Clostridium difficile: Difference between revisions
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==Background==
==Background==
*Most common cause of infectious diarrhea in hospitalized pts
*[[Clostridium]] is a genus of [[Gram-positive bacteria]]
*Most common cause of infectious diarrhea in hospitalized patients
*Use contact isolation if suspect
*Use contact isolation if suspect
*Risk factors for pseudomembranous colitis:
*Alcohol-based hand sanitizers does not reduce spore, but good hand washing does<ref>Leffler DA and Lamont JT. Clostridium difficile Infection. N Engl J Med. 2015; 372:1539-1548.</ref>
**Recent abx use (any)
*60-70% of infants are asymptomatic carriers of c diff<ref>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.</ref>
**GI surgery
**Severe underlying medical illness
**Chemo
**Elderly


==Diagnosis==
===Risk factors (pseudomembranous colitis)===
History
*Recent antibiotic use (any)
*Diarrhea that develops during abx use or w/in 2wk of discontinuation
*GI surgery
*Severe underlying medical illness
*Chemo
*Elderly
 
===Pediatrics===
*Testing in infants < 1 year of age not recommended due to high rates of colonization
**~40% of infants < 1 month are colonized and asymptomatic<ref>Asymptomatic colonization by Clostridium difficile in infants: implications for disease in later life. Jangi S, Lamont JT. J Pediatr Gastroenterol Nutr. 2010 Jul; 51(1):2-7.</ref>
**~15% in infants 6-12 months
**By 2 years of age, normal flora is established, similar to adults<ref>Clostridium difficile Infection in children. Sammons JS, Toltzis P, Zaoutis TE. JAMA Pediatr. 2013 Jun; 167(6):567-73.</ref>
*Risk factors for pediatrics
**Antibiotic exposure, particularly penicillins, cephalosporins, clindamycin, fluoroquinolones
**PPIs
**GI feeding tubes
**Comorbidities - cancer, recent surgery, hospitalizations
 
==Clinical Features==
===History===
*[[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
*Recent discharge from hospital
*Profuse watery diarrhea
*Profuse watery diarrhea
Exam
 
*Abdominal pain
===Exam===
*Fever
*[[Abdominal pain]]
*[[Fever]]
*Leukocytosis
*Leukocytosis
*+Fecal leukocytes (distinguishes from benign forms of abx-induced diarrhea)
*+Fecal leukocytes (distinguishes from benign forms of antibiotic-induced diarrhea)
Labs
 
==Differential Diagnosis==
{{Diarrhea DDX}}
 
==Evaluation==
===Labs===
*C. diff toxin assay
*C. diff toxin assay
**Sn 63-94%, Sp 75-100%
**Sn 63-94%, Sp 75-100%
*Culture
*Culture
**Positve culture only means C. diff present, not necessarily that it is causing disease
**Positive culture only means C. diff present, not necessarily that it is causing disease


===Harbor Testing Algorithm===
===Testing Algorithm===
#Patient with suspected Clostridium difficile associated diarrhea (CDAD)
''For patients with suspected Clostridium difficile associated diarrhea (CDAD)''
##'''Low''' suspicion for CDAD
*'''Low''' suspicion
###Send stool for C. diff toxin assay
**Send stool for C. diff toxin assay
####Positive --> treat (no further testing indicated)
***Positive → treat (no further testing indicated)
####Negative --> do not treat (no further testing indicated)
***Negative → do not treat (no further testing indicated)
##'''High''' suspicion for CDAD
*'''High''' suspicion
###Send stool for C. diff toxin assay AND treat empirically
**Send stool for C. diff toxin assay AND treat empirically
####Positive --> treat (no further testing indicated)
***Positive → treat (no further testing indicated)
####Negative --> Consider discussion with ID (false negative tests may occur); eval for other causes of diarrhea
***Negative → Consider discussion with ID (false negative tests may occur); eval for other causes of diarrhea


*Repeat testing
===Repeat testing===
**Never a need for repeat testing within 7 days of a previous test
*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 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 NEED to repeat test soon after initial negative test (more likely to be a false positive test than a true positive test)


==Treatment==
==Management==
*Mild
===Asymptomatic===
**Either d/c offending abx (if possible) or give metronidazole 500mg PO q6hr x10-14d
*No diagnostic testing or treatment required<ref>Bagdasarian, N, et al. Diagnosis and Treatment of Clostridium difficile in Adults. JAMA. 2015; 313(4):398-408.</ref>
*Moderate
===Mild===
**Metronidazole 500mg PO or IV q6hr x10-14d
*Either discontinue offending antibiotics(if possible) or give [[Metronidazole]] 500mg PO q6hr x10-14d
*Severe
===Moderate===
**Criteria
{{Moderate Cdiff Antibiotics}}
***Age >60yr
===Severe===
***Temp >38.4 (101)
'''Criteria:'''<ref name="IDSA">IDSA Guidelines [http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/cdiff2010a.pdf PDF]</ref><ref>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/</ref>
***Serum albumin <2.5
*Serum lactate levels >2.2 mmol/l
***WBC >15K
*[[Hypotension]] with or without required use of vasopressors
***Pt requires ICU admission
*[[Ileus]] or significant abdominal distention
***Pseudomembranous colitis on endoscopy
*Mental status changes
**Tx
*WBC ≥35,000 cells/mm3 or <2,000 cells/mm3
***[[Vancomycin]] 125-250mg PO q6hr x10d (IV form is not effective)
*Patient requiring ICU admission
***Add metronidazole 500mg IV q6hr if ileus or pt cannot tolerate PO
*End organ failure (mechanical ventilation, renal failure, etc.)
====Management====
{{Severe Cdiff Antibiotics}}
*Emergency colectomy should be considered if:
*Emergency colectomy should be considered if:
**WBC >20K
**WBC >20K
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===Recurrent Infection===
===Recurrent Infection===
#Occurs <=4 weeks after the completion of therapy
*Relapse occurs in 10-25% of patients
##Otherwise consider other (more common) causes
*Occurs <=4 weeks after the completion of therapy
#Antimicrobial resistance is not clinically problematic, first recurrence treated with the same agent used to treat the initial episode
**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 <ref>Melville NA. Rifaximin 'Chaser' Reduces C difficile Recurrent Diarrhea. June 07, 2011. http://www.medscape.com/viewarticle/744157</ref>
*Other options:
**[[IVIG]]
**Fecal transplant
**Fidamoxicin 200mg BID x10 days noninferior to PO vancomycin, and reduces recurrences at 4 weeks after treatment (~15% vs 25%) <ref>Louie TJ et al. Fidaxomicin versus [[Vancomycin]] for Clostridium difficile Infection. N Engl J Med 2011; 364:422-431.</ref>
 
===Pediatrics===
*Stop offending antimicrobial agents, if possible
*Initial occurrence and first recurrence of mild-moderate disease:<ref>D'Ostroph AR and So TY. Treatment of pediatric Clostridium difficile infection: a review on treatment efficacy and economic value. Infect Drug Resist. 2017; 10: 365–375.</ref>
**PO metronidazole 30 mg/kg/d in four divided doses, max 2 g/day
*Severe infection or second recurrence:
**PO vancomycin 40 mg/kg/d in four divided doses, max 500 mg/day
**If no improvement after 24-48 hours, oral vancomycin max dose may be increased to 2 g/d
**Q6hr IV metronidazole, 30 mg/kg/d, may be added to intracolonic/enema vancomycin for ileus, inability to tolerate PO antibiotics
***1-3 year old -- 250 mg vancomycin in 50 mL NS
***4-9 year old -- 375 mg vancomycin in 75 mL NS
***> 9 year old -- 500 mg vancomycin in 100 mL NS
*Multiple recurrences, other strategies, in consult with pediatric GI:
**May benefit from tapering and pulse oral vancomycin over 1.5-2 months, as done in adults
**Consider PO fidaxomicin in ≥ 6 year old patients at 200 mg twice daily for 10 dats
 
===[[Antibiotic Sensitivities]]<ref>Sanford Guide to Antimicrobial Therapy 2014</ref>===
{| class="wikitable"
| align="center" style="background:#f0f0f0;"|'''Category'''
| align="center" style="background:#f0f0f0;"|'''Antibiotic'''
| align="center" style="background:#f0f0f0;"|'''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
|-
| ||[[TMP-SMX]]||X1
|-
| Urinary Agents||[[Nitrofurantoin]]||X1
|-
| ||[[Fosfomycin]]||X1
|-
| Other||[[Rifampin]]||X1
|-
| ||[[Metronidazole]]||'''S'''
|-
| ||[[Quinupristin dalfoppristin]]||I
|-
| ||[[Linezolid]]||I
|-
| ||[[Colistimethate]]||X1
|}


==Disposition==
==Disposition==
*Admit:
*Admit:
**Severe diarrhea
**Severe diarrhea
**Oupt abx failure
**Outpatient antibiotic failure
**Systemic response (fever, leukocytosis, severe abdominal pain)
**Systemic response (fever, leukocytosis, severe abdominal pain)
==Source==
Tintinalli


==See Also==
==See Also==
*[[Diarrhea]]
*[[Diarrhea]]
*[[Clostridium]]
*[[Clostridium]]
==References==
<references/>


[[Category:ID]]
[[Category:ID]]
[[Category:GI]]

Revision as of 13:28, 30 March 2019

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 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

Pediatrics

  • Testing in infants < 1 year of age not recommended due to high rates of colonization
    • ~40% of infants < 1 month are colonized and asymptomatic[3]
    • ~15% in infants 6-12 months
    • By 2 years of age, normal flora is established, similar to adults[4]
  • Risk factors for pediatrics
    • Antibiotic exposure, particularly penicillins, cephalosporins, clindamycin, fluoroquinolones
    • PPIs
    • GI feeding tubes
    • Comorbidities - cancer, recent surgery, hospitalizations

Clinical Features

History

  • 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

Exam

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

Differential Diagnosis

Acute diarrhea

Infectious

Noninfectious

Watery Diarrhea

Traveler's Diarrhea

Evaluation

Labs

  • 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)

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 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

Criteria:[7][8]

  • 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

  • Vancomycin 125 mg PO four times daily for 10 days
  • Fidaxomicin 200 mg PO two times daily for 10 days
  • 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 [9]
  • Other options:
    • IVIG
    • Fecal transplant
    • Fidamoxicin 200mg BID x10 days noninferior to PO vancomycin, and reduces recurrences at 4 weeks after treatment (~15% vs 25%) [10]

Pediatrics

  • Stop offending antimicrobial agents, if possible
  • Initial occurrence and first recurrence of mild-moderate disease:[11]
    • PO metronidazole 30 mg/kg/d in four divided doses, max 2 g/day
  • Severe infection or second recurrence:
    • PO vancomycin 40 mg/kg/d in four divided doses, max 500 mg/day
    • If no improvement after 24-48 hours, oral vancomycin max dose may be increased to 2 g/d
    • Q6hr IV metronidazole, 30 mg/kg/d, may be added to intracolonic/enema vancomycin for ileus, inability to tolerate PO antibiotics
      • 1-3 year old -- 250 mg vancomycin in 50 mL NS
      • 4-9 year old -- 375 mg vancomycin in 75 mL NS
      • > 9 year old -- 500 mg vancomycin in 100 mL NS
  • Multiple recurrences, other strategies, in consult with pediatric GI:
    • May benefit from tapering and pulse oral vancomycin over 1.5-2 months, as done in adults
    • Consider PO fidaxomicin in ≥ 6 year old patients at 200 mg twice daily for 10 dats

Antibiotic Sensitivities[12]

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
TMP-SMX X1
Urinary Agents Nitrofurantoin X1
Fosfomycin X1
Other Rifampin X1
Metronidazole S
Quinupristin dalfoppristin I
Linezolid I
Colistimethate X1

Disposition

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

See Also

References

  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. ↑ Asymptomatic colonization by Clostridium difficile in infants: implications for disease in later life. Jangi S, Lamont JT. J Pediatr Gastroenterol Nutr. 2010 Jul; 51(1):2-7.
  4. ↑ Clostridium difficile Infection in children. Sammons JS, Toltzis P, Zaoutis TE. JAMA Pediatr. 2013 Jun; 167(6):567-73.
  5. ↑ Marx et al. “Cholera and Gastroenteritis caused by Noncholera Vibrio Species”. Rosen’s Emergency Medicine 8th edition vol 1 pg 1245-1246.
  6. ↑ Bagdasarian, N, et al. Diagnosis and Treatment of Clostridium difficile in Adults. JAMA. 2015; 313(4):398-408.
  7. ↑ IDSA Guidelines PDF
  8. ↑ 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/
  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. ↑ D'Ostroph AR and So TY. Treatment of pediatric Clostridium difficile infection: a review on treatment efficacy and economic value. Infect Drug Resist. 2017; 10: 365–375.
  12. ↑ Sanford Guide to Antimicrobial Therapy 2014
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