CDI stands for Clostridioides difficile infection, a bacterial infection of the large intestine that causes diarrhea, inflammation, and in severe cases, life-threatening complications. It affects roughly 117 per 100,000 people annually in the United States and is the leading cause of antibiotic-associated colitis worldwide.
How CDI Develops
Clostridioides difficile (often called C. diff) is a spore-forming bacterium that thrives in the colon when the normal balance of gut bacteria has been disrupted. Under healthy conditions, the trillions of bacteria already living in your intestines crowd out C. diff and keep it from gaining a foothold. When antibiotics wipe out large portions of that protective community, C. diff can multiply unchecked.
The damage comes from two toxins the bacterium produces, known as toxin A and toxin B. These toxins latch onto cells lining the colon and work their way inside, where they disable proteins that hold the cell’s internal structure together. The result is a chain reaction: cells round up and detach, the tight seals between intestinal cells break apart, and the intestinal lining becomes inflamed and leaky. Both toxins also attract immune cells called neutrophils to the area, which amplifies the inflammation and contributes to the watery diarrhea that defines the infection.
Who Is Most at Risk
Antibiotic use is the single biggest risk factor. Broad-spectrum antibiotics, the kind prescribed to cover a wide range of bacteria, do the most damage to the gut’s protective microbial community. But even targeted antibiotics can open the door to C. diff if they shift the balance enough.
Other factors that raise risk include:
- Age: CDI incidence climbs steadily with age, and people 65 and older face the highest rates of both infection and complications.
- Stomach acid medications: The FDA has flagged proton pump inhibitors (brands like Prilosec, Nexium, and Prevacid) as potentially increasing CDI risk. Acid-reducing drugs called H2 blockers (like Pepcid and Tagamet) are also under review for the same concern.
- Hospitalization and long-term care: Healthcare settings concentrate both C. diff spores and vulnerable patients in one place.
- Chronic medical conditions and weakened immune systems: These reduce the body’s ability to fight off the infection once it takes hold.
Women are affected more often than men, and surveillance data from 2023 shows the highest rates among Native Hawaiian/Pacific Islander individuals and White people compared to other racial and ethnic groups.
Symptoms and Severity
The hallmark symptom is watery diarrhea, typically three or more loose stools per day, often with a distinctive foul smell. Abdominal cramping, low-grade fever, and loss of appetite are common alongside it. In mild cases, symptoms may be limited to diarrhea that resolves with treatment.
Moderate to severe CDI brings more intense inflammation. A condition called pseudomembranous colitis develops in some patients, where yellow-white plaques made of dead cells, immune debris, and a protein called fibrin form on the colon’s inner lining. This is the most common finding when doctors look inside the colon with a scope, and it occurs in about 10% of people with antibiotic-associated diarrhea. In the most severe cases, these plaques cover the entire colon surface, and 3 to 8% of those cases progress to fulminant infection.
When CDI Becomes Dangerous
A small but significant percentage of CDI cases escalate to life-threatening territory. Fulminant C. diff colitis, characterized by dangerously low blood pressure, shock, or a paralyzed bowel, accounts for about 4% of CDI cases and carries an in-hospital mortality rate near 35%.
Toxic megacolon is one of the most feared complications, occurring in roughly 4.3% of CDI patients. The colon dilates beyond 6 centimeters and the patient develops some combination of high fever, rapid heart rate, and signs of systemic collapse like low blood pressure or confusion. Mortality rates for toxic megacolon range from 38 to 80%, and emergency surgery to remove part or all of the colon is often the only option.
How CDI Is Diagnosed
Diagnosis involves testing a stool sample, but a single test isn’t always enough to distinguish active infection from colonization (simply carrying the bacteria without being sick). Most labs use a multi-step approach. The first screen typically checks for a protein that C. diff produces in large quantities, along with a separate test for the toxins themselves. If the protein test is positive but the toxin test is negative, a molecular test that detects the bacterium’s DNA is used to break the tie.
This layered approach matters because molecular tests alone are extremely sensitive and can flag people who carry C. diff in their gut without actually being infected. Detecting the toxin, rather than just the organism, is considered the gold standard for confirming true CDI.
Treatment Options
Current guidelines from both North American and European infectious disease societies place fidaxomicin as the preferred first-line treatment for an initial CDI episode, whether mild or severe. It’s taken by mouth twice daily for 10 days and has a meaningful advantage over older options in preventing recurrence. Vancomycin, taken four times daily for 10 days, remains an acceptable alternative. Metronidazole, once the go-to treatment, is now reserved for situations where neither of the preferred options is available.
For severe cases in patients who are older or immunocompromised, guidelines also recommend a targeted antibody therapy called bezlotoxumab, which neutralizes toxin B and helps reduce the chance of the infection coming back.
Recurrence Is Common
Up to 30% of patients who recover from an initial CDI episode experience a recurrence. The infection returns because antibiotics used to treat C. diff also further damage the gut’s microbial community, leaving the door open for the same cycle to repeat.
Fecal microbiota transplantation (FMT) has become a key tool for breaking this cycle. The procedure delivers a prepared sample of stool from a healthy donor into the patient’s gut, essentially repopulating it with the diverse bacteria needed to keep C. diff in check. In clinical trials, FMT has proven highly effective at preventing further recurrences. Real-world data from a large study of 108 patients showed a 60-day recurrence rate of about 20%, with older patients and those on immune-suppressing medications most likely to relapse after the procedure.
How C. Diff Spreads and Survives
C. diff spreads through its spores, which are shed in the stool of infected individuals and can contaminate surfaces, medical equipment, and the hands of caregivers. These spores are remarkably hardy. They survive on surfaces for more than seven days, resist alcohol-based hand sanitizers, and shrug off many standard hospital disinfectants.
Bleach is the most effective weapon against C. diff spores on surfaces. Studies in hospitals have shown significant reductions in CDI rates after switching from standard disinfectants (quaternary ammonium compounds) to bleach solutions at a concentration of 5,000 parts per million, with a contact time of at least 10 minutes. Adding hydrogen peroxide decontamination on top of bleach cleaning reduces spore counts even further. In healthcare settings, handwashing with soap and water physically removes spores in a way that alcohol gel cannot.