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Photomicrograph courtesy of SL Gorbach

Photomicrograph courtesy of SL Gorbach. C. difficile Screening and Identification Fact or Fiction . Lisa E Davidson, MD Tufts Medical Center Boston, MA. Disclosures . None. Objectives: Fact or Fiction. Clinical Presentation You can only get C difficile in the hospital

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Photomicrograph courtesy of SL Gorbach

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  1. Photomicrograph courtesy of SL Gorbach C. difficile Screening and Identification Fact or Fiction Lisa E Davidson, MDTuftsMedical CenterBoston, MA

  2. Disclosures • None

  3. Objectives: Fact or Fiction • Clinical Presentation • You can only get C difficile in the hospital • Colonization makes you more likely to develop active disease • Diarrhea is required for the diagnosis of C difficile infection • Nurses are very good at diagnosing C difficile by smell • Only older antibiotics are associated with C difficile infection • Identification and testing • I only need to send one loose, stool specimen to the micro lab • Treatment: • Metronidazole is recommended initial treatment of mild to moderate CDI • Prompt initial treatment prevents recurrence • Alternative therapies such as probiotics are well proven to treat/prevent C difficile infection

  4. Fact or Fiction: You can only get Cdifficile in the hospital Fiction: • Most commonly acquired in the hospital • Risk factors include antibiotic exposure, immune function age, exposure to PPIs • Becoming increasingly common in outpatient • UK: incidence rose from less than 1 case per 100,000 persons to 20 per 100,000 between 1994 and 2004 (1) • Reports in peripartum women and healthy individuals with no known risk factors (2) • May-June 2005: 10 peripartum and 23 community acquired cases in 4 states -48% in children (11/33). • 8/33 had no exposure to antibiotics in 3 months prior to illness • 3/33 had minimal exposure (2 were given one dose of Clindamycin for elimination of Group B Strep carriage peripartum. 1) JAMA. 2005;294(23):2989-95 2) MMWR Morb Mortal Wkly Rep. 2005;54(47):1201-5.

  5. Fact or Fiction: Colonization makes you more likely to develop active disease Fiction: • About 20% of non colonized patient become colonized during their hospitalization (1-3) • C. difficile carriage occurs in 20 to 50 percent of adults in long term care facilities (1-3) • Patients colonized with C. difficile are more likely to be asymptomatic • Colonization ≠ toxin production • New acquisition of C. difficile is more likely to lead to CDAD (4) 1) N Engl J Med. 2000;342(6):390-7 2) N Engl J Med. 1989;320(4):204-10. 3) Clin Infect Dis. 2007;45(8):992-8 4) N Engl J Med. 1989;320:204-210

  6. Fact or Fiction: Diarrhea is required for the diagnosis of C difficile infection Fact: SHEA/IDSA definition • presence of diarrhea (3 or more unformed stools) in 24 hrs • a stool test result positive for the presence of toxigenicC. difficile or its toxins or colonoscopic or histopathologic findings demonstrating pseudomembranous colitis. • Watery diarrhea up to 10 or 15 times daily • lower abdominal pain and cramping • Fever • Leukocytosis • CDAD is reported to routinely be associated with a WBC on average of 15K • Higher with colitis ICHE Vol. 31, No. 5 (May 2010), pp. 431-455

  7. Fact or Fiction: Nurses are very good at diagnosing C difficile by smell

  8. 80%!!

  9. Fact or Fiction: Only older antibiotics are associated with C difficile infection Fiction: ALL antibiotics have been associated with CDI High risk antimicrobials Fluoroquinolones, especially gati, moxi, levo • fluoroquinolone resistance of the NAP1/BI/027 strain is associated with increased virulence 2nd & 3rd generation cephalosporins Clindamycin Ampicillin, amoxicillin/clav, Pip/tazo, Ticar/clav Intermediate risk antimicrobials TMP/SMX Macrolides Low risk antimicrobials Aminoglycosides Vancomycin Metronidazole

  10. Fact or fiction: I only need to send one, loose stool specimen to the micro lab • FACT: Testing for C. difficile or its toxins should be performed only on diarrheal (unformed) stool, unless ileus due to C. difficile is suspected • Because of the low increase in yield and the possibility of false-positive results, routine testing of multiple stool specimens is not supported as a cost-effective diagnostic practice (1) 1) J Clin Microbiol. 2008;46(11):3686-9

  11. Slide courtesy of SL Gorbach DIAGNOSTIC TESTS FOR CLOSTRIDIUM DIFFICILE Mylonakis et al., 2001 MORE RECENT NUMBERS for ELISAs C. Diff ToxA/B II (TechLab, VA) Se/Sp: 88.3%/100% ProSpecT C. Diff tox A/B microplate (Remel) Se/Sp: 93.3%/100% Vs. “gold standard” = cytotoxin assay for B combined with tcdA and tcdB PCR Eur. J. Clin. Microbiol. Infect. Dis 2007;26:115-119.

  12. Enzyme immunoassay (EIA) allows direct detection of C difficile toxins in stool • good specificity (up to 99%), variable sensitivity (60 to 95%) • relatively high false negative rate because need a higher level of toxin present • Newer ELISA using C. difficile common antigen (GDH ) Step one: ELISA GDH antigen and toxin a/b Step two: (ag+ and toxin- ) amplification test for toxin loci • Real-time PCR assays for toxin B (Cepheid Gene Xpert), BD-GeneOhn C diff assay, and IVD RT-PCR (Pro-gastro, Prodesse).

  13. Fact or fiction: Metronidazole is recommended initial treatment of mild to moderate CDI • FACT: current IDSA guidelines recommend metronidazole for initial therapy of mild-moderate CDI ICHE May 2010, vol. 31, no. 5 Clin Infect Dis. 2007;45(3):302-7.

  14. Initial treatment: factors to consider • Age • Peak white blood cell count (leukocytosis) • Severity of illness – evidence of organ dysfunction or sepsis • Is the GI tract working?

  15. ICHE Vol. 31, No. 5 (May 2010), pp. 431-455

  16. Fact or fiction: Prompt initial treatment prevents recurrence FICTION: Relapse occurs in 6-30% of cases • Not related to severity of diarrhea, inciting antibiotic or length of diarrhea • Strain is usually the same, with identical antibiotic sensitivities as original isolate • In hospital, relapse can be confused with re-infection • Retreatment can use the original drug for a 14 day course • Two thirds of patients relapse again within 4 weeks of initial treatment • Risk of recurrence increases with each subsequent recurrence

  17. Fact or Fiction: Alternative therapies such as probiotics are well proven to treat/preventC difficile infection • Fiction: Probiotics have NOT been proven effective by rigorous clinical trials to prevent or treat CDI(1) • Many small trials, not many placebo controlled • Slightly better results on prevention of recurrence than treatment • Lactobacillus GG 1 capsule po twice daily for 14 days • Saccharyomycesboulardii 500 mg capsule twice daily for 4 weeks 1) Pillai A, Nelson R. Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database Syst Rev. 2008;

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