Clostridium difficile

This page is for adult patients; for pediatric patients see clostridium difficile (peds).


Pseudomembranous colitis with yellow pseudomembranes seen on the wall of the sigmoid colon.
  • 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



Watery Diarrhea

Traveler's Diarrhea


Pseudomembranous colitis from C. difficile on abdominal CT demonstratin diffuse colonic wall thickening and a shaggy endoluminal contour.
Pseudomembranous colitis with (A) Accordion sign in transverse colon (thin arrows). (B) Colonic wall thickness, target sign (thick arrow), peritoneal fluid (thin arrow) and pericolonic fat stranding (arrowhead).


  • 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)
  • 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

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][6]

Severe Fulminant Criteria[7]

  • Hypotension with or without required use of vasopressors
  • Ileus or significant abdominal distention
  • Megacolon



  • No diagnostic testing or treatment required[8]
  • Consider discontinuing offending antibiotics


  • Vancomycin 125 mg PO four times daily for 10 days
  • Fidaxomicin 200 mg PO two times daily for 10 days
  • Metronidazole 500mg PO or IV four times daily for 10 days (third line therapy)


Severe Fulminant

See criteria above (Evaluation section)

  • Vancomycin 500 mg PO or NG four times daily for 10 days
  • Considered rectal instillation of Vancomycin
  • Metronidazole 500 mg IV every 8 hours, particularly if ileus is present.
  • Consider emergency colectomy if:

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 [9]
  • 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%) [10]


  • Admit:
    • Severe diarrhea
    • Outpatient antibiotic failure
    • Systemic response (fever, leukocytosis, severe abdominal pain)

Antibiotic Sensitivities[11]

Category Antibiotic Sensitivity
Penicillins Penicillin G X2
Penicillin V X1
Anti-Staphylocccal Penicillins Methicillin X1
Nafcillin/Oxacillin X1
Cloxacillin/Diclox. X1
Amino-Penicillins AMP/Amox X1
Amox-Clav X1
AMP-Sulb X2
Anti-Pseudomonal Penicillins Ticarcillin X1
Ticar-Clav X1
Pip-Tazo X1
Piperacillin X2
Carbapenems Doripenem X2
Ertapenem X2
Imipenem X2
Meropenem X2
Aztreonam R
Fluroquinolones Ciprofloxacin R
Ofloxacin X1
Pefloxacin X1
Levofloxacin R
Moxifloxacin R
Gemifloxacin X1
Gatifloxacin R
1st G Cephalo Cefazolin X1
2nd G. Cephalo Cefotetan X1
Cefoxitin R
Cefuroxime X1
3rd/4th G. Cephalo Cefotaxime R
Cefizoxime R
CefTRIAXone X1
Ceftaroline X1
CefTAZidime X1
Cefepime R
Oral 1st G. Cephalo Cefadroxil X1
Cephalexin X1
Oral 2nd G. Cephalo Cefaclor/Loracarbef X1
Cefproxil X1
Cefuroxime axetil X1
Oral 3rd G. Cephalo Cefixime X1
Ceftibuten X1
Cefpodox/Cefdinir/Cefditoren X1
Aminoglycosides Gentamicin R
Tobramycin R
Amikacin R
Chloramphenicol I
Clindamycin X1
Macrolides Erythromycin X1
Azithromycin X1
Clarithromycin X1
Ketolide Telithromycin X1
Tetracyclines Doxycycline X1
Minocycline X1
Glycylcycline Tigecycline X1
Daptomycin X1
Glyco/Lipoclycopeptides Vancomycin S
Teicoplanin S
Telavancin S
Fusidic Acid X1
Trimethoprim X1
Urinary Agents Nitrofurantoin X1
Fosfomycin X1
Other Rifampin X1
Metronidazole S
Quinupristin dalfoppristin I
Linezolid I
Colistimethate X1

See Also


  1. Leffler DA and Lamont JT. Clostridium difficile Infection. N Engl J Med. 2015; 372:1539-1548.
  2. Marx et al. “Cholera and Gastroenteritis caused by Noncholera Vibrio Species”. Rosen’s Emergency Medicine 8th edition vol 1 pg 1245-1246.
  3. 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,
  4. IDSA Guidelines PDF
  5. ACG Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections
  6. McDonald LC, et al. 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). Clinical Infectious Diseases. 2018;66:e1.
  7. McDonald LC, et al. 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). Clinical Infectious Diseases. 2018;66:e1.
  8. Bagdasarian, N, et al. Diagnosis and Treatment of Clostridium difficile in Adults. JAMA. 2015; 313(4):398-408.
  9. Melville NA. Rifaximin 'Chaser' Reduces C difficile Recurrent Diarrhea. June 07, 2011.
  10. Louie TJ et al. Fidaxomicin versus Vancomycin for Clostridium difficile Infection. N Engl J Med 2011; 364:422-431.
  11. Sanford Guide to Antimicrobial Therapy 2014