Which Antibiotics Are Less Likely to Cause Diarrhea From C. diff?

Infections are very common — about 23 million people in the U.S. look to get infections treated every year. Infections are generally caused by germs, including bacteria, viruses, and parasites. 

If you have a bacterial infection, there’s a good chance you’ll receive an antibiotic. While an appropriately chosen antibiotic will likely treat the bacterial infection, it may also come with side effects. For example, many antibiotics can cause diarrhea.

In some cases, antibiotics may also lead to a more serious form of diarrhea. It’s possible that they could cause a Clostridium difficile (C. difficile or “C. diff”) infection. This type of infection causes severe, infectious diarrhea and colon inflammation. All antibiotics can raise your risk for C. diff infection (CDI) and CDI-related diarrhea. But some are more likely to cause it than others. 

Let’s take a look at some common antibiotics and whether they have a higher or lower risk for CDI than other antibiotics.

Why do antibiotics cause C. diff-related diarrhea?

All antibiotics carry some CDI risk because they may affect your gut bacteria. The changes in your gut bacteria encourage C. diff to become active and secrete toxins. These toxins can cause diarrhea and make people feel very sick. 

Which antibiotics are more likely to cause C. diff-related diarrhea?

When you take an antibiotic, you’re more likely to have certain side effects over others. These are a few of the common antibiotics considered to be high risk for CDI-related diarrhea.

1. Clindamycin (Cleocin)

Clindamycin is in a very small antibiotic class called lincosamides. It treats a variety of infections, including MRSA (methicillin-resistant Staphylococcus aureus) skin infections and vaginal infections. But, it’s a known culprit in CDI.

2. Amoxicillin/clavulanate (Augmentin)

Augmentin is a combination antibiotic that contains amoxicillin and clavulanate. Amoxicillin is a penicillin-like antibiotic. And clavulanate is a beta-lactamase inhibitor. Clavulanate helps prevent amoxicillin from breaking down. It does this by stopping a type of protein called beta-lactamase. 

You may see Augmentin used for:

• Ear infections

• Sinus infections

• Lung infections, like pneumonia

While it’s a go-to for a number of infections, it also has a high CDI risk.

3. Cephalosporins

Cephalosporins are another class of antibiotics that may cause C. diff diarrhea. The class includes medications like cefdinir and cefpodoxime. This family of antibiotics can be used for several infections. For example, cefdinir and cefpodoxime are commonly used for sinus infections and ear infections.

4. Tetracyclines

The tetracycline antibiotic class includes a number of antibiotics, including doxycycline (Oracea) and minocycline (Minocin). Doxycycline is the most commonly used tetracycline antibiotic, and it can treat various infections. Besides acne, doxycycline can also be used to treat:

• Lyme disease

• Lung infections

• Sexually transmitted infections (STIs), like chlamydia

• Skin infections

Minocycline is used less often, and it’s primarily prescribed to treat acne.

5. Clarithromycin

Clarithromycin is in the macrolide antibiotic class. It’s used for a number of infections, including lung infections. You may also see it used in combination with multiple medications to treat Helicobacter pylori (H. pylori) infections, which is bacteria that can cause stomach ulcers. Interesting note: you may notice a weird metallic taste in your mouth as a side effect.

Which antibiotics cause C. diff-related diarrhea less often?

Compared to the medications listed above, some antibiotics are less likely to cause CDI. They may still lead to CDI, but the odds are much lower.

Below are antibiotics with a lower risk of CDI-related diarrhea.

1. Sulfamethoxazole/trimethoprim (Bactrim)

Sulfamethoxazole/trimethoprim is often prescribed for conditions like urinary tract infections (UTIs) and traveler’s diarrhea. Compared to many antibiotics, Bactrim has a low risk for CDI-related diarrhea.

2. Quinolones

Quinolones (fluoroquinolones) are a medication class with several family members. As a class, the quinolones may fight many different kinds of bacteria. A number of these antibiotics are also fairly convenient, as they generally need to be taken only once a day. 

In the past, you may have heard that quinolones are more likely to cause C. diff than other antibiotics. They may still cause C. diff, but based on a 2016 meta analysis, this doesn’t appear to be the case. The risk may be lower than originally thought. 

Quinolones include popular medications like levofloxacin and ciprofloxacin (Cipro). You may see levofloxacin or ciprofloxacin used for serious UTIs, skin infections, lung infections, and more.

3. Azithromycin (Zithromax, Z-Pak)

Like clarithromycin, azithromycin (Zithromax, Z-pak) is a macrolide antibiotic. Azithromycin might be used for many different types of infections, including strep throat, chlamydia, and lung infections, among many others. 

Researchers were also looking at azithromycin combined with minocycline as a possible treatment for COVID-19. But experts don’t recommend using either medication against COVID-19. 

5. Metronidazole (Flagyl)

Metronidazole is an antibiotic option that can actually treat C. diff diarrhea. Think of metronidazole as an antibiotic that’s typically used for infections from the waist down, such as: 

• STIs

• Bacterial vaginosis

• Pelvic inflammatory disease

• C. diff

You may also see it combined with other medications to treat digestive tract-related infections.

Why trust our experts?

Written by:

Ross Phan, PharmD, BCACP, BCGP, BCPS

Ross Phan is a board-certified clinical pharmacist. She has roughly two decades of healthcare experience — with most of her experience being pharmacy related.

Edited by:

Samvida Patel, MNSP, INHC

Samvida Patel, MNSP, INHC, is a health editor at GoodRx. She is a nutritionist and integrative nutrition health coach with over 8 years of experience in health communications.

Reviewed by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

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