What is the recommended treatment for an adult patient diagnosed with Clostridioides difficile (C. diff), specifically considering the use of vancomycin?

Vancomycin Treatment for Clostridioides difficile Infection in Adults

Oral vancomycin 125 mg four times daily for 10 days is the first-line treatment for adult patients with C. difficile infection, regardless of disease severity. 1, 2

Current First-Line Recommendations

The most recent IDSA/SHEA guidelines (2018, updated in clinical practice summaries through 2026) have fundamentally changed the treatment paradigm for CDI:

• Vancomycin 125 mg orally four times daily for 10 days is now recommended as first-line therapy for both non-severe and severe initial CDI episodes 1, 2
• Fidaxomicin 200 mg orally twice daily for 10 days is an equally acceptable first-line option with lower recurrence rates 1, 3
• Metronidazole has been relegated to an alternative option only when vancomycin and fidaxomicin are unavailable 1, 2

This represents a significant departure from older 2015 guidelines that recommended metronidazole for mild-moderate disease 4.

Disease Severity Classification

Treatment selection historically depended on severity, though current guidelines recommend vancomycin regardless:

• Non-severe CDI: White blood cell count ≤15,000 cells/μL AND serum creatinine <1.5 mg/dL 1
• Severe CDI: White blood cell count >15,000 cells/μL OR serum creatinine ≥1.5 mg/dL 1
• Fulminant CDI: Hypotension/shock, ileus, or megacolon 1, 3

Specific Treatment Regimens by Clinical Scenario

Initial Episode (Non-Severe or Severe)

• Vancomycin 125 mg orally four times daily for 10 days 1, 2, 5
• Alternative: Fidaxomicin 200 mg orally twice daily for 10 days 1
• The 125 mg dose is as effective as higher doses (500 mg) and is preferred unless the patient is critically ill 6

Fulminant CDI

• High-dose vancomycin 500 mg orally four times daily (or via nasogastric tube) 1, 2
• PLUS intravenous metronidazole 500 mg every 8 hours 1, 2
• If ileus present: Add vancomycin retention enema 500 mg in 100 mL normal saline every 4-12 hours 1

First Recurrence

• Fidaxomicin 200 mg twice daily for 10 days is preferred 1
• Alternative: Vancomycin 125 mg four times daily for 10 days (if metronidazole was used initially) 1, 3
• Alternative: Vancomycin tapered and pulsed regimen 4, 1

Multiple Recurrences (≥2)

• Vancomycin tapered/pulsed regimen: 125 mg every 6 hours × 1-2 weeks, then 125 mg every 12 hours × 1 week, then 125 mg every 24 hours × 1 week, then 125 mg every 48 hours × 2-8 weeks 4
• Fidaxomicin extended regimen 1
• Vancomycin followed by rifaximin 1
• Fecal microbiota transplantation after at least 2 recurrences (94% resolution rate vs. 31% with vancomycin alone) 4, 1

Critical Management Principles

Essential Actions

• Discontinue inciting antibiotics immediately if clinically feasible 1, 2
• Avoid antiperistaltic agents and opiates entirely—they worsen outcomes and increase complications 1, 2
• Do NOT perform "test of cure" after treatment completion 4, 1, 5

Duration of Therapy

• Standard duration is 10 days 1, 5
• May extend to 14 days if delayed response 1

Why Metronidazole Is No Longer First-Line

The evidence base has shifted dramatically against metronidazole:

• Inferior cure rates: Metronidazole has 2.5-5% lower clinical cure rates compared to vancomycin (NNT 16-40) 2
• Higher treatment failures in severe disease: 76% cure rate with metronidazole vs. 97% with vancomycin in severe CDI 4
• Neurotoxicity risk: Repeated or prolonged courses carry risk of cumulative and potentially irreversible peripheral neuropathy 3, 2
• Should never be used for recurrent CDI 2

Important Caveats and Monitoring

Systemic Absorption Risk

• Clinically significant serum concentrations can occur with oral vancomycin, particularly in patients with inflammatory intestinal disorders 5
• Monitor serum vancomycin levels in patients with renal insufficiency, colitis, or those receiving concomitant aminoglycosides 5

Nephrotoxicity

• Nephrotoxicity can occur during or after oral vancomycin therapy 5
• Risk is increased in patients >65 years of age 5
• Monitor renal function during and after treatment in elderly patients, even those with normal baseline function 5

Vancomycin-Resistant Enterococci (VRE) Risk

• Oral vancomycin prophylaxis increases VRE colonization and environmental contamination 7, 8
• VRE prevalence increases significantly following vancomycin treatment and persists for 6 months 8
• This risk must be weighed against CDI prevention benefits, particularly in prophylactic use scenarios 8

Dose Considerations

• No benefit to doses >125 mg four times daily for non-fulminant disease—higher doses do not improve cure rates, time to cure, or mortality 9, 6
• Higher doses may reduce recurrence rates (trend toward significance) but this requires further study 9

Special Populations

NPO Patients

• IV metronidazole 500 mg every 8 hours 1
• PLUS vancomycin retention enema 500 mg in 100 mL normal saline four times daily 1

Hematologic Malignancy/HSCT Patients

• These patients respond more poorly to both metronidazole and vancomycin (approximately 50% cure rate) 4
• Consider vancomycin prophylaxis (125 mg every 12 hours for up to 7 days after broad-spectrum antibiotic discontinuation) in patients with prior CDI receiving concomitant antibiotics—reduces recurrence from 35% to 5% 10