Clostridium difficile

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

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

Noninfectious

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)
  • 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]

  • Leukocytosis with a white blood cell count of ≥15000 cells/mL
  • Serum creatinine level >1.5 mg/dL
  • Serum lactate levels >2.2 mmol/l
  • 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.)

Severe Fulminant Criteria[7]

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

Management

Asymptomatic

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

Non-Severe

  • 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

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]

Disposition

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


Antibiotic Sensitivities[11]

Category Antibiotic Sensitivity
PenicillinsPenicillin GX2
Penicillin VX1
Anti-Staphylocccal PenicillinsMethicillinX1
Nafcillin/OxacillinX1
Cloxacillin/Diclox.X1
Amino-PenicillinsAMP/AmoxX1
Amox-ClavX1
AMP-SulbX2
Anti-Pseudomonal PenicillinsTicarcillinX1
Ticar-ClavX1
Pip-TazoX1
PiperacillinX2
CarbapenemsDoripenemX2
ErtapenemX2
ImipenemX2
MeropenemX2
AztreonamR
FluroquinolonesCiprofloxacinR
OfloxacinX1
PefloxacinX1
LevofloxacinR
MoxifloxacinR
GemifloxacinX1
GatifloxacinR
1st G CephaloCefazolinX1
2nd G. CephaloCefotetanX1
CefoxitinR
CefuroximeX1
3rd/4th G. CephaloCefotaximeR
CefizoximeR
CefTRIAXoneX1
CeftarolineX1
CefTAZidimeX1
CefepimeR
Oral 1st G. CephaloCefadroxilX1
CephalexinX1
Oral 2nd G. CephaloCefaclor/LoracarbefX1
CefproxilX1
Cefuroxime axetilX1
Oral 3rd G. CephaloCefiximeX1
CeftibutenX1
Cefpodox/Cefdinir/CefditorenX1
AminoglycosidesGentamicinR
TobramycinR
AmikacinR
ChloramphenicolI
ClindamycinX1
MacrolidesErythromycinX1
AzithromycinX1
ClarithromycinX1
KetolideTelithromycinX1
TetracyclinesDoxycyclineX1
MinocyclineX1
GlycylcyclineTigecyclineX1
DaptomycinX1
Glyco/LipoclycopeptidesVancomycinS
TeicoplaninS
TelavancinS
Fusidic AcidX1
TrimethoprimX1
TMP-SMXX1
Urinary AgentsNitrofurantoinX1
FosfomycinX1
OtherRifampinX1
MetronidazoleS
Quinupristin dalfoppristinI
LinezolidI
ColistimethateX1

See Also

References

  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, https://doi.org/10.1093/cid/cix1085
  4. IDSA Guidelines PDF
  5. 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/
  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. http://www.medscape.com/viewarticle/744157
  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
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