Clostridium difficile infection medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Guillermo Rodriguez Nava, M.D. [2]; Yazan Daaboul, M.D.

Overview

Treatment is generally recommended for average-risk patients who are symptomatic with positive lab findings for C. difficile infection. For patients with C. difficile risk factors, empiric therapy is recommended for symptomatic patients regardless of lab findings. Medical therapies for C. difficile infection include oral Metronidazole for mild to moderate infection, and oral Vancomycin plus intravenous Metronidazole for severe infection.

Indications for Treatment

Symptomatic vs. Asymptomatic Individuals

• Treatment is recommended only for average-risk, symptomatic patients (usually diarrhea) with positive lab findings (either ELISA or PCR) of C. difficile infection

• In contrast, treatment is not recommended for average-risk, asymptomatic individuals OR patients with diarrhea and negative lab findings (either ELISA or PCR).

Average Risk vs. High Risk Patients

• The negative predictive values of the diagnostic lab tests (either ELISA or PCR) are sufficiently high > 95% for patients among patients with average risk of developing C. difficile infection. Accordingly, empiric therapy is not recommended if diagnostic lab tests yield negative findings among average-risk patients.

• In contrast the negative predictive values of the diagnostic lab tests (either ELISA or PCR) are NOT sufficiently high for patients at high risk of C. difficile infection. Accordingly, empiric therapy is recommended for high risk patients with high pre-test probability even when lab findings yield negative results. Common risk factors for the development of C. difficile infection are history of antibiotic administration within the past 12 weeks, advanced age > 65 years, immunodeficiency, exposure to healthcare facilities, or inflammatory bowel disease.

For more detailed list of C. difficile risk factors, click here

Principles of Antimicrobial Therapy for Clostridium difficile infection

According to the 2013 practice guidelines for the diagnosis, treatment, and prevention of C. difficile infections, the choice of antimicrobial therapy is based on the severity of the clinical disease. Shown below is a table that defines the severity of C. difficile infection based on clinical features and lab findings:

Severity	Criteria
Mild	Diarrhea as the only symptom
Moderate	Raised white cell count but <15,000 cells/mL and serum creatine <1.5 times baseline
Severe	Leucocytosis >15,000 cells/mL OR serum creatinene level >1.5 times baseline or abdominal tenderness and serum albumin < 3 g/dL
Severe complicated	Hypotension or shock, ileus, megacolon, leucocytosis >20,000 cells/mL OR leucopenia <2,000, lactate >2.2 mmol/L, delirium, fever ≥ 38.5 °C, organ failure

▸ Click on the following categories to expand treatment regimens.

Initial episode   ▸  Mild to moderate   ▸  Severe   ▸  Severe complicated Recurrence   ▸  First recurrence   ▸  Second recurrence

Mild to moderate Recommended treatment ▸ Metronidazole 500 mg orally q8h If no improvement in 5-7 days ▸ Vancomycin 125 mg orally q6h Severe Recommended treatment ▸ Vancomycin 125 mg orally q6h Severe complicated Recommended treatment† ▸ Vancomycin 500 mg orally q6h PLUS ▸ Metronidazole 500 mg IV q8h † If ileus present, add Vancomycin 500 mg in 100 mL normal saline per rectum q6h as retention enema. First recurrence Recommended treatment ▸ Same as first episode but stratified by severity Second recurrence Recommended treatment ▸ Vancomycin in tapered and pulsed doses 125 mg 4 times daily for 14 days 125 mg 2 times daily for 7 days 125 mg once daily for 7 days 125 mg once every 2 days for 8 days (4 doses) 125 mg once every 3 days for 15 days (5 doses)

Duration of Antimicrobial Therapy

• Administer antimicrobial therapy for 10-14 days.
• Continue antimicrobial therapy only for 10 days if there is clinical improvement within 5 to 7 days.

Do's

• Suspend other antibiotic therapies during administration of antibiotics to treat C. difficile infection.
• Administer vancomycin to patients with mild-to-moderate disease who are intolerant/allergic to metronidazole and for pregnant/breastfeeding women..
• Deliver supportive care to patients with severe or severe complicated CDI .
• Perform diagnostic abdominal CT scan for patients with worsening diarrhea and/or abdominal pain to rule out C. difficile-associated complications. To learn more about the typical features of CDI on abdominal CT scan, click here
• Request surgical consultation and perform routine pre-surgical work-up for patients suspected to have complicated C. difficile infection. To view indications for surgical management of C. difficile infection, click here.
• Consider fecal microbiota transplant if there is a third recurrence after a pulsed vancomycin regimen.
• Consider vancomycin enema for patients whose oral antibiotic regimen cannot reach a segment of the colon, such as patients with Hartman's pouch, ileostomy, or colon diversion.
• Administer intravenous immunoglobulins for recurrent C. difficile infection only if patient has hypogammaglobulinemia.
• Manage C. difficile infection simultaneously with inflammatory bowel disease (IBD) flare-up among patients with IBD.
• Continue immunosuppressive medications for IBD patients with C. difficile infection.

Don'ts

• Do not administer metronidazole for a second recurrence episode of CDI or for long-term therapy because of the risk of neurotoxicity.

• Do not administer anti-peristaltic agents to treat diarrhea in patients with CDI.
• Do not administer intravenous immunoglobulins for recurrent C. difficile infection, except if patient has hypogammaglobulinemia.
• Do not increase the dose of immunosuppressive medications for IBD patients with untreated C. difficile infection.

Novel Pharmacologic Therapies

• In 2011, fidaxomicin was FDA-approved for the treatment of C. difficile infection.
  • Fidaxomicin is a poorly absorbed, bactericidal, macrocyclic antibiotic that acts against anaerobic, gram-positive bacteria.
  • Fidaxomicin is non-inferior to vancomycin in the treatment of primary C. difficile infection.
  • Fidaxomicin is associated with significantly reduced rate of recurrence compared with vancomycin (15% vs. 25%), except among patients infected with BI/NAP1/027 strain where the recurrence rate is statistically similar between both therapies.

Fecal Bacteriotherapy

• Fecal bacteriotherapy is a procedure related to probiotic research. It has been suggested as a potential cure for C. difficile infection.
• It involves infusion of bacterial flora acquired from the feces of a healthy donor in an attempt to reverse bacterial imbalance responsible for the recurring nature of the infection.

Treatment Regimen

• 1. Pseudomembranous colitis - mild to moderate

• Preferred regimen: Metronidazole 500 mg PO tid for 10-14 days
• Alternative regimen: Vancomycin 125 mg PO qid for 10-14 days
• Note: If significant risk of recurrence: Vancomycin 125 mg PO qid for 10-14 days OR Fidaxomicin 200 mg PO bid for 10 days

• 2. Pseudomembranous colitis - severe

• Preferred regimen: Vancomycin 125 mg PO qid for 10-14 days
• Note: If significant risk of recurrence: Vancomycin 125 mg PO qid for 10-14 days OR Fidaxomicin 200 mg PO bid for 10 days

• 3. Pseudomembranous colitis - severe, complicated

• Preferred regimen: Vancomycin 125-500 mg PO qid for 10-14 days AND Vancomycin 500 mg diluted in 500 ml of saline as enema per rectum q6h AND Metronidazole 500 mg IV q8h
• Note: Consider urgent surgical consult

• 4. Recurrent pseudomembranous colitis

• 4.1 Treatment of first recurrence

• Preferred regimen: same as first episode or Fidaxomicin 200 mg PO bid for 10 days

• 4.2 Treatment of second or subsequent recurrence

• Preferred regimen: Vancomycin 125 mg PO qid for 14 days THEN Vancomycin 125 mg PO tid for 7 days THEN Vancomycin 125 mg PO bid for 7 days THEN Vancomycin 125 mg PO qd for 7 days THEN Vancomycin 125 mg PO q48h for 7 days THEN Vancomycin 125 mg PO q72h for 7 days OR Fidaxomicin 200 mg PO bid for 10 days
• Note: Consider expert consult for fecal microbiota transplantation