Clostridium difficile Infection (CDI)

Guidelines referenced:

1. 2017 IDSA Clostridium difficile Clinical Practice Guidelines
2. 2018 AMMI Clostridium difficile Clinical Practice Guidelines

Summary

• test only with reasonably high pretest probability of CDI causing active diarrhea (?reasons for altered gut microbiome)
• start with low dose vancomycin for 10 to 14 days
• if severe, (1) quadruple dose of vanco (2) add IV Flagyl (3) consider adding vanco enema (4) might need to call surgery for a megacolon
• if recurrent, generally a long taper of vanco is appropriate
• call ID for help 

Testing for CDI

Indications for Testing

• submit stool samples if NOT on laxatives, and with unexplained and new onset >= unformed stools in 24 hr
• do not repeat testing within 7 days during the same episode of diarrhea or if asymptomatic

Testing Methods/Algorithm

• testing in Ontario is via a combination of glutamate dehydrogenase (GDH) screening + LAMP confirmation (DNA amplification of toxin genes) https://www.publichealthontario.ca/en/laboratory-services/test-information-index/clostridium-difficile

Severity of CDI

There is no accepted consensus for defining these. The IDSA defines CDI infection as one of three severities.

• non-severe
• severe (AKI, leukocytosis ≥ 15)
• fulminant (toxic megacolon, ileus, hypotension, shock)

## Treatment of CDI

Initial Episode

• If non-severe or severe, first-line is vancomycin 125 mg po QID, or fidaxomicin 200mg BID. Duration is 10 days
• Only use oral metronidazole as first-line therapy for non-severe C diff where access to other drugs is limited
• If fulminant, needs aggressive therapy:
  • Vancomycin 500 mg PO/NG QID x 10 days
  • Can also consider adding vancomycin 100 mg PR (retention enema) q6h
  • Metronidazole 500 mg IV q8h, especially with ileus. Should be used with vanco
  • Consider surgical consult

First Recurrence/Relapse

• If metronidazole was used for the first episode, then use vancomycin as above, OR
• If the standard vanco or metronidazole course was used initially, then use a prolonged tapered and pulsed vanco regimen, OR
  • vanco 125 mg QID for 10-14 days, then
  • vanco 125 mg BID for 7 days, then
  • vanco 125 mg OD for 7 days, then
  • vanco 125 mg q2-3 days for 2-8 weeks
  • This is in the IDSA guidelines but not the Canadian guidelines.
• OR, if vancomycin was initially used, then use fixadomycin as above (superior treatment response)

Second or Subsequent Recurrences

• Vancomycin as a prolonged tapered and/or pulsed regimen (e.g., 125 mg po QID for 14 days; 125 mg po TID for 7 days; 125 mg po BID for 7 days; 125 mg po once daily for 7 days, and then every 2 or 3 days for 2–8 weeks)
• Consider fecal microbiota transplantation for recurrence following a vancomycin taper

Prophylaxis Against CDI

• there is limited evidence to support use of low-dose vancomycin during systemic antibiotic therapy for secondary ppx of CDI (https://www.jwatch.org/na49075/2019/05/14/vancomycin-prophylaxis-prevent-recurrent-c-diff-not-so). It may be associated with lower rates of recurrence with just one prior C diff infection.

Other Notes

• generally PO vanco has limited systemic bioavailability but if you are using high doses then it might be OK to check serum levels especially with renal failure, compromised gut, long duration. Generally serum levels are not helpful and should not be ordered.
• IV Flagyl will reach the gut in an ileus, whereas oral vanco will not
• oral vancomycin is superior to metronidazole in placebo controlled RCTs (cure rate 97% vs 84%)
• fidaxomicin is superior to vancomycin for recurrence rates, death at 40 days, or persistent diarrhea (but very expensive and not used much)
• can extend duration from 10 to 14 days if still symptomatic but improving
• long-term metronidazole has risk of neurotoxicity