Clostridioides difficile infection

CDI occurs when toxigenic Clostridioides difficile multiplies in the colon and produces toxins that injure intestinal cells. The bacterium forms hardy spores that survive for long periods on surfaces and resist many routine disinfectants. Disease most often follows antibiotics that reduce competing gut microorganisms, although community-associated infections can occur without a recent healthcare stay or obvious antibiotic exposure.¹

Important risk factors include older age, hospitalization or residence in a long-term-care facility, previous CDI, immunosuppression, and exposure to broad-spectrum antibiotics such as clindamycin, fluoroquinolones, and later-generation cephalosporins. Gastric-acid suppression and inflammatory bowel disease may also be associated with increased risk, but risk varies with the patient and clinical context.² Colonization without symptoms is common, especially in infants, and does not by itself constitute infection.

The defining clinical problem is new, unexplained diarrhea, often accompanied by abdominal cramping, fever, nausea, or loss of appetite. Severe disease may cause marked abdominal tenderness, dehydration, leukocytosis, kidney injury, hypotension, ileus, or toxic megacolon. Fulminant CDI is a medical emergency because colonic inflammation can progress rapidly to shock and perforation.²

Diagnosis combines compatible symptoms with laboratory testing of an unformed stool specimen. Nucleic-acid amplification tests are highly sensitive but can detect colonization, while toxin immunoassays are more specific for active toxin detection but less sensitive. Many laboratories therefore use a multistep algorithm involving glutamate dehydrogenase, toxin testing, and molecular confirmation. Testing formed stool, asymptomatic people, or repeated samples during the same episode can produce misleading results and is generally discouraged.³

Initial management begins with stopping the inciting antibiotic when clinically feasible, correcting fluid and electrolyte losses, and starting targeted therapy for confirmed or strongly suspected disease. Current specialist guidance generally favors oral fidaxomicin for an initial episode when available, with oral vancomycin as an accepted alternative; treatment choice also depends on severity, access, interactions, and local practice.²

Recurrence is common because treatment may suppress rather than permanently eliminate spores and because the microbiota can remain disturbed. A first recurrence may be treated with fidaxomicin or a vancomycin regimen designed to taper or pulse exposure. Multiple recurrences can prompt specialist use of microbiota-based therapies or fecal microbiota transplantation, which aim to restore colonization resistance. Fulminant disease requires urgent hospital management, high-dose enteral vancomycin with additional therapy in selected cases, surgical consultation, and intensive supportive care.²

Prevention depends more on antibiotic stewardship and environmental control than on routine testing of asymptomatic people. Healthcare facilities reduce transmission through prompt isolation, dedicated equipment, gloves and gowns, careful handwashing with soap and water when appropriate, and sporicidal cleaning of rooms and high-touch surfaces. Alcohol-based hand sanitizer is useful for many organisms but does not reliably remove C. difficile spores from hands.¹

Several details complicate interpretation. Infants frequently carry toxigenic C. difficile without disease, so routine testing in children younger than one year is discouraged. Patients with inflammatory bowel disease may have overlapping symptoms and can experience particularly difficult diagnostic and treatment decisions. Community-associated CDI has also drawn attention because some patients lack the classic hospital and antibiotic history. Vaccines and microbiome-directed prevention strategies remain areas of research rather than standard substitutes for prudent antibiotic use.⁴

Colonization

Presence of an organism without symptoms or tissue damage attributable to it.

Toxin

A bacterial product that damages host cells; toxins A and B are central to CDI pathology.

Fulminant CDI

Severe infection marked by complications such as hypotension, shock, ileus, or toxic megacolon.

Microbiota

The community of microorganisms living in a body site, including the intestine.

Toxic megacolon

Acute dilation of the colon associated with severe inflammation and systemic toxicity.