What are the causes and management of Clostridioides difficile (C. diff) infection in patients without diarrhea?

Causes of C. difficile Infection Without Diarrhea

Clostridioides difficile infection (CDI) can present without diarrhea in patients with severe disease complicated by ileus, which prevents the passage of stool. 1 This presentation is particularly concerning as it can delay diagnosis and treatment, potentially leading to increased morbidity and mortality.

Pathophysiology and Clinical Presentation

When C. difficile infection occurs without diarrhea, it typically manifests as:

• Ileus: Severe bowel dysfunction preventing stool passage
• Toxic megacolon: Extreme colonic dilation with systemic toxicity
• Abdominal distension: Due to decreased bowel motility
• Abdominal pain and cramps: Often severe and diffuse
• Systemic signs: Fever, leukocytosis, elevated serum lactate, and creatinine 1, 2

Risk Factors

The same risk factors for typical CDI apply to non-diarrheal presentations:

1. Host factors 1:

   • Age >65 years
   • Immunodeficiency
   • Comorbidities
   • Inflammatory bowel disease
   • Malnutrition
   • Low serum albumin

2. Exposure to C. difficile spores 1:

   • Hospitalization
   • Long-term care facility residence
   • Community exposure

3. Disruption of normal colonic microbiome 1, 2:

   • Antibiotic exposure (particularly high-risk antibiotics):
     • Clindamycin (adjusted odds ratio: 35.31)
     • Fluoroquinolones (adjusted odds ratio: 30.71)
     • Cephalosporins (adjusted odds ratio: 19.02)
     • Beta-lactam/beta-lactamase inhibitor combinations (adjusted odds ratio: 9.87)
   • Surgery
   • Other medications affecting gut flora

Diagnostic Approach

For patients with suspected CDI without diarrhea:

1. Perirectal swab testing: When stool specimens cannot be obtained due to ileus, perirectal swabs provide an excellent alternative with high sensitivity (95.7%), specificity (100%), positive predictive value (100%), and negative predictive value (99.1%) 1

2. Laboratory testing methods 1, 2:

   • Nucleic acid amplification tests (NAAT) for C. difficile toxin genes
   • Glutamate dehydrogenase (GDH) screening followed by toxin A/B testing
   • Two-step algorithms (GDH screening + toxin testing or NAAT + toxin confirmation)

3. Supporting clinical and laboratory findings:

   • Leukocytosis
   • Elevated serum creatinine
   • Elevated serum lactate
   • Abdominal imaging showing colonic wall thickening or toxic megacolon

Management

For CDI without diarrhea (typically severe or fulminant disease):

1. Discontinue the inciting antibiotic if possible 1, 2

2. Antimicrobial therapy 2:

   • For severe CDI: Oral vancomycin 125 mg four times daily for 10 days
   • For fulminant CDI with ileus: Oral vancomycin 500 mg four times daily plus IV metronidazole 500 mg every 8 hours
   • Consider rectal vancomycin when oral therapy is not possible

3. Surgical consultation for potential intervention in cases of 2, 3:

   • Perforation
   • Systemic inflammation unresponsive to antibiotics
   • Toxic megacolon
   • Severe ileus
   • Before serum lactate reaches critical levels

4. Supportive care:

   • Fluid and electrolyte replacement
   • Albumin supplementation if severe hypoalbuminemia
   • Avoid antiperistaltic agents and opiates

5. For refractory cases:

   • Fecal microbiota transplantation (FMT) has shown 70-90% cure rates in severe and fulminant CDI 2, 3

Prevention and Infection Control

1. Contact precautions for patients with known or suspected CDI 1

2. Hand hygiene with soap and water (alcohol-based sanitizers do not kill C. difficile spores) 1

3. Environmental cleaning with hypochlorite agents or sporicidal products 1

4. Antibiotic stewardship to minimize use of high-risk antibiotics 1, 2

Clinical Pitfalls to Avoid

• Don't miss the diagnosis: CDI without diarrhea can be easily overlooked; maintain high suspicion in at-risk patients with ileus
• Don't delay treatment: Begin appropriate therapy while awaiting confirmatory testing in severely ill patients 2
• Don't rely solely on a single negative test: When clinical suspicion is high, consider additional testing 2
• Don't use metronidazole monotherapy for severe or fulminant cases 2
• Don't perform "test of cure" after treatment completion 2

By recognizing the possibility of CDI without diarrhea and implementing appropriate diagnostic and treatment strategies, clinicians can improve outcomes in this challenging presentation of a common healthcare-associated infection.