What antibiotics are most likely to cause diarrhea? A guide for patients

October 14, 2025 •

4 min read

Between 5% and 25% of adults taking antibiotics may experience diarrhea as a side effect. Understanding what antibiotics are most likely to cause diarrhea is crucial for managing this common issue, which can range from mild intestinal upset to a severe infection caused by Clostridioides difficile (C. diff).

Quick Summary

Antibiotic-associated diarrhea is a common side effect resulting from gut flora disruption. High-risk medications include cephalosporins, clindamycin, and fluoroquinolones. Management focuses on hydration and, in severe cases, treating a potential C. diff infection.

Key Points

Gut Flora Disruption: Antibiotics kill beneficial bacteria in the intestines, causing an imbalance that can lead to diarrhea.
High-Risk Antibiotics: Certain classes, including cephalosporins, clindamycin, and fluoroquinolones, are more likely to cause diarrhea due to their broad-spectrum action.
C. difficile Infection: In some cases, gut flora disruption allows toxin-producing C. diff bacteria to overgrow, causing severe and potentially dangerous diarrhea.
Probiotics for Prevention: Research suggests that taking probiotics, such as Saccharomyces boulardii, can help reduce the risk of antibiotic-associated diarrhea.
When to Seek Medical Care: Severe or bloody diarrhea, fever, and abdominal cramps during or after antibiotic treatment warrant immediate medical attention, as they may indicate a C. diff infection.
Avoid Anti-Diarrheal Meds: Over-the-counter anti-diarrheal medications should not be taken without a doctor's consent, especially with severe symptoms, as they can worsen a C. diff infection.

The Connection Between Antibiotics and Diarrhea

Antibiotics are powerful medications designed to kill or inhibit harmful bacteria that cause infection. However, they are often not selective and can also disrupt the delicate balance of beneficial bacteria, collectively known as the gut microbiota, that live in your intestines. These 'good' bacteria aid in digestion and help keep opportunistic pathogens in check.

When antibiotics wipe out these helpful microbes, two types of diarrhea can occur:

Simple antibiotic-associated diarrhea: This is the most common type and is typically mild. It is caused by the general disruption of the gut flora and usually resolves on its own within a few days of stopping the medication.
Clostridioides difficile (C. diff) infection: A more serious condition can arise when the loss of beneficial bacteria allows C. diff, a toxin-producing bacterium, to proliferate. The toxins damage the intestinal lining, leading to severe, watery, and sometimes bloody diarrhea, fever, and abdominal cramps.

High-Risk Antibiotics for Causing Diarrhea

While almost any antibiotic can cause diarrhea, certain classes are more frequently associated with this side effect due to their broad spectrum and impact on the gut microbiome. The highest-risk antibiotics are often those that target a wide variety of bacteria, including anaerobes found in the gut.

Notable high-risk classes:

Cephalosporins: This broad-spectrum class includes commonly prescribed antibiotics such as cefdinir (Omnicef), cephalexin (Keflex), and ceftriaxone. Studies have consistently linked third-generation cephalosporins to an increased risk of C. diff infection.
Clindamycin: Clindamycin (Cleocin) is a powerful antibiotic that has a well-known association with causing C. diff infections. Its broad activity can significantly disturb the gut flora, allowing C. diff to flourish.
Fluoroquinolones: This class includes ciprofloxacin (Cipro) and levofloxacin (Levaquin). Fluoroquinolones are associated with a significant risk of both general antibiotic-associated diarrhea and C. diff infection.
Penicillins: Specifically, broad-spectrum penicillins and combination products like amoxicillin-clavulanate (Augmentin) and ampicillin are known to increase the risk of diarrhea. Amoxicillin alone also commonly causes diarrhea.
Macrolides: Macrolide antibiotics, such as clarithromycin (Biaxin), can also disrupt the gut and lead to diarrhea, although the risk may be lower than with some other classes.

A Comparative Look at Diarrhea Risk

Not all antibiotic classes carry the same risk. The risk level depends on factors like the spectrum of bacteria they target, dosage, and duration of use.


Antibiotic Class	Examples	Typical Risk Level	Notes
Cephalosporins	Cefdinir, Cephalexin	High	Broad-spectrum, frequently linked to C. diff.
Clindamycin	Cleocin	Highest	Well-established link to severe C. diff infections.
Fluoroquinolones	Ciprofloxacin, Levofloxacin	High	Significant risk, especially for C. diff and general GI upset.
Penicillins	Amoxicillin-clavulanate, Ampicillin	Moderate to High	Broad-spectrum versions carry higher risk; Amoxicillin alone is also common.
Macrolides	Clarithromycin	Moderate	Associated with diarrhea, but risk may be less than high-risk classes.
Tetracyclines	Doxycycline	Lower	Often cited as having a lower risk of C. diff compared to others.

Managing and Preventing Antibiotic-Associated Diarrhea

If you experience mild diarrhea while on antibiotics, several self-care steps can help manage symptoms. Staying hydrated is essential, and drinking plenty of fluids with electrolytes is recommended. Avoiding dairy, spicy, and high-fiber foods can also help ease discomfort. Over-the-counter anti-diarrheal medications should not be used without a doctor's approval, as they can sometimes worsen infections like C. diff by trapping toxins in the body.

The use of probiotics has shown promise in preventing antibiotic-associated diarrhea. A 2012 meta-analysis published in the Journal of the American Medical Association found that people who took probiotics along with antibiotics were 42% less likely to develop diarrhea. Strains like Saccharomyces boulardii and Lactobacillus rhamnosus GG have been particularly effective. However, individuals with weakened immune systems should consult a healthcare professional before taking probiotics.

For more information on antibiotic-associated diarrhea, consult reliable medical sources such as the Mayo Clinic's overview on the condition.

When to Contact a Doctor

While mild diarrhea is common, certain symptoms may indicate a more serious C. diff infection that requires immediate medical attention. Contact your doctor promptly if you experience any of the following:

More than five loose stools per day
High-volume, watery diarrhea
Severe abdominal pain or cramping
Fever
Blood or pus in the stool
Diarrhea that persists for more than two days after stopping the antibiotic

Conclusion

Antibiotic-associated diarrhea is a common side effect of many antibacterial drugs, stemming from the disruption of the body's natural gut flora. High-risk medications include broad-spectrum agents like cephalosporins, clindamycin, and fluoroquinolones. Managing mild cases involves hydration and a bland diet, while probiotics may offer a preventative measure. However, severe symptoms could signal a dangerous C. diff infection, and prompt medical care is essential. Always finish your prescribed course of antibiotics, but be vigilant for side effects and communicate any concerns with your healthcare provider.

Frequently Asked Questions

Clindamycin is frequently cited as one of the highest-risk antibiotics for causing severe diarrhea, including C. difficile infections. Fluoroquinolones (ciprofloxacin, levofloxacin) and broad-spectrum cephalosporins also carry a significant risk.

Using probiotics, particularly strains like Lactobacillus rhamnosus GG or Saccharomyces boulardii, may help prevent or reduce the severity of antibiotic-associated diarrhea by restoring the balance of good bacteria in the gut. Always consult your doctor before starting a supplement.

Diarrhea can begin shortly after starting an antibiotic course or up to two months or more after completing treatment. This is because the gut flora can remain unbalanced for an extended period.

No, you should not take over-the-counter anti-diarrheal medications without first consulting a doctor. In cases of C. difficile, these medications can worsen the condition by preventing the body from expelling the toxins.

Mild antibiotic diarrhea typically involves occasional loose stools and resolves quickly after stopping the antibiotic. C. diff diarrhea is more severe, often watery and frequent, and can be accompanied by fever, severe abdominal pain, and bloody stool.

Risk factors for developing antibiotic-associated diarrhea include taking broad-spectrum antibiotics, having a longer duration of treatment, advanced age, prolonged hospital stays, and having underlying medical conditions.

It's best to stick to a bland, low-fiber diet, often referred to as the BRAT diet (bananas, rice, applesauce, toast), and consume fluids with electrolytes. Temporarily avoid dairy, spicy, and fatty foods, as they can aggravate the digestive system.