What are the management and treatment options for an older adult patient at risk of Clostridioides (C.) difficile infection with recent antibiotic use or hospitalization?

C. difficile Infection: Risk Factors and Management

Risk Factors for CDI

Advanced age is one of the most important risk factors for C. difficile infection, along with antibiotic exposure, which is the single most modifiable risk factor. 1

Primary Risk Factors

• Antibiotic exposure is the most critical modifiable risk factor, with risk increasing 7- to 10-fold during therapy and in the first month after cessation 1
• High-risk antibiotic classes include:
  • Third-/fourth-generation cephalosporins 1
  • Fluoroquinolones 1
  • Carbapenems 1
  • Clindamycin 1
  • Beta-lactam/beta-lactamase inhibitor combinations 1
• Even single-dose surgical antibiotic prophylaxis increases colonization and symptomatic disease risk 1
• Risk persists for 3 months following antibiotic cessation, with highest risk in the first month 1

Patient-Specific Risk Factors

• Advanced age serves as a surrogate for severity of illness and comorbidities 1
• Hospitalization duration increases daily risk of C. difficile acquisition 1
• Immunocompromised states including:
  • Solid organ transplant recipients 1
  • Cancer patients receiving chemotherapy 1
  • HIV/AIDS patients with CD4 counts <200/mm³ 1
• Inflammatory bowel disease (AmOR 5.13) 1
• Chronic kidney disease (AmOR 12.12) 1
• Cardiac disease (AmOR 4.87) 1
• Proton pump inhibitor use is epidemiologically associated with increased CDI risk 1, 2

Recurrence Risk Factors

• Prior CDI episode (approximately 25% experience recurrence) 1
• Continued use of non-C. difficile antibiotics after CDI diagnosis (OR 4.23) 1
• Concomitant antacid medications (OR 2.15) 1
• Older age (OR 1.62) 1
• Defective humoral immune response against C. difficile toxins 1

Management Approach

Initial Assessment and Diagnosis

Testing should be performed in patients with three or more unformed stools in 24 hours, particularly with recent antibiotic exposure or healthcare-associated diarrhea. 3

• Use two-step testing algorithm: GDH screening followed by toxin testing, or NAAT followed by toxin confirmation 3
• Single toxin EIA alone is insufficient due to poor sensitivity 3
• Consider diagnosis if antibiotics or chemotherapy received within 4-6 weeks 3

Immediate Management Steps

Discontinue the causative antibiotic immediately if clinically feasible, as continued antibiotic use significantly increases recurrence risk. 3

• Absolutely contraindicated: Antiperistaltic agents (loperamide) - they worsen disease severity, mask symptoms, and precipitate toxic megacolon 3
• If symptomatic management needed, use opioids or octreotide as alternatives 3
• If continued antibiotic therapy required for primary infection, switch to agents less implicated in CDI:
  • Parenteral aminoglycosides 1
  • Sulfonamides 1
  • Macrolides 1
  • Vancomycin 1
  • Tetracycline/tigecycline 1

Antibiotic Treatment for Initial Episode

For initial CDI episodes, fidaxomicin is preferred over vancomycin to improve sustained response and reduce recurrence rates. 1

First-Line Options:

1. Fidaxomicin 200 mg orally twice daily for 10 days (preferred) 1, 4

   • Reduces recurrence rates compared to vancomycin 1
   • Similar initial clinical cure rates but superior sustained response 1
   • Can be taken with or without food 4
   • Cost may be prohibitive ($4,871 per 20-tablet package), but patient-assistance programs available 1

2. Vancomycin 125 mg orally four times daily for 10 days (acceptable alternative) 3

   • Clinical success rate approximately 81% 3
   • First-line if fidaxomicin unavailable 1

3. Metronidazole should be limited to mild-moderate CDI in younger patients with few risk factors for recurrence 5

   • Not recommended for long-term therapy due to cumulative neurotoxicity risk 1

Treatment for Recurrent CDI

For first recurrence, fidaxomicin (standard or extended-pulsed regimen) is preferred over standard vancomycin course. 1

First Recurrence Options:

1. Fidaxomicin (preferred) - subsequent recurrence rate 19.7% vs 35.5% with vancomycin 1
2. Vancomycin tapered and pulsed regimen (if vancomycin used initially) 1:
   • 125 mg four times daily for 10-14 days
   • Then 125 mg twice daily for 1 week
   • Then 125 mg once daily for 1 week
   • Then 125 mg every 2-3 days for 2-8 weeks 1
3. Vancomycin standard course (if metronidazole used initially) 1

Multiple Recurrences (≥2 episodes):

1. Vancomycin tapered and pulsed regimen 1
2. Vancomycin followed by rifaximin 400 mg three times daily for 20 days (recurrence rate 15% vs 31% placebo) 1
3. Fidaxomicin (limited evidence for multiply recurrent CDI) 1
4. Fecal microbiota transplantation - strong recommendation for patients failing appropriate antibiotic treatments 1

Severe or Fulminant CDI

For hospitalized patients with severe or fulminant CDI not responding to antibiotics within 2-5 days, conventional FMT should be considered. 1

• Severe CDI: leukocyte count ≥15 × 10⁹ cells/L and/or creatinine ≥1.5 mg/dL 1
• Fulminant CDI: severe disease with shock, ileus, or megacolon 1
• Vancomycin 125 mg orally four times daily (up to 500 mg in fulminant cases) 1
• FMT via colonoscopy or flexible sigmoidoscopy (not nasoenteric tube due to aspiration risk) 1
• Requires multidisciplinary care including critical care, surgery, gastroenterology, and infectious disease 1
• Most patients require repeat FMT every 3-5 days based on response 1

Special Populations

Immunocompromised Patients:

• Mildly/moderately immunocompromised: FMT suggested after standard antibiotic therapy 1
• Severely immunocompromised (active cytotoxic therapy, neutropenia, CD4 <200/mm³): FMT not recommended 1
• Fidaxomicin spores live-brpk or fecal microbiota live-jslm have insufficient evidence in immunocompromised patients 1

IBD Patients:

• Test only if increased diarrhea or new symptoms (high asymptomatic colonization rates) 1
• Maintain ongoing immunosuppression; avoid escalation 1
• Early surgical consultation for severe disease 1
• Consider colectomy with rectal preservation for severely ill patients 1

Adjunctive Therapies

Bezlotoxumab (monoclonal antibody against toxin B) may prevent recurrences in high-risk patients, particularly those with 027 strain, immunocompromised status, or severe CDI. 1

Infection Control Measures

Handwashing with soap and water is mandatory - alcohol-based sanitizers do not inactivate C. difficile spores. 3

• Mechanical removal through friction and running water is the only effective hand hygiene method 3
• Contact precautions for hospitalized patients 1
• Environmental decontamination important due to spore persistence 1

PPI Management

Discontinue PPIs if no clear indication exists, as they are associated with increased CDI risk and recurrence. 2

• Evaluate necessity of PPI therapy 2
• If legitimate indication exists, use minimum effective dose 2
• Consider temporary discontinuation during acute CDI treatment if clinically feasible 2
• Stewardship activities to discontinue unneeded PPIs are strongly warranted 1, 2

Common Pitfalls to Avoid

• Never use antiperistaltic agents - they trap toxins against colonic wall causing deeper tissue damage 3
• Do not use metronidazole for recurrent CDI or long-term therapy 1
• Do not rely on single toxin EIA testing alone 3
• Do not delay surgical consultation in severe/fulminant cases 1
• Do not use FMT in severely immunocompromised patients 1
• Avoid testing asymptomatic patients or those without diarrhea 3