View source for Clostridioides difficile

==Background==
===Microbiology===

*Spore-forming, [[Cellular respiration::anaerobic]], [[Stain::Gram-positive]] [[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
*[[Chemotherapy]]
*[[Hematopoietic stem cell transplantation]]

===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
*When following antibiotics:
**Risk is highest within two weeks of starting antibiotics until 1 week after stopping antibiotics
**Risk increases with the duration of antibiotics
**Risk depends on the antibiotic used[[CiteRef::brown2013me]]
***High risk: [[clindamycin]], [[fluoroquinolones]], and non-penicillin β-lactams (i.e. [[cephalosporins]], [[monobactams]], and [[carbapenems]])
***Low risk: [[macrolides]], [[trimethoprim-sulfamethoxazole]], and [[penicillins]]
***No risk: [[tetracyclines]]

===Severity===
{| class="wikitable"
!Severity!!Definition[[CiteRef::loo2018as]]
|-
|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) [[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

== Diagnosis ==

* Usually done with either nucleic acid testing for the toxin gene, or with an EIA test for GDH and toxin A/B enzyme
{| class="wikitable"
!Test
!Sensitivity
!Specificity
|-
|GDH immunoassay
|94-96%
|92-95%
|-
|Toxin A/B enzyme immunoassay
|58-83%
|99%
|-
|Parallel GDH and toxin A/B immunoassay
|58-82%
|99.5%
|-
|Toxin B PCR
|91-96%
|96-98%
|}

==Management==
{| class="wikitable"
!Severity
!First-line[[CiteRef::loo2018as]]
!Alternatives
|-
! colspan="3" |Initial episode
|-
|Mild to moderate
|[[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
|-
|Severe, uncomplicated
|[[Vancomycin]] 125 mg po QID for 10-14 days<br />[[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<br />Consider rectal vancomycin if ileus
|-
! colspan="3" |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<br />[[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

=== High Dose Vancomycin ===

* No clear data supporting high-dose vancomycin, even in severe CDAD[[CiteRef::bader2020re]]

=== Tapered-Pulsed Fidaxomicin ===

* Case series suggest it may be helpful, though recurrence rate still up to 40%<ref>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'', Volume 73, Issue 6, 15 September 2021, Pages 1107–1109, https://doi.org/10.1093/cid/ciab233</ref>
* Fidaxomicin 200 mg once daily for 7 days followed by 200 mg fidaxomicin every other day for the remaining 13 doses

==Prevention==

=== Probiotics ===

* Insufficient evidence to recommend for or against

=== Primary Prophylaxis ===

*Prophylaxis with oral [[vancomycin]] 125 mg PO daily continued until 5 days after end of systemic antimicrobials may be beneficial in preventing CDAD in high-risk patients[[CiteRef::johnson2019ef]]
**Included patients with age≥70 years or who were hospitalized in the past 90 days

=== Secondary Prophylaxis ===

* Oral vancomycin is occasionally used as secondary prophylaxis after a recent (within 3 to 12 months) episode of CDAD
* Per the IDSA guidelines, there is insufficient evidence to recommend for or against

==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]
*Clostridioides difficile: diagnosis and treatments. ''BMJ''. 2019;366:l4609. doi: [https://doi.org/10.1136/bmj.l46091 10.1136/bmj.l46091]

{{DISPLAYTITLE:''Clostridioides difficile''}}
[[Category:Gram-positive bacilli]]