.
Higher risk on damaged skin: Absorption increases significantly when applied to large open wounds or damaged skin, elevating the risk of systemic side effects like CDAD.
Delayed onset is possible: CDAD symptoms can appear up to two months after stopping the use of mupirocin.
Know the severe signs: Seek immediate medical help for watery or bloody diarrhea, fever, and severe abdominal cramps, as these can indicate a serious C. diff infection.
Avoid self-medicating for diarrhea: Do not take over-the-counter anti-diarrheal medications without a doctor's advice, especially if you suspect a C. diff infection.
Inform your doctor: Always inform your healthcare provider if you experience any signs of diarrhea or other side effects while using mupirocin.

The Mechanism of Antibiotic-Associated Diarrhea

Mupirocin is an antibiotic applied topically to the skin to treat bacterial infections like impetigo. Its primary action is localized, killing bacteria at the site of infection by inhibiting bacterial protein synthesis. Due to its topical nature, very little of the medication is absorbed into the bloodstream when applied to intact skin, typically less than 1%.

However, even with minimal systemic absorption, like all antibacterial agents, mupirocin carries a risk of disrupting the delicate ecosystem of bacteria in the colon, known as the gut flora. When the balance of 'good' bacteria is disturbed, opportunistic and harmful bacteria, such as Clostridioides difficile (also called C. diff), can proliferate and cause a serious infection. The risk of systemic side effects, though rare, increases if the medication is applied to large areas of damaged skin, such as large open wounds or burns, as this allows for more medication to enter the body.

Mupirocin and Clostridioides difficile-Associated Diarrhea (CDAD)

The most concerning form of diarrhea associated with antibiotic use is CDAD. It is crucial to distinguish this from milder, short-lived diarrhea that might accompany some antibiotic use. C. diff bacteria produce toxins that can cause severe inflammation of the colon, known as colitis.

Symptoms of CDAD can be severe and life-threatening, and may not appear until several weeks after stopping the antibiotic treatment. This delayed onset is a key factor distinguishing it from more common, mild gastrointestinal upset.

Recognizing the Symptoms: Mild vs. Severe Diarrhea

It is important for patients to recognize the signs that differentiate a minor, temporary gut disturbance from a more serious C. difficile infection. The following table provides a comparison of symptoms:


Symptom	Mild Antibiotic-Associated Diarrhea	Clostridioides difficile-Associated Diarrhea (CDAD)
Onset	Often occurs during or shortly after starting antibiotic treatment.	Can occur during treatment or up to two months after stopping the antibiotic.
Stool	Loose, watery stools, but not necessarily frequent or severe.	Severe, watery, or bloody stools; may be highly frequent.
Associated Pain	Mild stomach or abdominal discomfort.	Severe abdominal or stomach cramps and pain.
Other Symptoms	Typically limited to gastrointestinal upset.	Fever, nausea, rapid heart rate, loss of appetite, bloating.

Risk Factors and Precautions

While anyone using an antibiotic can develop CDAD, certain factors increase the risk:

Long-term use: Prolonged antibiotic courses can increase the chances of altering the gut flora significantly.
Use of multiple antibiotics: Taking several antibiotics simultaneously or in close succession heightens the risk.
Advanced age: Individuals aged 65 years and older have a higher risk.
Weakened immune system: People with compromised immune systems are more susceptible.
Recent hospitalization: Hospital stays can increase exposure to the C. difficile bacteria.
History of CDAD: A previous C. diff infection increases the likelihood of recurrence.
Large areas of application: Applying topical mupirocin to large areas of broken skin or open wounds increases systemic absorption and, therefore, systemic risk.

What to Do If You Experience Diarrhea

If you or someone you know develops diarrhea while using mupirocin, follow these steps:

Monitor the severity. Pay close attention to the nature of the diarrhea and any accompanying symptoms like fever or severe pain.
Contact a healthcare professional. If the diarrhea is severe, watery, or bloody, or accompanied by fever or abdominal pain, seek immediate medical attention.
Do not use anti-diarrheal medication. Over-the-counter treatments can interfere with the body's ability to eliminate toxins and worsen a C. difficile infection. Never take them without consulting a doctor first.
Stay hydrated. Drink plenty of fluids to prevent dehydration, especially if the diarrhea is persistent. Electrolyte-rich drinks or oral rehydration solutions are helpful.
Inform your doctor. Tell your doctor about your diarrhea, even if it is mild. They will determine if the mupirocin treatment needs to be stopped or if a different course of action is required.

Conclusion

While mupirocin is a topical medication with minimal systemic absorption, a rare but serious side effect is Clostridioides difficile-associated diarrhea (CDAD). This occurs because, like all antibiotics, it can alter the normal gut flora. The risk is elevated in certain patient populations and with increased systemic exposure, such as applying it to large areas of damaged skin. It is vital to recognize the difference between mild antibiotic-associated diarrhea and severe, potentially delayed-onset CDAD symptoms and to contact a healthcare provider immediately if serious symptoms arise. Never self-treat with antidiarrheal medications without a doctor's approval when suspecting CDAD. For more information, consult resources like the Mayo Clinic.

Frequently Asked Questions

Yes, although it is rare, topical medications can be absorbed into the bloodstream. In the case of mupirocin, this absorption can be enough to disturb the normal gut flora, potentially leading to Clostridioides difficile overgrowth and causing diarrhea.

Mild antibiotic-associated diarrhea is usually less severe and resolves quickly. C. difficile diarrhea is characterized by more severe, watery, or bloody stools, and may be accompanied by fever, severe abdominal cramps, and bloating. It can also occur weeks after stopping the medication.

If you experience mild diarrhea, continue your treatment as prescribed but inform your doctor. They can determine if the symptoms are related to the medication and if any adjustments are needed. Make sure to stay hydrated.

Seek immediate medical attention if you experience severe, watery, or bloody diarrhea, severe abdominal pain or cramping, or fever. These could be signs of a serious Clostridioides difficile infection.

Yes. Only use mupirocin as directed and for the prescribed duration. Avoid applying it to large areas of severely damaged skin. If you have risk factors for C. difficile, your doctor may suggest additional precautions.

You should not use over-the-counter anti-diarrheal medication without consulting a doctor first, especially if you suspect C. difficile. These medications can trap toxins in your system and worsen the condition.

Diarrhea, particularly the severe form caused by C. difficile, is a rare side effect of topical mupirocin. However, like all antibiotics, the risk is present and patients should be aware of the symptoms.