clostridioides%20difficile%20infection
CLOSTRIDIOIDES DIFFICILE INFECTION
Treatment Guideline Chart
Clostridioides (formerly Clostridium) difficile infection is commonly associated with antibiotic treatment and is one of the most common nosocomial infections.
Symptoms usually start on days 2-3 of antibiotic treatment, but may also occur up to 8-12 weeks after discontinuation of antibiotics.
Discontinuation of antibiotics may be the only measure needed for patients with only mild diarrhea, no fever, no abdominal pain nor a high WBC count.
Cessation of antibiotics allows for reconstitution of the normal colonic microflora and markedly reduces risk of recurrence.

Clostridioides%20difficile%20infection Treatment

Principles of Therapy

  • The first step in otherwise healthy patients is to stop the offending antibiotic as soon as possible
    • May be the only measure needed for patients with only mild diarrhea, no fever, no abdominal pain nor a high WBC count
    • Cessation of antibiotics allows for reconstitution of the normal colonic microflora and markedly reduces the risk of recurrence
  • Treatment for C difficile should be started if colitis is evident and diarrhea continues despite discontinuation of precipitating antibiotic
    • If with fulminant C difficile infection and clinical condition deteriorates despite antibiotic therapy, surgical treatment with total abdominal colectomy or a diverting loop ileostomy with colonic lavage is recommended 
  • Antibiotic therapy specific for C difficile should be given to the following:
    • Patients with severe diarrhea or colitis
    • Elderly patients
    • Patients with multiple concomitant illnesses
    • Patients in whom antibiotics cannot be discontinued
  • Empiric antibiotic therapy may be initiated in cases where there is a delay in laboratory confirmation or for patients with fulminant infection 
  • Oral route of administration is preferred because C difficile remains within the lumen of the colon and does not invade the mucosa
  • Other medications that also need to be stopped and avoided include laxatives (to decrease the risk of prolonged diarrhea), opiates and antidiarrheal/anti-peristaltic medications (because impaired intestinal motility can worsen toxin-mediated disease) and unnecessary proton pump inhibitors
  • Asymptomatic toxigenic C difficile colonization requires no treatment

Duration of Therapy

  • Antibiotics are generally given for 10-14 days
    • Normalization of stool consistency and frequency may take weeks after clinical response
  • Prolonged treatment may be necessary for patients with severe colitis or those with underlying gastrointestinal (GI) conditions

Pharmacotherapy

Vancomycin

  • Recent data suggest that Vancomycin is superior to Metronidazole in all cases of C difficile infection
  • 1st-line agent for both non-severe and severe initial cases and for first recurrence in patients previously treated with Metronidazole
  • Oral Vancomycin is poorly absorbed from the intestines which results in high concentrations in the gut lumen along with fewer adverse effects
  • For fulminant cases, it may be given orally or via nasogastric tube with IV Metronidazole 
    • May be administered as retention enema in patients with ileus
  • IV Vancomycin has no effect on C difficile infection as it is not excreted into the colon

Fidaxomicin

  • A treatment option for patients with both non-severe and severe initial cases, for first recurrence in patients previously treated with Vancomycin and for patients with multiple recurrences 
  • As effective as Vancomycin but with fewer secondary recurrences
    • May be given to patients at high risk for recurrence 
  • Has intestinal microbiota-sparing effect
  • May be considered if patient is allergic or intolerant to Vancomycin

Metronidazole

  • No longer recommended as 1st-line agent due to data showing poor rates of initial cure (resolution of diarrhea after 10 days of treatment) and sustained cure (clinical cure and absence of recurrence within 1 month posttreatment)
  • Recommended only if patient is allergic or intolerant to or cannot afford Vancomycin or Fidaxomicin, or if Vancomycin or Fidaxomicin is unavailable 
  • Oral Metronidazole is an alternative agent for non-severe initial cases; IV Metronidazole is used in combination with oral and rectal Vancomycin for fulminant infection 
  • Not to be used in severe or recurrent infection
  • Avoid prolonged or repeated treatment courses due to risk of neurotoxicity 

Other Agents

Teicoplanin

  • As effective as Vancomycin but there is concern regarding the development of resistant enterococcal strains 

Bacitracin (Oral) 

  • Less effective than Vancomycin or Metronidazole
  • Given at 25,000 u PO 6 hourly x 10 days

Cholestyramine, Colestipol

  • Binds C difficile toxins
  • Results of studies have been variable
  • Binds Vancomycin and should therefore not be used concomitantly with this drug

Biologic Agents and Other Therapies

  • Include Ridinilazole, immunoglobulins, monoclonal antibodies (Actoxumab), bacteriophages and probiotics Saccharomyces boulardii, Lactobacillus spp and Bifidobacterium spp 
    • Probiotics appeared to be effective and safe with short-term use together with antibiotics in patients who are not severely debilitated or immunocompromised; may also be an effective adjunct in preventing recurrent infection
    • More studies are needed before these can be recommended

Treatment of Recurrent Infection

  • Mild recurrences often resolve spontaneously and do not require antibiotics
  • For first recurrence, drug previously given may be reused, eg oral Vancomycin or Fidaxomicin
  • For first recurrence in patients initially treated with Vancomycin or in second/subsequent recurrences, give Vancomycin in a tapered and/or pulse regimen
  • For recurrent fulminant disease (regardless if initial or second/subsequent recurrence), treatment is the same as the initial fulminant disease followed by a Vancomycin tapered regimen 
    • If first fulminant C difficile infection episode is not recurrent, complete treatment course without subsequent tapering if patient is improving; if with slow resolution of infection or significant abdominal findings, consider referring to an infectious disease specialist to extend treatment course for >14 days

Other Regimens

  • Vancomycin taper
    • 125 mg PO 6 hourly x 10-14 days, 12 hourly x 1 week, 24 hourly x 1 week, and then every 2 or 3 days x 2-8 weeks
    • Taper inhibits C difficile vegetative cells but preserves colonic flora
  • Vancomycin pulse therapy
    • 125 mg PO every 2 days or 500 mg PO every 3 days x 3 weeks
    • Used for the second recurrence of C difficile infection
  • Vancomycin 125 mg PO 6 hourly x 10 days followed by Rifaximin 400 mg PO 8 hourly x 20 days is a treatment option for patients with multiple recurrences
    • A case series had suggested that Fidaxomicin, instead of Rifaximin, may be given for 20 days 
  • Vancomycin 250-500 mg PO 6 hourly x 10 days followed by S boulardii 500 mg PO 12 hourly x 4 weeks 
  • Metronidazole 500 mg PO 6 hourly x 10 days followed by Cholestyramine 4 g PO 8 hourly + Lactobacillus 1 g PO 6 hourly x 4 weeks
  • Patients with >10 episodes of recurrent diarrhea may need long-term therapy

Bezlotoxumab

  • A human monoclonal antibody which binds to C difficile toxin B that is used to prevent recurrence in high-risk adults receiving antibacterial therapy for C difficile infection 
    • Risk of recurrent C difficile infection is decreased by approximately 40% when given during the first episode 
  • Not an antibacterial drug and thus should only be used in conjunction with C difficile infection antibacterial treatment 
    • May be administered at any time during the 10-14-day antibacterial treatment course

Fecal Microbiota Transplantation or Fecal Bacteriotherapy

  • An effective treatment for recurrent C difficile infection
  • A stool in a liquid suspension is transplanted in the patient’s GI tract
  • May be administered via a nasogastric tube, nasojejunal tube, upper endoscopy, colonoscopy, enema or encapsulated preparations 
  • It restores a healthier intestinal microbiota in patients with recurrent C difficile infection
  • Consider a fecal microbiota transplant in patients with at least 2 recurrences (3 episodes of C difficile infection) who have failed appropriate antibiotic therapy
    • Consult infectious disease and gastroenterology specialists for evaluation

Supportive Therapy

  • Administer fluids and electrolytes to rehydrate and maintain hydration
    • Please see Diarrhea in Adults - Infectious disease management chart for specific therapy
  • Diarrhea may resolve with conservative management in approximately 15-23% of otherwise healthy patients
  • Provide albumin supplementation to all patients with severe infection 
  • Aggressive resuscitation and invasive monitoring may be needed in patients with fulminant colitis
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