Primary, or first, Infection

Because C. diff infection (CDI) is frequently seen in individuals taking antibiotic medications to treat other infections, it is important to stop taking all antibiotics other than those prescribed by the doctor to treat CDI (the doctor will explain which antibiotics to take and which to stop). This is because taking other antibiotics simultaneously as those used to treat CDI can reduce the effectiveness of the antibiotics used for CDI.

Mild to Moderate Disease

Currently, the number of antibiotics that can treat C. diff is limited. For mild to moderate infections, the most common treatments are vancomycin or fidaxomicin, taken by mouth for ten days. If one doesn’t work, you may need to try the other.  For an initial mild- to moderate episode, vancomycin 125 milligrams (mg) four times per day or fidaxomicin 200 mg twice per day for ten days.

If you are at home, it may be tempting to take a medication that stops or slows diarrhea. In the case of C. diff infection, this is not recommended, as it can lead to more severe disease and even sepsis.

Moderate to Severe Disease

If the infection is moderate to severe or does not resolve with antibiotics, your physician may offer other treatments. One includes utilizing an enema so the antibiotic—usually vancomycin—can be introduced directly into the colon. People with C. diff are also encouraged to drink a lot of fluids to help flush out the infection and avoid foods that can cause cramping or diarrhea. A healthy diet may also help rebuild a healthy gut microbiome.

  • For a patient with severe CDI (white blood cell count greater than 15,000, or a serum creatinine great than 1.5 mg/dl, vancomycin 125 milligrams (mg) four times per day or fidaxomicin 200 mg twice per day for ten days.
  • For patients with a fulminant CDI (hypertension or shock, intestinal obstruction, sepsis, or toxic megacolon), vancomycin 500 mg four times per day PLUS metronidazole 500 mg intravenously for ten days.

Recurrent CDI

About 20% to 30% of people who develop a C. diff infection experience a recurrence—and every time someone has a recurrent infection, their risk of having another one increases. Those most likely to have repeat cases are people who:

  • Are over age 65
  • Continue to take other antibiotics while being treated for C. diff infection
  • Have chronic medical conditions

Unlike other types of infections, recurrent C. diff infections don’t occur because the bacterium has become resistant to treatment. Rather, it is because some C. diff spores can survive initial treatment. While your physician may prescribe a new drug, patients are often treated again using the same antibiotic. Your physician may prescribe a longer course or a “taper” by which the antibiotic is taken at longer intervals.

The following antibiotics are typically given for patients with a recurrent CDI:

  • For the first recurrence, the same antibiotics used for the first infection are usually given: vancomycin 125 milligrams (mg) four times per day or fidaxomicin 200 mg twice per day for ten days.
  • For a second recurrence, the following treatments are recommended: Vancomycin by mouth taper or pulse 125 mg 4 times per day for ten days, then rifaximin 400 mg 3 times per day for 20 days or fidaxomicin 200 mg 2 times per day for ten days, or Fecal microbiota transplantation (see below).Note: Fidaxomicin is more expensive than vancomycin. Because of this, the insurance provider may only cover the cost of this antibiotic in certain circumstances (for example, if someone has recurrent CDI even after treatment with vancomycin). If a patient has recurrent CDI, they should ask their doctor to see if fidaxomicin may be right for them.

Microbiome Therapeutics

If antibiotics do not resolve your CDI, you may need microbiome restoration therapy. A disrupted gut microbiome – usually brought on by antibiotics – is a primary reason CDIs do not resolve. Microbiome therapies introduce healthy bacteria into the gut to restore the variety of 

There are currently two FDA-approved microbiome-based treatments available:  

  • Rebyota is the first FDA-approved microbiome-based treatment to prevent recurrent C. diff infection after you’ve already taken antibiotics. REBYOTA is a liquid mix of trillions of live microbes—including Bacteroides—sourced from the stool of qualified human donors. Each dose and donor have been tested and screened to help address product safety. If you need help paying for Rebyota, there are patient assistance programs for which you may be eligible
  • Vowst is the only FDA-approved microbiota-based therapeutic in oral capsules that can help keep C. diff from returning. The VOWST Voyage Support Program offers a range of resources and programs designed to help eligible patients prescribed VOWST access and initiate treatment. The program includes the VOWST Co-Pay Savings Program for eligible, commercially insured patients to help reduce their out-of-pocket costs. Information on the VOWST Voyage Support Program is available at or by calling 888-356-5444.
  • Fecal transplant, or fecal microbiota transplantation (FMT), is a process in which fecal matter, or stool sample, from a healthy donor, is collected, strained, mixed with a sterile salt solution, and placed in a patient with CDI. This is usually performed by colonoscopy, in which a flexible tube is passed through the anus and rectum. Several studies have shown that FMT effectively treats patients with recurrent CDIs.

Other Treatments

The following non-antibiotic options are available for the treatment of CDI:

  • Intravenous immunoglobulin (also called IVIG), a substance that contains antitoxins, has been used to treat some cases of CDI. However, this treatment has many side effects and may not be beneficial in adults, although there is some evidence that it is effective in children.
  • Bezlotoxumab is a human monoclonal antibody directed against C. difficile toxin B, which prevents intestinal damage and colitis. It is used in conjunction with antibiotics.
  • Another option is probiotics, which are live bacteria that do not cause disease but can replace the “good” bacteria that have been eliminated by antibiotics. Although a recent study has shown that using probiotics in adults reduces the risk of CDI, additional data are needed before they can be recommended for CDI.
  • In patients with severe cases, surgery to remove the infected part of the colon might be required. The Centers for Disease Control and Prevention report that surgery is needed in only 1 or 2 of every 100 persons with a CDI.

What Treatment Options Are Expected in the Future?

Continued efforts are being made to develop new treatment options for CDI, including:

  • Narrow-spectrum antibiotics, including CRS3123 and ibezapolstat, are being studied to see how well they treat CDI, without further degrading the gut microbiome.
  • Additional Microbiome-based therapies and products, including VE303. Check out our Clinical Trials page for more information.
  • Vaccines and preventatives are being tested for their ability to prevent (rather than treat) CDI. Some of these new options that are being tested will hopefully get approval from the US Food and Drug Administration (FDA) and will assist doctors in successfully preventing and treating CDIs, which can be quite devastating for both patients and their families.