Clostridium difficile
This page is for adult patients; for pediatric patients see clostridium difficile (peds).
Contents
Background
- Clostridium is a genus of gram-positive bacteria
- Most common cause of infectious diarrhea in hospitalized patients
- Use contact isolation if suspect
- Alcohol-based hand sanitizers do not reduce spores, but good hand washing does[1]
Risk factors for Pseudomembranous Colitis
- Recent antibiotic use (any)
- GI surgery
- Severe underlying medical illness
- Chemo
- Elderly
Clinical Features
Varies according to severity and intrinsic host factors (immunosuppression, etc.).
- Profuse watery diarrhea
- Usually develops after 7-10 days of antibiotics use or within 2 weeks of discontinuation
- History of risk factor(s) (see Background)
- May report diffuse abdominal pain/cramping
- At the extreme, may present with sepsis secondary to intestinal perforation or toxic megacolon
Differential Diagnosis
Acute diarrhea
Infectious
- Viral (e.g. rotavirus)
- Bacterial
- Campylobacter
- Shigella
- Salmonella (non-typhi)
- Escherichia coli
- E. coli 0157:H7
- Yersinia enterocolitica
- Vibrio cholerae
- Clostridium difficile
- Parasitic
- Toxin
Noninfectious
- GI Bleed
- Appendicitis
- Mesenteric Ischemia
- Diverticulitis
- Adrenal Crisis
- Thyroid Storm
- Toxicologic exposures
- Antibiotic or drug-associated
Watery Diarrhea
- Enterotoxigenic E. coli (most common cause of watery diarrhea)[2]
- Norovirus (often has prominent vomiting)
- Campylobacter
- Non-typhoidal Salmonella
- Enteroaggregative E. coli (EAEC)
- Enterotoxigenic Bacteroides fragilis
Traveler's Diarrhea
Evaluation
Workup
- Consider testing patients with unexplained and new-onset ≥3 unformed stools within 24 hours[3]
- Institutions should have an agreed protocol using a stool toxin test as part of a multistep algorithm (e.g. glutamate dehydrogenase [GDH] plus toxin; GDH plus toxin, arbitrated by nucleic acid amplification test [NAAT])
- or NAAT plus toxin) rather than a NAAT alone for all specimens received in the clinical laboratory when there are no preagreed institutional criteria for patient stool submission (Figure 2) (weak recommendation, low quality of evidence).
- C. diff toxin assay
- Sn 63-94%, Sp 75-100%
- Culture
- Positive culture only means C. diff present, not necessarily that it is causing disease
Testing Algorithm
For patients with suspected Clostridium difficile associated diarrhea (CDAD)
- Low suspicion
- Send stool for C. diff toxin assay
- Positive → treat (no further testing indicated)
- Negative → do not treat (no further testing indicated)
- Send stool for C. diff toxin assay
- High suspicion
- Send stool for C. diff toxin assay AND treat empirically
- Positive → treat (no further testing indicated)
- Negative → Consider discussion with ID (false negative tests may occur); eval for other causes of diarrhea
- Send stool for C. diff toxin assay AND treat empirically
Repeat testing
- Never a need for repeat testing within 7 days of a previous test
- NO NEED to repeat positive tests as symptoms resolve as a “test of cure”
- NO NEED to repeat test soon after initial negative test (more likely to be a false positive test than a true positive test)
Severe Criteria[4][5]
- Serum lactate levels >2.2 mmol/l
- Hypotension with or without required use of vasopressors
- Ileus or significant abdominal distention
- Mental status changes
- WBC ≥35,000 cells/mm3 or <2,000 cells/mm3
- Patient requiring ICU admission
- End organ failure (mechanical ventilation, renal failure, etc.)
Management
Asymptomatic
- No diagnostic testing or treatment required[6]
Mild
- Either discontinue offending antibiotics (if possible) or give metronidazole 500mg PO q6hr x10-14d
Moderate
- Vancomycin 125 mg PO four times daily
- Fidaxomicin 200 mg PO two times daily
- Metronidazole 500mg PO or IV q6hr x10-14d (third line therapy)
Severe
See criteria above (Evaluation section)
- Vancomycin 125-250mg PO q6hr x10d (IV form is not effective)
- Add Metronidazole 500mg IV q6hr if ileus or patient cannot tolerate PO
- Consider emergency colectomy if:
- WBC >20K
- Lactate >5
- Age >75
- Immunosuppression
- Toxic megacolon
- Colonic perforation
- Multi-organ system failure
Recurrent Infection
Relapse occurs in 10-25% of patients
- Occurs <=4 weeks after the completion of therapy
- Otherwise consider other (more common) causes
- 1st recurrence: same agent as used to treat initial episode (antimicrobial resistance is not clinically problematic)
- 2nd recurrence: tapered vancomycin with pulse doses
- 3rd recurrence: PO vancomycin 10-14 days followed immediately by rifaximin "chaser" 400mg TID x20 days [7]
- Other options:
- IVIG
- Fecal transplant
- Fidaxomicin 200mg BID x10 days noninferior to PO vancomycin, and reduces recurrences at 4 weeks after treatment (~15% vs 25%) [8]
Disposition
- Admit:
- Severe diarrhea
- Outpatient antibiotic failure
- Systemic response (fever, leukocytosis, severe abdominal pain)
Antibiotic Sensitivities[9]
See Also
References
- ↑ Leffler DA and Lamont JT. Clostridium difficile Infection. N Engl J Med. 2015; 372:1539-1548.
- ↑ Marx et al. “Cholera and Gastroenteritis caused by Noncholera Vibrio Species”. Rosen’s Emergency Medicine 8th edition vol 1 pg 1245-1246.
- ↑ Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) McDonald CL, et al. Clinical Infectious Diseases, Volume 66, Issue 7, 1 April 2018, Pages e1–e48, https://doi.org/10.1093/cid/cix1085
- ↑ IDSA Guidelines PDF
- ↑ ACG Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections http://gi.org/guideline/diagnosis-and-management-of-c-difficile-associated-diarrhea-and-colitis/
- ↑ Bagdasarian, N, et al. Diagnosis and Treatment of Clostridium difficile in Adults. JAMA. 2015; 313(4):398-408.
- ↑ Melville NA. Rifaximin 'Chaser' Reduces C difficile Recurrent Diarrhea. June 07, 2011. http://www.medscape.com/viewarticle/744157
- ↑ Louie TJ et al. Fidaxomicin versus Vancomycin for Clostridium difficile Infection. N Engl J Med 2011; 364:422-431.
- ↑ Sanford Guide to Antimicrobial Therapy 2014