antibiotic associated diarrhea clostridium difficile infection

1. Dr Santosh M Narayankar
Clostridium difficile Infection

2. Antibiotic Associated Diarrhea(AAD)
 Common side effect of antibiotic
 Multiple mechanisms
 2-25% of antibiotic treatments
 Results from colonic microflora alteration

3. AAD-Mechanisms Of Diarrhea
 Motilin Receptor Agonist- Erythromycin
 Stimulate Bowel Peristalsis- Clvulanate
 Intestinal Flora Alteration-
Decreased Carb Metabolism
Altered Bile Acid Metabolism
 Overgrowth of pathogenic organisms

4. Major Infectious Agents
Causative agent unknown in most of the cases
 Candida overgrowth- controversial
 Clostridium Perfringes- Food poisoning, Necrotizing
enterocolitis (15%)
 Staph Aureus-Food poisioning,diarrhea (7%)
 Klebsiella Oxytoca -Antibiotic AssociatedHemorrhagic
Colitis (AAHC)
 Clostridium Difficile - 30% AAD in hospital

5. Differences between AAD- CDI And From
Other Causes

6. Clostridium Difficile
Infection(CDI)

7. Clostridium Difficile
 Gram Positive
 Anaerobe
 Spore forming
 Toxin producing-A & B
 Feco -oral route
 Non invasive
 Asymptomatic to severe
C. difficile 30% of AAD cases but is an important pathogen to identify
because it often requires specific antimicrobial therapy and can lead to
life-threatening complications

8. Definitions

9. CDI-Epidemiology
 Healthy adults
 In patients
 Healthy infants
0 to 3%
10-21%
25-80%
C. difficile associated diarrhoea (CDAD) in India
reveal a prevalence rate ranging from 7.1-26.6% with
fewer cases of fulminant infections

10. High risk for CDI
 Antimicrobial agent
 Older age >65 years
 In patient care
 Increased co morbidities
 PPI
 Chemotherapy
 HIV infection
 IBD
 Manipulation of GIT –
tube feeding,surgery
 Duration of
hospitalisation

11. Antimicrobial Agents-Predispose to
Clostridium difficile Infection
Any antibiotic, any dose, for any duration

12. Pathogenesis CDI

13. Clostridium Difficile Pathogenecity Locus

14. Structure and function of Clostridium
difficile toxins

15. Clinical features -CDI
 Asymptomatic
Clinical Clinical criteria
Mild Diarrhea (<6 BM/day), No fever
No peritoneal signs,
No evidence of sepsis
Moderate Diarrhea (6-12 BM/day), fever ,frankly visible stable lower GI
bleeding
Severe Diarrhea(>12 BM/day), fever ,hemodynamic instability, marked
and continuous abdominal pain, ileus, absence of bowel sounds,
evidence of sepsis, or intensive care unit level of care is required

16. Severity

17. Diagnosis
 Only stools from patients with diarrhea should be tested
 NAAT for C. difficile toxin genes such as PCR are
superior to toxins A + B EIA
 Glutamate dehydrogenase (GDH) screening tests can
be used in two- or three-step screening algorithms with
subsequent toxin A and B EIA testing, but the sensitivity
of such strategies is lower than NAATs
 Repeat testing should be discouraged
 Testing for cure should not be done

18. Stool Tests for the Diagnosis of
Clostridium difficile Infection

19. Colonoscopic Images-CDI
 Raised adherent yellow
plaques that vary in size
from 2 to 5 mm are visible
on the colonic mucosa.
 In some areas, coalescing
pseudo membranes are
evident.
 There is some erythema
of the colonic mucosa
between the
pseudomembranes,but
the epithelium is intact

20. Pseudo membranous Colitis
Histopathology
 Focal ulceration of
the colonic mucosa
is evident with
exudation of a
pseudomembrane
made up of
inflammatory cells,
fibrin, and necrotic
debris
 The adjoining
mucosa is intact
Volcano Or Summit Lesion

21. Accordion Sign On CT
Produced by a series of broad oedematous colonic haustral folds

22. Toxic mega colon X-ray & CT

23. Treatment-General approach

24. Treatment-Mild To Moderate
 Strong suspicion for CDI- Empiric therapy
 Antimicrobial agent(s) should be discontinued, if
possible
 Should be treated with metronidazole 500 mg orally
three times per day for 10 days.
 Failure to respond to metronidazole within 5 – 7 days
should prompt consideration of a change in therapy to
vancomycin at standard dosing.

25. Treatment-Mild to Moderate
 Who are intolerant / allergic to metronidazole and for
pregnant / breastfeeding women, vancomycin should
be used at standard dosing.
 Hartman’s pouch, ileostomy, or colon diversion,
vancomycin therapy delivered via enema.
 Anti-peristaltic agents to control diarrhea from
confirmed or suspected CDI should be avoided

26. Severe CDI
 Supportive care should be delivered
 CT scanning of the abdomen and pelvis
 No Abd Distension -Vancomycin delivered orally (125 mg
four times per day) plus intravenous metronidazole (500
mg three times a day)
 Abdominal Distension -Vancomycin delivered orally (500
mg four times per day) and per rectum (500 mg in a
volume of 100 ml four times a day) plus intravenous
metronidazole (500 mg three times a day).

27. Surgery –When?
 Hypotension requiring vasopressor therapy
 Clinical signs of sepsis and organ dysfunction (renal
and pulmonary)
 Mental status changes
 White blood cell count ≥ 50,000 cells / μ l
 Lactate ≥ 5 mmol / l
 Or failure to improve on medical therapy after 5 days.

28. Treatment-IDSA guideline update 2018

29. Management of recurrence

30.  IBD pts hospitalized with a disease flare should
 Undergo testing for CDI
 Simultaneous initiation of empiric therapy directed
against CDI and treatment of an IBD flare
 Escalation of immunosuppression medications should
be avoided
 Surgically created pouch after colectomy may develop
CDI and should be tested if they have symptoms.
Management of patients with CDI and co-
morbid conditions

31. Management of patients with CDI and co-
morbid conditions
 Underlying immunosuppression - should tested
 Any diarrheal illness in women who are pregnant or
periparturient should -Prompt testing

32. Fecal Microbiota Transplantation
 Cure rates greater than 85% and many greater than
90%.
 First RCT was performed by van Nood and
colleagues with FMT for rCDI through the
nasoduodenal route. Given that 81% of patients with
rCDI had resolution of C. difficile associated disease
(CDAD) after 1 infusion compared with 31% of
patients receiving vancomycin only (P<.001),the study
was terminated early following interim analysis.
 There have been 2 randomized controlled trials
showing efficacy of FMT via colonoscopy

33. Infection Control and Prevention
 Antibiotic stewardship
 Contact precautions
 Isolation
 Hand hygiene and barrier precautions,
 Single-use disposable equipment should be used
 Disinfection of environmental surfaces
 Insufficient evidence that probiotics prevent C. difficile
infection

34. C Difficile Vaccine
 Which contains inactivated toxoid A and B.
 Immunogenic and in a small case series,
vaccination was associated with resolution of
recurrent C. difficile diarrhea
 If effective, these therapeutic approaches also
may be useful to prevent C. difficile-associated
diarrhea in high-risk persons, such as older adults
and infirm patients receiving antibiotic therapy in
the hospital

35. Bezlotoxumab, a monoclonal antibody against TcdB
recently approved by the US Food and Drug
Administration (FDA), reduces the rate of CDI
recurrence in adults.
 However, the protective effect of this passive
immunization strategy is short-lived.

36. Thank You