Can Probiotics Prevent C. diff While Taking Antibiotics?

Reducing the risk of C. diff
What probiotics may—and may not—do
Balancing safety with effective Lyme treatment

Many patients prescribed antibiotics worry about developing Clostridioides difficile infection, commonly called C. diff. Research suggests that certain probiotics may reduce the risk of antibiotic-associated C. diff infection, although they do not eliminate the risk and are not appropriate for every patient. Patients being treated for Lyme disease and other tick-borne illnesses often ask whether probiotics can help lower this risk while they complete an appropriate course of antibiotics.

There are an estimated 300,000 new cases of Lyme disease each year in the United States. Because many of these patients require antibiotic therapy to treat Lyme disease and associated tick-borne infections, there is a possibility of developing C. diff infection. However, deciding not to prescribe antibiotics—or stopping treatment too early because of concern over C. diff—may also place patients at risk for persistent or progressive manifestations of Lyme disease.

Patients requiring treatment for Lyme disease, babesiosis, ehrlichiosis, or other tick-borne illnesses sometimes need longer or combination antibiotic regimens, making careful monitoring for gastrointestinal complications particularly important.

Doctors should carefully weigh the risk of acquiring Clostridioides difficile-associated diarrhea against the risk of developing chronic complications from Lyme disease if an appropriate course of treatment is not provided. Published reports indicate that antibiotic therapy for Lyme disease can lead to C. diff infection. One death associated with C. diff infection in a Lyme disease patient has been reported. [1-3]

However, Lyme disease itself can lead to significant long-term health problems if not appropriately treated. Studies have described chronic neurologic Lyme disease, [4] Lyme encephalopathy, [5,6] neuropsychiatric Lyme disease, [7] autonomic dysfunction, [8] and persistent symptoms following treatment. [9]

Clostridioides difficile (formerly Clostridium difficile) is a toxin-producing anaerobic bacterium and remains one of the leading causes of healthcare-associated and community-associated infectious diarrhea. Severe infection may lead to toxic megacolon, septic shock, acute kidney injury, and death if left untreated. [10,11]

Antibiotic exposure is the single most important risk factor because antibiotics disrupt the normal intestinal microbiome, allowing toxin-producing C. diff to proliferate. Certain antibiotics—including clindamycin, fluoroquinolones, cephalosporins, and broad-spectrum penicillins—have historically been associated with a higher risk of C. diff infection. [11]

Treatment options for C. diff infection

Fortunately, effective treatments are available for most patients with C. diff infection. Current guidelines recommend fidaxomicin as the preferred treatment for an initial episode when available, with oral vancomycin remaining an excellent alternative. Fidaxomicin appears to reduce recurrence compared with vancomycin in many patients. [11]

Patients with recurrent infection may benefit from additional therapies such as bezlotoxumab or fecal microbiota-based treatments in selected cases. Approximately 20% of patients experience recurrence after an initial episode, making prevention especially important. [11]

Fecal microbiota transplantation (FMT) has also proven effective for many patients with multiple recurrences of C. diff infection. Earlier studies reported cure rates substantially higher than vancomycin alone for recurrent disease. [12]

Can probiotics help prevent C. diff?

Researchers have investigated whether probiotics can lower the risk of developing C. diff infection while patients are taking antibiotics.

In a large systematic review and meta-analysis, Lau and Chamberlain found that probiotic use significantly reduced the risk of developing C. difficile-associated diarrhea by approximately 60%. Benefits were observed in both children and adults. [10]

Individual probiotic groups—including Lactobacillus, Saccharomyces, and mixed probiotic formulations—were each associated with a reduction in the risk of C. diff-associated diarrhea.

Probiotics are thought to help maintain the normal intestinal microbiome, inhibit colonization by pathogenic bacteria, strengthen the intestinal barrier, and modulate immune responses that help maintain gastrointestinal homeostasis. [10]

What do current guidelines recommend?

Since publication of the 2016 meta-analysis, professional society recommendations have become more cautious. The 2021 American College of Gastroenterology (ACG) guideline does not recommend routine probiotic use for primary prevention of Clostridioides difficile infection in patients receiving antibiotics because probiotic products vary substantially and the overall quality of evidence remains inconsistent. The guideline recommends individualized decision-making based on each patient’s risk factors and clinical circumstances. [13]

More recent reviews similarly conclude that probiotics remain an area of active investigation. While some studies suggest benefit, additional high-quality research is needed to determine which probiotic strains, doses, and treatment durations provide the greatest protection. [11]

How can patients lower their risk of C. diff?

Patients taking antibiotics may be able to reduce their risk by:

• Taking antibiotics only when medically necessary.
• Using the shortest effective antibiotic course.
• Discussing whether a probiotic is appropriate.
• Avoiding unnecessary acid-suppressing medications when possible.
• Washing hands with soap and water after using the bathroom.
• Seeking medical attention promptly for persistent diarrhea, fever, abdominal pain, or dehydration.

Patients with Lyme disease and gastrointestinal symptoms should also be monitored carefully, since diarrhea, abdominal discomfort, and medication-related side effects can overlap with symptoms from infection, antibiotics, or other medical conditions.

Who should avoid probiotics?

Although probiotics are generally well tolerated in healthy individuals, they may not be appropriate for everyone. Patients with severe immunosuppression, central venous catheters, critical illness, or certain other medical conditions should discuss probiotic use with their physician because rare cases of bloodstream infection or fungemia have been reported.

Clinical perspective

In my practice treating Lyme disease, preventing antibiotic complications is always important. At the same time, I also see patients whose Lyme disease became more difficult to treat after antibiotics were stopped prematurely because of concerns about side effects. Treatment decisions should balance both risks and be individualized for each patient.

This is especially important for patients with persistent Lyme disease symptoms or complex tick-borne illness, where the consequences of undertreatment and the risks of antibiotic complications both deserve careful consideration.

Frequently Asked Questions

Do probiotics prevent C. diff infection?

Probiotics may reduce the risk of Clostridioides difficile infection in some patients receiving antibiotics, but they do not completely prevent infection. Earlier meta-analyses found a significant reduction in risk, while more recent professional guidelines recommend individualized decision-making because probiotic products and study results vary.

Which probiotics have been studied for preventing C. diff?

Clinical studies have evaluated several probiotic preparations, including Lactobacillus, Saccharomyces boulardii, and combinations of multiple probiotic strains. No single product has been proven superior for every patient.

Should I take probiotics while taking antibiotics?

Some patients may benefit from probiotics while taking antibiotics, particularly those at higher risk for antibiotic-associated diarrhea. However, probiotics are not appropriate for everyone. Individuals who are immunocompromised or critically ill should discuss probiotic use with their physician before starting treatment.

Can probiotics make C. diff worse?

Probiotics do not usually make C. diff infection worse in otherwise healthy patients, but they are not risk-free. Rare bloodstream or fungal infections have been reported, especially in severely immunocompromised patients, critically ill patients, and patients with central venous catheters.

Can probiotics cure C. diff infection?

No. Probiotics should not be considered a treatment for active C. diff infection. Current guidelines recommend antibiotics such as fidaxomicin or oral vancomycin for treatment. Probiotics, if used, are considered an adjunctive strategy rather than primary therapy.

Does yogurt help prevent C. diff?

Although yogurt contains live cultures, there is insufficient evidence that eating yogurt alone prevents C. diff infection during antibiotic treatment. Commercial probiotic preparations evaluated in clinical trials often contain different organisms and substantially higher concentrations than yogurt.

Clinical Takeaway

Antibiotic-associated Clostridioides difficile infection is an important concern for patients receiving treatment for Lyme disease and other bacterial infections. Current evidence suggests that some probiotics may reduce the risk of C. diff-associated diarrhea, but routine probiotic use is not universally recommended because products and supporting evidence vary.

When antibiotics are medically indicated, the decision should balance the potential risk of C. diff infection against the potential consequences of undertreating Lyme disease. Individualized treatment decisions remain essential.

For patients receiving antibiotics, preventing complications while ensuring appropriate treatment of the underlying infection remains the safest long-term strategy.

Related Articles

Learn more about balancing antibiotic benefits and risks in Lyme disease:

Post-Treatment Lyme Disease Syndrome
Why Lyme Testing Can Be Difficult
Recovery From Lyme Disease
Lyme Disease Symptoms Guide
Lyme Disease Coinfections

References

1. Eppes SC, Childs JA. Comparative study of cefuroxime axetil versus amoxicillin in children with early Lyme disease. Pediatrics. 2002;109(6):1173-1177.
2. Holzbauer SM, Kemperman MM, Lynfield R. Death due to community-associated Clostridium difficile in a woman receiving prolonged antibiotic therapy for suspected Lyme disease. Clin Infect Dis. 2010;51(3):369-370.
3. Nadelman RB, Arlin Z, Wormser GP. Life-threatening complications of empiric ceftriaxone therapy for seronegative Lyme disease. South Med J. 1991;84(10):1263-1265.
4. Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med. 1990;323:1438-1444.
5. Logigian EL, Kaplan RF, Steere AC. Successful treatment of Lyme encephalopathy with intravenous ceftriaxone. J Infect Dis. 1999;180:377-383.
6. Fallon BA, Keilp JG, Corbera KM, et al. A randomized placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70:992-1003.
7. Fallon BA, Nields JA, Parsons B, Liebowitz MR, Klein DF. Psychiatric manifestations of Lyme borreliosis. J Clin Psychiatry. 1993;54:263-268.
8. Kanjwal K, Karabin B, Kanjwal Y, Grubb BP. Postural orthostatic tachycardia syndrome following Lyme disease. Cardiol J. 2011;18:63-66.
9. Crowder LA, Yedlin VA, Weinstein ER, Kortte KB, Aucott JN. Lyme disease and post-treatment Lyme disease syndrome. Public Health. 2014;128:784-791.
10. Lau CS, Chamberlain RS. Probiotics are effective at preventing Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Int J Gen Med. 2016;9:27-37.
11. Markantonis JE, Fallon JT, Madan R, Alam MZ. Clostridioides difficile Infection: Diagnosis and Treatment Challenges. Pathogens. 2024;13(2):118.
12. Cammarota G, Masucci L, Ianiro G, et al. Faecal microbiota transplantation by colonoscopy versus vancomycin for recurrent Clostridioides difficile infection. Aliment Pharmacol Ther. 2015;41:835-843.
13. Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol. 2021;116(6):1124-1147.

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Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.

Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention