Clostridioides difficile: Difference between revisions

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

References

^ 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.
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.
^ Clostridium difficile Infection in Infants and Children. Pediatrics. 2012;131(1):196-200. doi:10.1542/peds.2012-2992.

@@ Line 1: / Line 1: @@
-== 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"
-! 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"
-! 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''}}