Clostridium difficile

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  • 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 does not reduce spore, but good hand washing does[1]
  • 60-70% of infants are asymptomatic carriers of c diff[2]

Risk factors (pseudomembranous colitis)

  • Recent antibiotic use (any)
  • GI surgery
  • Severe underlying medical illness
  • Chemo
  • Elderly

Clinical Features


  • Diarrhea that develops during antibiotic use or within 2 weeks of discontinuation
  • Usually occurs after 7-10 days of antibiotics, as diarrhea before that time is more often poor tolerance to antibiotic
  • Recent discharge from hospital
  • Profuse watery diarrhea


  • Abdominal pain
  • Fever
  • Leukocytosis
  • +Fecal leukocytes (distinguishes from benign forms of antibiotic-induced diarrhea)

Differential Diagnosis

Acute diarrhea



Watery Diarrhea

  • Enterotoxigenic E. coli (most common cause of watery diarrhea)[3]
  • Norovirus (often has prominent vomiting)
  • Campylobacter
  • Non-typhoidal Salmonella
  • Enteroaggregative E. coli (EAEC)
  • Enterotoxigenic Bacteroides fragilis

Traveler's Diarrhea



  • 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)



  • No diagnostic testing or treatment required[4]


  • Either discontinue offending antibiotics(if possible) or give Metronidazole 500mg PO q6hr x10-14d




  • 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.)


  • Vancomycin 125-250mg PO q6hr x10d (IV form is not effective)
  • Add Metronidazole 500mg IV q6hr if ileus or patient cannot tolerate PO
  • Emergency colectomy should be considered 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
  • Antimicrobial resistance is not clinically problematic, first recurrence treated with the same agent used to treat the initial episode
  • 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
    • Fidamoxicin 200mg BID x10 days noninferior to PO vancomycin, and reduces recurrences at 4 wks after treatment (~15% vs 25%) [8]

Antibiotic Sensitivities[9]

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


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

See Also


  1. Leffler DA and Lamont JT. Clostridium difficile Infection. N Engl J Med. 2015; 372:1539-1548.
  2. Jangi S and Lamon JT. Asymptomatic colonization by Clostridium difficile: implications for disease in later life. J Pediatr Gastroenterol Nutr. 2010; 51(1):2-7.
  3. Marx et al. “Cholera and Gastroenteritis caused by Noncholera Vibrio Species”. Rosen’s Emergency Medicine 8th edition vol 1 pg 1245-1246.
  4. Bagdasarian, N, et al. Diagnosis and Treatment of Clostridium difficile in Adults. JAMA. 2015; 313(4):398-408.
  5. IDSA Guidelines PDF
  6. ACG Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections
  7. Melville NA. Rifaximin 'Chaser' Reduces C difficile Recurrent Diarrhea. June 07, 2011.
  8. Louie TJ et al. Fidaxomicin versus Vancomycin for Clostridium difficile Infection. N Engl J Med 2011; 364:422-431.
  9. Sanford Guide to Antimicrobial Therapy 2014