Photomicrograph courtesy of SL Gorbach

C. difficile Screening and Identification Fact or Fiction

Lisa E Davidson, MDTufts Medical Center

Boston, MA

Disclosures

None

Objectives: Fact or Fiction Clinical Presentation

You can only get C difficile in the hospitalColonization makes you more likely to develop active diseaseDiarrhea is required for the diagnosis of C difficile infectionNurses are very good at diagnosing C difficile by smellOnly older antibiotics are associated with C difficile infection

Identification and testingI only need to send one loose, stool specimen to the micro lab

Treatment:Metronidazole is recommended initial treatment of mild to Metronidazole is recommended initial treatment of mild to

moderate CDImoderate CDIPrompt initial treatment prevents recurrenceAlternative therapies such as probiotics are well proven to

treat/prevent C difficile infection

Fact or Fiction: You can only get Fact or Fiction: You can only get CC difficiledifficile in the hospital in the hospital

Fiction:Fiction: Most commonly acquired in the hospital Most commonly acquired in the hospital Risk factors include antibiotic exposure, immune Risk factors include antibiotic exposure, immune

function age, exposure to PPIsfunction age, exposure to PPIs Becoming increasingly common in outpatientBecoming increasingly common in outpatient

UK: incidence rose from less than 1 case per UK: incidence rose from less than 1 case per 100,000 persons to 20 per 100,000 between 1994 100,000 persons to 20 per 100,000 between 1994 and 2004 (1)and 2004 (1)

Reports in peripartum women and healthy individuals Reports in peripartum women and healthy individuals with no known risk factors (2)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):2989-952) MMWR Morb Mortal Wkly Rep. 2005;54(47):1201-5.

Fact or Fiction: Colonization makes you Fact or Fiction: Colonization makes you more likely to develop active diseasemore 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 asymptomaticColonization ≠ toxin production

New acquisition of C. difficile is more likely to lead to CDAD (4)

1) N Engl J Med. 2000;342(6):390-72) N Engl J Med. 1989;320(4):204-10.3) Clin Infect Dis. 2007;45(8):992-84) N Engl J Med. 1989;320:204-210

Fact or Fiction: Diarrhea is Fact or Fiction: Diarrhea is required for the diagnosis of required for the diagnosis of C C difficiledifficile infection infection

Fact: SHEA/IDSA definition(1)presence of diarrhea (3 or more unformed

stools) in 24 hrs(2) a stool test result positive for the presence of toxigenic C.

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

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

80%!!

Fact or Fiction: Only older antibiotics Fact or Fiction: Only older antibiotics are associated with are associated with C difficile C difficile infectioninfection

Fiction: ALL antibiotics have been associated with CDI

High risk antimicrobialsFluoroquinolones, especially gati, moxi, levo

fluoroquinolone resistance of the NAP1/BI/027 strain is associated with increased virulence

2nd & 3rd generation cephalosporinsClindamycinAmpicillin, amoxicillin/clav, Pip/tazo, Ticar/clav

Intermediate risk antimicrobialsTMP/SMXMacrolides

Low risk antimicrobialsAminoglycosidesVancomycinMetronidazole

Fact or fiction: I only need to Fact or fiction: I only need to send one, loose stool specimen send one, loose stool specimen to the micro labto 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

DIAGNOSTIC TESTS FOR CLOSTRIDIUM DIFFICILE

Slide courtesy of SL Gorbach

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.

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/bStep 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).

Fact or fiction: Metronidazole is Fact or fiction: Metronidazole is recommended initial treatment of recommended initial treatment of mild to moderate CDImild to moderate CDI

FACT: current IDSA guidelines recommend metronidazole for initial therapy of mild-moderate CDI

ICHE May 2010, vol. 31, no. 5Clin Infect Dis. 2007;45(3):302-7.

Initial treatment: factors to considerInitial 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?

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

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

Fact or Fiction: Alternative therapies Fact or Fiction: Alternative therapies such as probiotics are well proven to such as probiotics are well proven to treat/preventtreat/preventC difficile C difficile infectioninfection

Fiction: Probiotics have NOT been proven effective by rigorous clinical trials to prevent or treat CDI(1)Many small trials, not many placebo

controlledSlightly better results on prevention of

recurrence than treatmentLactobacillus GG 1 capsule po twice

daily for 14 daysSaccharyomyces boulardii 500 mg

capsule twice daily for 4 weeks1) Pillai A, Nelson R. Probiotics for treatment of Clostridium difficile-associated colitis in adults.Cochrane Database Syst Rev. 2008;