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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Suspect CDI with >=3 unformed stools in 24 hours plus antibiotic, hospitalization, long-term care, older age, PPI, or immunocompromise risk
- Test only diarrheal stool; colonization is common, so do not test formed stool or asymptomatic patients
- Preferred initial treatment: fidaxomicin; oral vancomycin is an acceptable alternative
- Fulminant CDI = hypotension/shock, ileus, or megacolon; treat with high-dose oral/NG vancomycin plus IV metronidazole, add rectal vancomycin if ileus
- Recurrent CDI: fidaxomicin, vancomycin taper/pulse, bezlotoxumab in high-risk recurrence, or fecal microbiota-based therapy after multiple recurrences
- Infection control: contact precautions, soap-and-water hand hygiene, sporicidal cleaning
Overview
Clostridioides difficile infection is a toxin-mediated colitis that usually follows disruption of normal gut flora by antibiotics. Clindamycin, fluoroquinolones, cephalosporins, carbapenems, and broad-spectrum penicillins are high-risk exposures, but almost any antibiotic can precipitate CDI. Disease ranges from mild watery diarrhea to fulminant colitis with ileus, toxic megacolon, shock, perforation, and death.
Epidemiology
CDI is one of the most important healthcare-associated infections in the United States, although community-associated CDI also occurs. Risk increases with age, hospitalization, long-term care residence, recent antibiotics, gastric acid suppression, inflammatory bowel disease, transplant, chemotherapy, and prior CDI. Recurrence occurs in a substantial minority after initial infection and becomes more likely after each recurrence.
Clinical Features
Symptoms
Watery diarrhea, typically >=3 unformed stools in 24 hours
Lower abdominal cramping, anorexia, nausea, malaise
Fever and marked leukocytosis in severe infection
Profuse diarrhea with dehydration, AKI, or hypotension
Ileus with abdominal distension and minimal diarrhea in fulminant CDI
Symptoms after recent antibiotics, hospitalization, chemotherapy, or long-term care exposure
Signs
Diffuse or lower abdominal tenderness
Fever, tachycardia, hypotension in severe disease
Abdominal distension, peritonitis, or toxic appearance suggests fulminant colitis or perforation
Signs of dehydration: dry mucosa, orthostasis, reduced urine output
Rectal exam may be nonspecific; pseudomembranes are usually seen only on endoscopy
Investigations
First-line
Stool NAAT plus toxin testing strategyNAAT is sensitive but may detect colonization; toxin EIA improves specificity when testing criteria are appropriate
CBC and BMPLeukocytosis and creatinine elevation define severity and guide admission/monitoring
Medication and exposure reviewRecent antibiotics, PPIs, chemotherapy, hospitalization, and prior CDI are key diagnostic clues
Second-line
CT abdomen/pelvisIf severe pain, distension, ileus, toxic megacolon, perforation, or alternative diagnosis is suspected
Abdominal radiographCan show colonic dilation in toxic megacolon or ileus
Albumin and lactateHypoalbuminemia and elevated lactate suggest severe systemic disease
Specialist
Flexible sigmoidoscopy/colonoscopyRarely needed; may show pseudomembranes if stool testing unavailable or ileus prevents stool sample; avoid if perforation risk high
Surgical consultationFulminant CDI, megacolon, peritonitis, perforation, worsening shock, or lactate/WBC escalation despite therapy
1
Initial non-fulminant episode
- Stop the inciting antibiotic when possible
- Fidaxomicin is preferred when available; oral vancomycin is an acceptable alternative
- Avoid antimotility agents in severe or untreated CDI
- Correct dehydration and electrolytes; review need for PPI
2
Fulminant CDI
- Oral or NG vancomycin 500 mg q6h plus IV metronidazole
- Add rectal vancomycin if ileus limits delivery to colon
- Aggressive resuscitation, ICU monitoring, early surgical consultation
- Subtotal colectomy or diverting loop ileostomy with lavage may be needed for refractory shock, megacolon, perforation, or peritonitis
3
Recurrent CDI
- First recurrence: fidaxomicin preferred; vancomycin taper/pulse is acceptable
- Consider bezlotoxumab for recurrence within 6 months or high-risk patients such as age >=65, immunocompromise, or severe CDI
- Multiple recurrences: fecal microbiota transplantation or FDA-approved microbiota-based therapy after appropriate antibiotic courses
4
Infection control
- Contact precautions with gown/gloves; private room when possible
- Soap-and-water hand hygiene preferred during outbreaks or high CDI burden because spores resist alcohol
- Use EPA-registered sporicidal environmental cleaning
- Antimicrobial stewardship reduces CDI risk
Complications
- Fulminant colitis: Shock, ileus, or megacolon
- Toxic megacolon: Colonic dilation with systemic toxicity; perforation risk
- Recurrence: Due to persistent spores and impaired microbiome recovery
- AKI and electrolyte derangement: From severe diarrhea and dehydration
- Death: Highest risk in older adults, leukemoid reaction, high lactate, shock, and delayed surgery
USMLE Step 2 CK Exam Tips
- 1Only test diarrheal stool. Positive NAAT in an asymptomatic patient may be colonization
- 2First-line initial CDI is fidaxomicin if available; oral vancomycin is acceptable. Metronidazole is no longer preferred for routine adults
- 3Fulminant CDI = oral vancomycin plus IV metronidazole; add rectal vancomycin if ileus
- 4Ileus can mean little diarrhea despite life-threatening CDI
- 5Soap and water is tested because C difficile spores resist alcohol hand sanitizer
- 6Toxic megacolon/peritonitis/shock = early surgery, not repeated oral antibiotic trials alone
- 7Do not give loperamide in suspected severe CDI
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