What percentage of Clostridioides difficile (C. diff) infections present without diarrhea?

How Often Does C. difficile Present Without Diarrhea?

C. difficile infection (CDI) rarely presents without diarrhea, with approximately 16% of cases presenting with atypical manifestations lacking the classic symptom of diarrhea. While diarrhea is the hallmark symptom of CDI, clinicians should be aware that some patients may present with alternative clinical presentations.

Diagnostic Criteria and Atypical Presentations

The diagnosis of CDI typically requires:

1. Presence of diarrhea (defined as ≥3 unformed stools in 24 hours) 1
2. Positive stool test for toxigenic C. difficile or its toxins, or colonoscopic/histopathologic findings demonstrating pseudomembranous colitis 1

However, atypical presentations without diarrhea may include:

• Abdominal pain
• Fever
• Leukocytosis
• Sepsis
• Nausea and vomiting

According to the IDSA/SHEA guidelines, these non-diarrheal presentations accounted for approximately 16% of CDI cases in their analysis, with symptoms including:

• Fever and abdominal pain (4%)
• Nausea and vomiting (2%)
• Abdominal pain (2%)
• Leukocytosis (2%)
• Sepsis (2%)
• Fever alone (1%) 1

Diagnostic Challenges

The absence of diarrhea creates significant diagnostic challenges:

1. Testing limitations: Most diagnostic algorithms are designed for patients with diarrhea, as laboratory testing alone cannot distinguish between asymptomatic colonization and symptomatic infection 1

2. Risk of missed diagnosis: Patients without diarrhea may experience delayed diagnosis, potentially leading to increased morbidity and mortality

3. Colonization vs. infection: Distinguishing between asymptomatic colonization (which can exceed 40% in certain populations) and true infection becomes more difficult without the presence of diarrhea 2

Testing Recommendations

The IDSA/SHEA guidelines emphasize that:

• Testing should be performed only in symptomatic patients 1
• Diagnostic testing should be restricted to unformed stool samples 1
• Testing should not be performed as a "test of cure" as >60% of patients may remain C. difficile positive even after successful treatment 2

Clinical Implications

For patients presenting with suspected CDI but without diarrhea:

• Consider CDI in patients with unexplained leukocytosis, fever, or abdominal pain, particularly those with risk factors (recent antibiotic use, hospitalization, advanced age)
• Maintain a high index of suspicion in patients with risk factors who develop ileus or toxic megacolon without preceding diarrhea
• Place patients with suspected CDI on preemptive contact precautions pending test results if results cannot be obtained on the same day 1

Prevention and Control Measures

Even for patients with atypical presentations:

• Isolate patients with confirmed CDI in private rooms with dedicated toilets 1
• Use gloves and gowns when caring for patients with CDI 1
• Continue contact precautions for at least 48 hours after diarrhea resolves 1

Understanding that CDI can present without diarrhea in approximately 16% of cases is crucial for timely diagnosis and appropriate management, particularly in high-risk populations with recent antibiotic exposure or healthcare facility contact.