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Clostridium difficile (C. difficile, or C. diff) is a common and usually harmless bacterial infection of the large intestine. It often produces no symptoms or a little bit of watery diarrhea. Paradoxically, however, treatment with antibiotics can fire up a C. difficile infection in the large intestine that can quickly progress to a life-threatening medical condition. Fortunately, most C. difficile infections usually happen in a hospital or healthcare facility, so treatment begins immediately at the first sign of trouble.
What is C. diff?
Clostridium difficile lives inside the large intestine. While it usually is a common and harmless bacteria, antibiotic use can jump-start a C. difficile infection that may rapidly progress to a severe and even life-threatening medical illness called pseudomembranous colitis.
C. difficile is a common bacteria that is found all around us. When infected with C. difficile, the body's immune system and other bacteria colonies in the intestine keep it in check, so most infections are asymptomatic.
Antibiotic treatment can throw off this delicate balance. A long course of antibiotics wipes out many of the bacteria in the gut, including beneficial ones. C. difficile, on the other hand, is more rugged than other bacteria. The active form (the "vegetative" type) is resistant to many antibiotics, such as penicillins, cephalosporins, fluoroquinolones, and clindamycin. Its inactive form called a "spore" is mostly unaffected by antibiotics.
Antibiotic use and hospital stays are the high-risk factors for C. difficile infections. About 3 out of 5 C. difficile infections happen in hospitals, long-term care facilities, or other healthcare facilities.
However, 2 out of 5 C. difficile infections are community-acquired. We can encounter C. difficile everywhere, so other risk factors include:
- Advanced age
- Use of acid-reducing ulcer medications (proton pump inhibitors)
- Cancer chemotherapy
- Chronic kidney or liver disease
- Inflammatory bowel disease
- A compromised immune system
- Malnutrition
Clostridium difficile produces two potent toxins that create many of the symptoms of Clostridium difficile colitis: toxin A and toxin B. Toxin A causes swelling of the intestinal tissues, and toxin B kills cells in the colon. A new, more deadly strain of C. difficile appeared in the United States and Canada in the 1990s. This strain is more virulent and produces 10 times the amount of toxin A and 23 times the amount of toxin B than other strains.
Once an infection takes hold, the C. difficile toxins cause watery diarrhea and intestinal swelling. At this point, the infection is a mild to moderate Clostridium difficile infection, or CDI, or Clostridium difficile-associated disease (CDAD).
As the disease becomes more advanced, the colon becomes coated in a "pseudomembrane," a thick, gray coating of immune cells, dead cells, debris, and fibrous material. This more severe stage of CDI, characterized by severe diarrhea, abdominal pain, and low fever, is called pseudomembranous colitis.
In some cases, the infection can progress rapidly in a few hours or a couple of weeks after the initial symptoms into a life-threatening illness called fulminant CDI. The C. difficile poisons cause the colon to swell to massive proportions—a condition called toxic megacolon. Colon muscles stop moving, and the colon gradually fills with waste. Parts of the colon die. At this point, the only life-saving treatment may be to remove part or all of the colon. This stage is called severe CDI with complications, and the mortality rate is high.
Once the initial infection clears, about 3 out of 10 patients will develop a new C. difficile infection in about two weeks, called recurrent CDI or rCDI. Antibiotics may treat the infection, but they do not always kill bacteria in their spore form. Half of all those who develop a second infection will develop a third infection in a few weeks.
The Centers for Disease Control and Prevention (CDC) estimates that around half a million people in the United States are diagnosed with CDI every year. Of them, about 29,000 will die from the disease within 30 days of the first diagnosis, and 14,000 of these deaths are directly attributable to the infection. Most of the deaths involve people older than 65.
How is C. diff diagnosed?
Healthcare providers are looking for risk factors, clinical systems, and evidence of the bacteria in stools. The clinical symptoms of Clostridium difficile infection are:
- Watery diarrhea with mucus and maybe blood,
- Lower abdominal pain,
- Loss of appetite,
- Low fever, and
- Nausea and vomiting.
Stool samples will be subject to a sequence of tests:
- Antigen test (enzyme immunoassay for glutamate dehydrogenase) uses antibodies to detect a protein on the bacteria's cell wall (glutamate dehydrogenase).
- Toxin B test (enzyme immunoassay for toxin B) looks for the presence of C. difficile toxin B in the stool.
- Polymerase chain reaction (PCR) test (or nucleic acid amplification test) analyzes the blood for the C. difficile genetic material that codes for the two C. difficile toxins. This is the most commonly done test in hospitalized patients.
- Cytotoxin neutralization assay (or cell cytotoxicity assay) cultures the stool sample and infects sample human tissue to prove C. difficile toxins' presence. It is highly accurate but can take two or more days to finish.
In the United States, the clinical practice guidelines of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America (IDSA/SHEA) are only to use a PCR test or use the first two tests immediately and PCR if the test results are contradictory.
The clinical symptoms and tests will be enough for a diagnosis. The doctor will not need to image the colon unless there's a risk of complications. The doctor may examine the colon using a colonoscopy or sigmoidoscopy if the infection is very advanced, and the patient's life is at risk.
C. diff treatment options
Time is of the essence. Healthcare providers cannot predict how fast the infection will progress, so a diagnosis, even a mild CDI, is considered a medical emergency.
Antibiotics
Upon diagnosis, treatment will immediately begin with:
- Immediate treatment with the antibiotics vancomycin, fidaxomicin, or metronidazole
- Termination of any other antibiotic treatment, however, your physician needs to evaluate the risks
- Discontinuation of other medications, such as narcotics, anti-diarrhea medications, or ulcer medications, that make the condition worse
Depending on the severity of the infection, some patients will be put on fluid and electrolyte replacement and isolated from other people.
Surgery
Most cases will resolve with antibiotic therapy. If the infection advances to toxic megacolon, part or all of the colon may have to be surgically removed in a colectomy procedure.
Fecal microbiota transplantation (FMT)
Patients with recurrent CDI might receive fecal microbiota transplantation to recolonize the colon with normal gut bacteria that keep C. difficile in check. Fecal matter taken from a family member will be injected into the patient's colon to recolonize the gut with beneficial bacteria. Fecal transplants have been used to treat recurrent CDI since the 1950s and have a 90% success rate when used with antibiotics.
Probiotics
Some patients with recurrent Clostridium difficile infections may take probiotics or live cultures of beneficial bacteria that will restore a healthy population of bacteria in the gut. Evidence is mixed, however. In the United States, probiotic therapy used alongside antibiotics is not recommended by the Infectious Diseases Society of America (IDSA) or the Society for Healthcare Epidemiology of America (SHEA).
C. diff medications
Antibiotics are the standard of care for the treatment of Clostridium difficile infection. They will be started immediately upon diagnosis.
The patient will also be taken off certain medications that may be contributing to the problem:
- Antibiotics such as penicillins, cephalosporins, fluoroquinolones, and clindamycin,
- Proton-pump inhibitors,
- Narcotics, or
- Diarrhea medications.
Antibiotics
Patients with CDI will immediately receive rectal or oral vancomycin, oral fidaxomicin, or intravenous metronidazole. The intravenous formulation of vancomycin is not used to treat C. difficile infections as it's not secreted into the gut. These are antibiotics that effectively eliminate active C. difficile infections. Rifaximin may also be used.
Patients with recurrent C. difficile infections will receive "pulsed" vancomycin or fidaxomicin. Full doses are administered for a few days, followed by a rest period, and then readministered at full dose, followed by a rest. Antibiotics do not kill C. difficile spores, so the goal is to kill the spores when they germinate.
A new experimental antibiotic, ridinilazole, is designed to kill only C. difficile while leaving other gut bacteria alone. The drug is in the third phase of clinical trials and looks promising.
Antibodies
The body produces antibodies to the C. difficile toxins that neutralize their poisonous effects. The drug bezlotoxumab is a synthetic antibody that neutralizes C. difficile toxin B and protects colon tissues. It is prescribed along with antibiotics for patients with recurrent C. difficile infections.
What is the best medication for C. diff?
Drug treatment for Clostridium difficile colitis is limited to a few antibiotics: vancomycin, fidaxomicin, and, less commonly, metronidazole and rifaximin. Vancomycin (oral) and fidaxomicin are equally effective at resolving the infection, while fidaxomicin treatment reduces the risk of recurrent C. difficile infections. Metronidazole (oral) is the least effective at fighting off C. difficile, but if the large intestine muscles stop contracting, oral antibiotics such as oral vancomycin or fidaxomicin aren't useful. Physicians follow a protocol when deciding which antibiotic to use. They will also tailor the prescription to the patient's history of sensitivity to antibiotics.
| Best medication for C. diff | ||||
|---|---|---|---|---|
| Drug Name | Drug Class | Administration Route | Standard Dosage | Common Side Effects |
| Vancocin (vancomycin) | Antibiotic | Oral, enema | 4, 125 mg capsules every 6 hours | Nausea, abdominal pain, fever |
| Metronidazole | Antibiotic | Intravenous | Dose depends on weight and is administered every 6 hours | Nausea, headache, abdominal pain |
| Dificid (fidaxomicin) | Antibiotic | Oral | 1, 200 mg tablet twice daily | Nausea, vomiting, abdominal pain |
| Zinplava (bezlotoxumab) | Monoclonal antibody | Oral | 1 injection, dose determined by weight at the beginning of antibiotic therapy | Nausea, fever, headache |
Many of the standard dosages above are from the U.S. Food and Drug Administration (FDA). Dosage is determined by your doctor based on your medical condition, response to treatment, age, and weight. Other possible side effects exist. This is not a complete list.
What are the common side effects of C. diff medication?
Different classes of medications have different side effects. However, this is not a complete list, and you should consult with a healthcare professional for possible side effects and drug interactions based on your specific situation.
Oral antibiotics typically can cause upset stomach, intestinal problems, nausea, and loss of appetite. Vancomycin has a high incidence of serious side effects, such as kidney damage (1 in 20 patients), hearing loss, and anaphylaxis (a dangerous drop in blood pressure). For this reason, physicians prescribe it only for the most severe infections, like C. difficile. Fidaxomicin, too, can cause serious side effects such as megacolon, gastrointestinal bleeding, and high blood sugar. Sensitivity reactions are always a significant concern with antibiotics. At least 1 in 15 people have allergies to one or more antibiotics, and these allergies could be life-threatening.
Monoclonal antibodies (MAB) are relatively safe. Their most serious side effect is typically immunogenicity—when the body gradually develops antibodies to the drug that eventually renders it therapeutically useless.
What is the best home remedy for C. diff?
Antibiotics treat Clostridium infections, but home remedies are necessary to manage the symptoms and prevent complications like dehydration. Drinking plenty of fluids rich in electrolytes and carbohydrates, and eating highly nutritious, easily digested food are helpful.
Using probiotics to restore a healthy bacteria colony in the gut may seem like a logical home remedy, but if you're on antibiotics, the "good" bacteria cultures in the probiotics will be killed off. It may take a few days after the end of antibiotic exposure before probiotics can survive in the gut.
You mustn't spread the infection. In a hospital, patients with C. diff infections are usually isolated to prevent infecting others. For mild or moderate cases of Clostridium infection treated at home, infection control and contact precautions are paramount:
- Follow proper hand hygiene, wash your hands regularly, and make sure to wash them after using the toilet.
- Only chlorhexidine soap or hypochlorous acid hand sanitizer can kill C. diff spores on your hands. Alcohol and soap do not kill the spores.
- If possible, do not share a bathroom with other people.
- Clean surfaces of the home with bleach or chlorhexidine mixed with water.
- If you can, wash linens, towels, and clothes in bleach. If not, soak them in the hottest water possible.
Frequently asked questions about C. diff
Can C. diff go away on its own?
Asymptomatic Clostridium difficile infections usually go away on their own without even being noticed. When a C. diff infection does become symptomatic, research has shown that 1 in 5 infections will resolve without medications. The danger is that C. difficile colitis can rapidly and unpredictably become a medical emergency. Seek medical care at the first signs of infection.
Can C. diff be treated naturally?
Scientists are taking a serious look at natural treatments for Clostridium difficile infections. Medical science has only a limited set of antibiotics they can use against C. diff, and healthcare professionals are worried that they will someday come up against a C. diff strain that isn't treatable with antibiotics. Unfortunately, no herbal or traditional medical treatment can reduce C. diff infections.
What foods should be avoided with C. diff?
As with any condition involving diarrhea, like Clostridium difficile, your diet should be focused on fluids, electrolytes, nutrients, and energy. The secondary goal is not to irritate the gastrointestinal system any more than necessary. Liquids, salts, starchy foods, high nutrient foods, bland foods, and easy-to-digest foods should be on the menu. Avoid the opposite: meats, fats, junk food, spicy foods, acidic foods, and anything else that might cause stomach upset or gas.
What is the first-line treatment for C. diff?
Antibiotics are the first-line treatment for a Clostridium difficile infection. Healthcare providers have only a limited arsenal of antibiotics they can use, starting with vancomycin or fidaxomicin. In some cases, however, the colon muscles stop working, and oral or rectal antibiotics become useless. Neither vancomycin nor fidaxomicin can get into the gut if given intravenously. The only antibiotic left is intravenous metronidazole, which is less effective than either vancomycin or fidaxomicin.
What is the best medication for C. diff?
Vancomycin and fidaxomicin are the most effective antibiotics against Clostridium difficile infections. They are both equally effective at wiping out an initial infection. However, patients treated with fidaxomicin have a lower rate of a recurrent C. diff infection (about 15%) versus patients treated with vancomycin (about 25%). Long-term treatment with vancomycin also runs the risk of kidney damage (about 5% of patients) and hearing loss.
What probiotics kill C. diff?
Probiotics do not kill Clostridium difficile. Probiotics are "good" bacteria and fungi that colonize the intestines and do things that promote intestinal health. They compete with C. difficile bacteria, and some probiotics, such as Lactobacillus or Saccharomyces boulardii, also produce chemicals that prevent other bacteria from growing. Scientists call this "colonization resistance." Along with the immune system, colonization resistance keeps C. diff in check. However, probiotics are not an effective treatment against a primary C. diff infection.
How do you treat C. diff at home?
Home treatment for Clostridium difficile should support the antibiotic therapy, maintain sufficient fluids and electrolytes in the body, provide the body with nutrition and energy, and prevent anyone else in the home from being infected.
How long does it take to recover from C. diff?
A mild or moderate Clostridium difficile infection typically takes 10 to 14 days of antibiotic treatment to clear up. Depending on the antibiotic used to treat the initial infection, about 15% to 25% of patients will develop a second C. diff infection about two weeks after the first one clears up. It's essential to realize this. Many patients develop a second C. diff infection and believe they have come down with something else. They let it go too long and end up in the hospital. Recurrent C diff infection may require several weeks of "pulsed" antibiotic therapy or fecal microbiota transplantation to resolve.