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
 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
Fact or Fiction: You can only get C difficile 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.
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
Fact or Fiction: Diarrhea is required for the
diagnosis of C difficile 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 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
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
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.
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).
Fact or fiction: Metronidazole is recommended initial
treatment of mild to moderate CDI

FACT: current IDSA guidelines recommend
metronidazole for initial therapy of mildmoderate CDI
ICHE May 2010, vol. 31, no. 5
Clin Infect Dis. 2007;45(3):302-7.
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?

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 such as probiotics
are well proven to treat/prevent
C 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
 Saccharyomyces boulardii 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;