Is it possible to have Clostridioides difficile (C. difficile) infection without fever?

C. difficile Infection Can Occur Without Fever

Yes, C. difficile infection can definitely occur without fever, as fever is not a required symptom for diagnosis and many patients with C. difficile infection present without fever. 1

Clinical Presentation of C. difficile Infection

C. difficile infection (CDI) presents with a spectrum of symptoms that may or may not include fever:

Common Presentations

• Diarrhea (defined as more than two stools per day that conform to the container) is the most common presentation 1
• Abdominal pain
• Leukocytosis (elevated white blood cell count)

Atypical Presentations

• Some patients, especially postoperative patients, may present with:
  • Ileus
  • Toxic megacolon
  • Leukocytosis without diarrhea 1
  • In these cases, diarrhea may not be present at all

Diagnostic Considerations

When evaluating a patient with suspected C. difficile infection but no fever:

1. Focus on the presence of diarrhea (>2 stools per day that conform to the container) as the primary symptom 1
2. Consider CDI in any patient with diarrhea who has received antibiotics within the previous 8-12 weeks 1
3. Look for risk factors:
   • Recent antibiotic exposure (particularly high-risk antibiotics like fluoroquinolones, third/fourth-generation cephalosporins, carbapenems, and clindamycin)
   • Advanced age
   • Prolonged hospitalization
   • Immunocompromised status
   • Inflammatory bowel disease 1

Special Populations

Inflammatory Bowel Disease (IBD) Patients

• IBD patients have a significantly higher risk of CDI (approximately 5 times more likely) 1
• CDI should be considered at every disease flare in IBD patients, especially those on immunosuppressive therapy 1
• The clinical presentation of an IBD exacerbation and CDI often overlap and may be indistinguishable 1

Immunocompromised Patients

• Solid organ transplant recipients, cancer patients, and HIV/AIDS patients have increased risk of CDI 1
• These patients may have atypical presentations due to altered immune responses

Diagnostic Testing

For patients with suspected CDI but no fever:

1. Test a single diarrheal stool specimen (a sample that takes the shape of the container) 1
2. Use a two-step algorithm:
   • Start with a highly sensitive test such as glutamate dehydrogenase (GDH) antigen enzyme immunoassay or nucleic acid amplification test (NAAT)
   • Follow with a second test with high specificity, such as toxin A/B enzyme immunoassays 1

Common Pitfalls

1. Waiting for fever to develop before testing: Absence of fever should not delay testing for C. difficile in patients with appropriate risk factors and diarrhea
2. Over-reliance on clinical signs: Some patients, especially postoperative patients, may present with ileus or toxic megacolon without diarrhea 1
3. Missing CDI in IBD patients: The overlap of symptoms between IBD flares and CDI requires a high index of suspicion 1
4. Inadequate specimen collection: The optimal specimen is a diarrheal stool sample; if this cannot be collected promptly, a rectal swab may be used 1

By recognizing that fever is not a required symptom for CDI diagnosis, clinicians can avoid delays in diagnosis and treatment, potentially improving patient outcomes.