Clostridioides difficile: Difference between revisions
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Clostridioides difficile
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==Background== |
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===Microbiology=== |
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* |
*Spore-forming, [[Cellular respiration::anaerobic]], [[Stain::Gram-positive]] [[Shape::bacillus]] |
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===Risk factors=== |
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*Antibiotic exposure, typically broad-spectrum antibiotics especially those with anaerobic coverage[[CiteRef::brown2013me]] |
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 |
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**[[Clindamycin]] |
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**[[Fluoroquinolones]] (especially with NAP1 strain) |
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**[[Cephalosporins]] |
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**[[Monobactams]] |
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**[[Carbapenems]] |
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*[[PPI]] use |
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*[[Chemotherapy]] |
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*[[Hematopoietic stem cell transplantation]] |
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===Pathophysiology=== |
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== Further Reading == |
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*Two toxins |
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* [https://www.ammi.ca/Content/AMMI%20Canada%20treatment%20practice%20guidelines%20for%20Clostridium%20difficile%20infection%2Epdf AMMI treatment practice guidelines for Clostridium difficile infection 2018] |
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**Toxin A (enterotoxin) causes intestinal secretion and mucosal damage |
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* Clostridioides difficile: diagnosis and treatments. ''BMJ''. 2019;366:l4609. doi: [https://doi.org/10.1136/bmj.l46091 10.1136/bmj.l46091] |
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**Toxin B (cytotoxin) is a virulence factor |
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*Virulence depends on strain (e.g. NAP1 quite virulent with high risk of severe disease and relapse) |
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*Spores can persist in GI tract up to 2 to 8 weeks despite treatment |
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==Clinical Manifestations== |
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*Profuse watery diarrhea |
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*When following antibiotics: |
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**Risk is highest within two weeks of starting antibiotics until 1 week after stopping antibiotics |
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**Risk increases with the duration of antibiotics |
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**Risk depends on the antibiotic used[[CiteRef::brown2013me]] |
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***High risk: [[clindamycin]], [[fluoroquinolones]], and non-penicillin β-lactams (i.e. [[cephalosporins]], [[monobactams]], and [[carbapenems]]) |
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***Low risk: [[macrolides]], [[trimethoprim-sulfamethoxazole]], and [[penicillins]] |
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***No risk: [[tetracyclines]] |
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===Severity=== |
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{| class="wikitable" |
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!Severity!!Definition[[CiteRef::loo2018as]] |
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|- |
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|Mild||WBC ≤15 AND creatinine ≤1.5 x baseline |
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|- |
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|Severe, uncomplicated||WBC >15 OR creatinine >1.5 x baseline OR hypoalbuminemia |
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|- |
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|Severe, complicated||Hypotension OR shock OR ileus OR megacolon |
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|} |
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===Children=== |
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*Asymptomatic carriage is common in infants (37% at 1 month, decreasing to adult levels of 3-5% by 3 years) [[CiteRef::pediatrics2012cl]] |
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**Thought to be related to a lack of the binding target of ''C. difficile'' toxin |
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*Clinical disease is rare before 12 to 24 months of age |
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== Diagnosis == |
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* Usually done with either nucleic acid testing for the toxin gene, or with an EIA test for GDH and toxin A/B enzyme |
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{| class="wikitable" |
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!Test |
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!Sensitivity |
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!Specificity |
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|- |
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|GDH immunoassay |
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|94-96% |
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|92-95% |
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|- |
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|Toxin A/B enzyme immunoassay |
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|58-83% |
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|99% |
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|- |
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|Parallel GDH and toxin A/B immunoassay |
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|58-82% |
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|99.5% |
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|- |
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|Toxin B PCR |
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|91-96% |
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|96-98% |
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|} |
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==Management== |
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{| class="wikitable" |
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!Severity |
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!First-line[[CiteRef::loo2018as]] |
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!Alternatives |
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|- |
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! colspan="3" |Initial episode |
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|- |
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|Mild to moderate |
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|[[Vancomycin]] 125 mg po QID for 10-14 days |
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|[[Fidaxomicin]] 200 mg po BID for 10 days<br />[[Metronidazole]] 500 mg po TID for 10-14 days |
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|- |
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|Severe, uncomplicated |
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|[[Vancomycin]] 125 mg po QID for 10-14 days<br />[[Fidaxomicin]] 200 mg po BID for 10 days |
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| |
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|- |
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|Severe, complicated |
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|[[Vancomycin]] 125-500 mg po QID for 10-14 days plus [[metronidazole]] 500 mg IV q8h |
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|[[Fidaxomicin]] 200 mg po BID for 10 days plus [[metronidazole]] 500 mg IV q8h<br />Consider rectal vancomycin if ileus |
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|- |
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! colspan="3" |Recurrent episode |
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|- |
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|First recurrence, mild to moderate |
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|[[Vancomycin]] 125 mg po QID for 14 days |
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|[[Fidaxomicin]] 200 mg po BID for 10 days |
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|- |
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|First recurrence, severe, uncomplicated |
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|[[Vancomycin]] 125 mg po QID for 14 days<br />[[Fidaxomicin]] 200 mg po BID for 10 days |
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| |
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|- |
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|Second or subsequent recurrence |
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|[[Vancomycin]] as prolonged tapered or pulsed regimen |
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|Consider fecal microbiota tranplantation after vancomycin |
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|} |
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*For '''rectal vancomycin''', add 500 mg to 100 mL normal saline and give as retention enema every 6 hours |
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*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 |
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=== High Dose Vancomycin === |
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* No clear data supporting high-dose [[vancomycin]], even in severe CDAD[[CiteRef::bader2020re]] |
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=== Tapered-Pulsed Fidaxomicin === |
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* Case series suggest it may be helpful, though recurrence rate still up to 40%[[CiteRef::skinner2021a]] |
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* [[Fidaxomicin]] 200 mg once daily for 7 days followed by 200 mg [[fidaxomicin]] every other day for the remaining 13 doses |
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==Prevention== |
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=== Probiotics === |
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* Insufficient evidence to recommend for or against |
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=== Primary Prophylaxis === |
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*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]] |
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**Included patients with age≥70 years or who were hospitalized in the past 90 days |
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=== Secondary Prophylaxis === |
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* Oral [[vancomycin]] is occasionally used as secondary prophylaxis after a recent (within 3 to 12 months) episode of CDAD |
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* Per the IDSA guidelines, there is insufficient evidence to recommend for or against |
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==Further Reading== |
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*[https://www.ammi.ca/Content/AMMI%20Canada%20treatment%20practice%20guidelines%20for%20Clostridium%20difficile%20infection%2Epdf AMMI treatment practice guidelines for Clostridium difficile infection 2018] |
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*Clostridioides difficile: diagnosis and treatments. ''BMJ''. 2019;366:l4609. doi: [https://doi.org/10.1136/bmj.l46091 10.1136/bmj.l46091] |
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{{DISPLAYTITLE:''Clostridioides difficile''}} |
{{DISPLAYTITLE:''Clostridioides difficile''}} |
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Latest revision as of 17:28, 19 September 2024
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
- 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 used1
- 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
| 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
Diagnosis
- Usually done with either nucleic acid testing for the toxin gene, or with an EIA test for GDH and toxin A/B enzyme
| 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
| 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
High Dose Vancomycin
- No clear data supporting high-dose vancomycin, even in severe CDAD4
Tapered-Pulsed Fidaxomicin
- Case series suggest it may be helpful, though recurrence rate still up to 40%5
- 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 patients6
- 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
- AMMI treatment practice guidelines for Clostridium difficile infection 2018
- Clostridioides difficile: diagnosis and treatments. BMJ. 2019;366:l4609. doi: 10.1136/bmj.l46091
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.
- ^ 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.
