Clostridioides difficile: Difference between revisions

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Clostridioides difficile
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== Background ==
==Background==
=== Microbiology ===
===Microbiology===
⚫
* Spore-forming, anaerobic, Gram-positive bacillus


⚫
*Spore-forming, anaerobic, [[Stain::Gram-positive]] [[Cellular shape::bacillus]]
⚫
=== Risk factors ===
⚫
* Antibiotic exposure, typically broad-spectrum antibiotics especially those with anaerobic coverage[[CiteRef::brown2013me]]
⚫
** Clindamycin
⚫
** Fluoroquinolones (especially with NAP1 strain)
⚫
** Cephalosporins
⚫
** Monobactams
⚫
** Carbapenems
⚫
* PPI use


⚫
===Risk factors===


⚫
*Antibiotic exposure, typically broad-spectrum antibiotics especially those with anaerobic coverage[[CiteRef::brown2013me]]
⚫
== Clinical Manifestations ==
⚫
**Clindamycin
⚫
* Profuse watery diarrhea
⚫
**Fluoroquinolones (especially with NAP1 strain)
⚫
**Cephalosporins
⚫
**Monobactams
⚫
**Carbapenems
⚫
*PPI use


=== Severity ===
=== Pathophysiology ===

* Two toxins
** Toxin A (enterotoxin) causes intestinal secretion and mucosal damage
** Toxin B (cytotoxin) is a virulence factor
* Virulence depends on strain (e.g. NAP1 quite virulent with high risk of severe disease and relapse)
* Spores can persist in GI tract up to 2 to 8 weeks despite treatment

⚫
==Clinical Manifestations==

⚫
*Profuse watery diarrhea

===Severity===
{| class="wikitable"
{| class="wikitable"
! Severity !! Definition[[CiteRef::loo2018as]]
!Severity!!Definition[[CiteRef::loo2018as]]
|-
|-
| Mild || WBC ≤15 AND creatinine ≤1.5 x baseline
|Mild||WBC ≤15 AND creatinine ≤1.5 x baseline
|-
|-
| Severe, uncomplicated || WBC >15 OR creatinine >1.5 x baseline OR hypoalbuminemia
|Severe, uncomplicated||WBC >15 OR creatinine >1.5 x baseline OR hypoalbuminemia
|-
|-
| Severe, complicated || Hypotension OR shock OR ileus OR megacolon
|Severe, complicated||Hypotension OR shock OR ileus OR megacolon
|}
|}


=== Children ===
===Children===
⚫
* Asymptomatic carriage is common in infants (37% at 1 month, decreasing to adult levels of 3-5% by 3 years) [[CiteRef::pediatrics2012cl]]
⚫
** Thought to be related to a lack of the binding target of ''C. difficile'' toxin
⚫
* Clinical disease is rare before 12 to 24 months of age


⚫
*Asymptomatic carriage is common in infants (37% at 1 month, decreasing to adult levels of 3-5% by 3 years) [[CiteRef::pediatrics2012cl]]
⚫
== Management ==
⚫
**Thought to be related to a lack of the binding target of ''C. difficile'' toxin
⚫
*Clinical disease is rare before 12 to 24 months of age

⚫
==Management==
{| class="wikitable"
{| class="wikitable"
! Severity
!Severity
! First-line[[CiteRef::loo2018as]]
!First-line[[CiteRef::loo2018as]]
! Alternatives
!Alternatives
|-
|-
! colspan=3 | Initial episode
! colspan="3" |Initial episode
|-
|-
| Mild to moderate
|Mild to moderate
| [[Vancomycin]] 125 mg po QID for 10-14 days
|[[Vancomycin]] 125 mg po QID for 10-14 days
| [[Fidaxomicin]] 200 mg po BID for 10 days<br/>[[Metronidazole]] 500 mg po TID for 10-14 days
|[[Fidaxomicin]] 200 mg po BID for 10 days<br />[[Metronidazole]] 500 mg po TID for 10-14 days
|-
|-
| Severe, uncomplicated
|Severe, uncomplicated
| [[Vancomycin]] 125 mg po QID for 10-14 days<br/>[[Fidaxomicin]] 200 mg po BID for 10 days
|[[Vancomycin]] 125 mg po QID for 10-14 days<br />[[Fidaxomicin]] 200 mg po BID for 10 days
|
|
|-
|-
| Severe, complicated
|Severe, complicated
| [[Vancomycin]] 125-500 mg po QID for 10-14 days plus [[metronidazole]] 500 mg IV q8h
|[[Vancomycin]] 125-500 mg po QID for 10-14 days plus [[metronidazole]] 500 mg IV q8h
| [[Fidaxomicin]] 200 mg po BID for 10 days plus [[metronidazole]] 500 mg IV q8h<br/>Consider rectal vancomycin if ileus
|[[Fidaxomicin]] 200 mg po BID for 10 days plus [[metronidazole]] 500 mg IV q8h<br />Consider rectal vancomycin if ileus
|-
|-
! colspan=3 | Recurrent episode
! colspan="3" |Recurrent episode
|-
|-
| First recurrence, mild to moderate
|First recurrence, mild to moderate
| [[Vancomycin]] 125 mg po QID for 14 days
|[[Vancomycin]] 125 mg po QID for 14 days
| [[Fidaxomicin]] 200 mg po BID for 10 days
|[[Fidaxomicin]] 200 mg po BID for 10 days
|-
|-
| First recurrence, severe, uncomplicated
|First recurrence, severe, uncomplicated
| [[Vancomycin]] 125 mg po QID for 14 days<br/>[[Fidaxomicin]] 200 mg po BID for 10 days
|[[Vancomycin]] 125 mg po QID for 14 days<br />[[Fidaxomicin]] 200 mg po BID for 10 days
|
|
|-
|-
| Second or subsequent recurrence
|Second or subsequent recurrence
| [[Vancomycin]] as prolonged tapered or pulsed regimen
|[[Vancomycin]] as prolonged tapered or pulsed regimen
| Consider fecal microbiota tranplantation after vancomycin
|Consider fecal microbiota tranplantation after vancomycin
|}
|}


* For '''rectal vancomycin''', add 500 mg to 100 mL normal saline and give as retention enema every 6 hours
*For '''rectal vancomycin''', add 500 mg to 100 mL normal saline and give as retention enema every 6 hours
* A sample '''vancomycin taper''': 125 mg po QID for 14 days, then 125 mg po TID for 7 days, then 125 mg po BID for 7 days, then 125 mg po daily for 7 days, then 125 mg po q2-3d for 2 to 8 weeks
*A sample '''vancomycin taper''': 125 mg po QID for 14 days, then 125 mg po TID for 7 days, then 125 mg po BID for 7 days, then 125 mg po daily for 7 days, then 125 mg po q2-3d for 2 to 8 weeks

⚫
==Further Reading==


⚫
*[https://www.ammi.ca/Content/AMMI%20Canada%20treatment%20practice%20guidelines%20for%20Clostridium%20difficile%20infection%2Epdf AMMI treatment practice guidelines for Clostridium difficile infection 2018]
⚫
== Further Reading ==
⚫
*Clostridioides difficile: diagnosis and treatments. ''BMJ''. 2019;366:l4609. doi: [https://doi.org/10.1136/bmj.l46091 10.1136/bmj.l46091]
⚫
* [https://www.ammi.ca/Content/AMMI%20Canada%20treatment%20practice%20guidelines%20for%20Clostridium%20difficile%20infection%2Epdf AMMI treatment practice guidelines for Clostridium difficile infection 2018]
⚫
* Clostridioides difficile: diagnosis and treatments. ''BMJ''. 2019;366:l4609. doi: [https://doi.org/10.1136/bmj.l46091 10.1136/bmj.l46091]


{{DISPLAYTITLE:''Clostridioides difficile''}}
{{DISPLAYTITLE:''Clostridioides difficile''}}

Revision as of 00:45, 24 August 2020

Background

Microbiology

  • Spore-forming, anaerobic, Gram-positive bacillus

Risk factors

  • Antibiotic exposure, typically broad-spectrum antibiotics especially those with anaerobic coverage1
    • Clindamycin
    • Fluoroquinolones (especially with NAP1 strain)
    • Cephalosporins
    • Monobactams
    • Carbapenems
  • PPI use

Pathophysiology

  • Two toxins
    • Toxin A (enterotoxin) causes intestinal secretion and mucosal damage
    • Toxin B (cytotoxin) is a virulence factor
  • Virulence depends on strain (e.g. NAP1 quite virulent with high risk of severe disease and relapse)
  • Spores can persist in GI tract up to 2 to 8 weeks despite treatment

Clinical Manifestations

  • Profuse watery diarrhea

Severity

Severity Definition2
Mild WBC ≤15 AND creatinine ≤1.5 x baseline
Severe, uncomplicated WBC >15 OR creatinine >1.5 x baseline OR hypoalbuminemia
Severe, complicated Hypotension OR shock OR ileus OR megacolon

Children

  • Asymptomatic carriage is common in infants (37% at 1 month, decreasing to adult levels of 3-5% by 3 years) 3
    • Thought to be related to a lack of the binding target of C. difficile toxin
  • Clinical disease is rare before 12 to 24 months of age

Management

Severity First-line2 Alternatives
Initial episode
Mild to moderate Vancomycin 125 mg po QID for 10-14 days Fidaxomicin 200 mg po BID for 10 days
Metronidazole 500 mg po TID for 10-14 days
Severe, uncomplicated Vancomycin 125 mg po QID for 10-14 days
Fidaxomicin 200 mg po BID for 10 days
Severe, complicated Vancomycin 125-500 mg po QID for 10-14 days plus metronidazole 500 mg IV q8h Fidaxomicin 200 mg po BID for 10 days plus metronidazole 500 mg IV q8h
Consider rectal vancomycin if ileus
Recurrent episode
First recurrence, mild to moderate Vancomycin 125 mg po QID for 14 days Fidaxomicin 200 mg po BID for 10 days
First recurrence, severe, uncomplicated Vancomycin 125 mg po QID for 14 days
Fidaxomicin 200 mg po BID for 10 days
Second or subsequent recurrence Vancomycin as prolonged tapered or pulsed regimen Consider fecal microbiota tranplantation after vancomycin
  • For rectal vancomycin, add 500 mg to 100 mL normal saline and give as retention enema every 6 hours
  • A sample vancomycin taper: 125 mg po QID for 14 days, then 125 mg po TID for 7 days, then 125 mg po BID for 7 days, then 125 mg po daily for 7 days, then 125 mg po q2-3d for 2 to 8 weeks

Further Reading

References

  1. a b  Kevin A. Brown, Nagham Khanafer, Nick Daneman, David N. Fisman. Meta-Analysis of Antibiotics and the Risk of Community-Associated Clostridium difficile Infection. Antimicrobial Agents and Chemotherapy. 2013;57(5):2326-2332. doi:10.1128/aac.02176-12.
  2. ^  Aaron C Miller, Alan T Arakkal, Daniel K Sewell, Alberto M Segre, Joseph Tholany, Philip M Polgreen. Comparison of Different Antibiotics and the Risk for Community-Associated Clostridioides difficile Infection: A Case–Control Study. Open Forum Infectious Diseases. 2023;10(8). doi:10.1093/ofid/ofad413.
  3. a b  Mayan Gilboa, Gili Regev-Yochay, Eyal Meltzer, Ido Cohen, Yovel Peretz, Tal Zilberman-Daniels, Amitai Segev, Sharon Amit, Dafna Yahav, Noam Barda. Antibiotic Use and the Risk of Hospital-Onset Clostridioides Difficile Infection. JAMA Network Open. 2025;8(8):e2525252. doi:10.1001/jamanetworkopen.2025.25252.
  4. ^  Yangxi Liu, Mengfei Dai, Kanghuai Zhang, Li Zhang, Bin Lin, Keyu Chen, Haitao Wang, Zhichun Gu, Yuetian Yu, Yan Wang. Risk of Clostridioides difficile infection following different antibiotics: insights from multi-source medical data. International Journal of Antimicrobial Agents. 2024;64(4):107288. doi:10.1016/j.ijantimicag.2024.107288.
  5. a b  Vivian G Loo, Ian Davis, John Embil, Gerald A Evans, Susy Hota, Christine Lee, Todd C Lee, Yves Longtin, Thomas Louie, Paul Moayyedi, Susan Poutanen, Andrew E Simor, Theodore Steiner, Nisha Thampi, Louis Valiquette. Association of Medical Microbiology and Infectious Disease Canada treatment practice guidelines for Clostridium difficile infection. Official Journal of the Association of Medical Microbiology and Infectious Disease Canada. 2018;3(2):71-92. doi:10.3138/jammi.2018.02.13.
  6. ^   Clostridium difficile Infection in Infants and Children. Pediatrics. 2012;131(1):196-200. doi:10.1542/peds.2012-2992.
  7. ^  Mazen S. Bader, John Hawboldt, Cheryl Main, Dominik Mertz, Mark Loeb, Alison Farrell, Joanna Joyce. Review of high dose vancomycin in the treatment of Clostridioides difficile infection. Infectious Diseases. 2020;52(12):847-857. doi:10.1080/23744235.2020.1800080.
  8. ^  Caio T Heleno, Aleksey Tagintsev, Katharine Lasley, Douglas Summerfield. Fidaxomicin as a Salvage Therapy for Fulminant Clostridioides difficile Infection. Cureus. 2021. doi:10.7759/cureus.16559.
  9. ^  Emma C. Phillips, Cirle A. Warren, Jennie Z. Ma, Gregory R. Madden. Impact of Tigecycline on C. difficile Outcomes: Case Series and Propensity-Matched Retrospective Study. Antimicrobial Agents and Chemotherapy. 2022;66(6). doi:10.1128/aac.00001-22.
  10. ^  Andrew M Skinner, Xing Tan, Benjamin D Sirbu, Larry H Danziger, Dale N Gerding, Stuart Johnson. A Tapered-pulsed Fidaxomicin Regimen Following Treatment in Patients With Multiple Clostridioides difficile Infection Recurrences. Clinical Infectious Diseases. 2021;73(6):1107-1109. doi:10.1093/cid/ciab233.
  11. ^  Hoonmo L. Koo, Diana C. Koo, Daniel M. Musher, Herbert L. DuPont. Antimotility Agents for the Treatment ofClostridium difficileDiarrhea and Colitis. Clinical Infectious Diseases. 2009;48(5):598-605. doi:10.1086/596711.
  12. ^  Steven W Johnson, Shannon V Brown, David H Priest. Effectiveness of Oral Vancomycin for Prevention of Healthcare Facility–Onset Clostridioides difficile Infection in Targeted Patients During Systemic Antibiotic Exposure. Clinical Infectious Diseases. 2019;71(5):1133-1139. doi:10.1093/cid/ciz966.

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