Tres Difficile

Stephen M. Brecher PhD

Director of Microbiology
VA Boston Health Care System
West Roxbury, Massachusetts
 The opinions expressed in this
presentation are those of the
presenter and do not necessarily
represent the views of the Veterans
Affairs Health-Care System
 The Dominant Species

The human body has

13
10 human cells and
a minimum of 10 14

bacterial cells
 Overview
• Case reports • Changing
• Historical epidemiology
perspective • Disease
• Organism & key • Diagnosis
properties • Treatment
• Infection control
 Case Study 1
• 60 yo male admitted to hospital for community
acquired pneumonia, treated with levofloxacin
and discharged
• 7 days later, seen at another hospital because of
12-15 pound weight gain over last few days (“my
abdomen has never been so big”) and
hypertension (213/106)
– Afebrile, WBC of 8.5, albumin 3.1, creatinine 0.9, no
diarrhea noted
– Admitted, treated for hypertension and ciprofloxacin
given to complete treatment for CAP; discharged 3
days later
 Case Study 1 (cont’d)
Day 1 Presents to ER 3 days after discharge
• Fever (101), diarrhea, generally feeling ill, no
abdominal pain
• WBC 27.8K, albumin 2.9, creatinine 1.2
• Admitted with C. difficile colitis listed as a
possible dx, but not treated (except for
levofloxacin)
Day 2 10 stools/day, altered mental status
• C. difficile EIA positive; put on metronidazole
500 mg TID
 Case Study 1 (cont’d)
Day 3 Transferred to SICU, anuric,
abdominal pain, distension,
developed cardiac complications,
ventilated, renal failure. Poor
prognosis and colectomy ruled out
following surgical consult
• Oral and rectal vancomycin added
• WBC > 30K, albumin 2.3, creatinine 3.1

Day 4 WBC 59.6K, toxic megacolon

Day 5 WBC 88K, made DNI/DNR, died
 Historical Perspective
• In the 1960s it was noted that patients on
antibiotics developed diarrhea1
– “staphylococcal colitis”
• Originally thought to be caused by S. aureus and treated with
oral bacitracin
• Stool cultures routinely ordered for S. aureus
• Early 1970s, a new explanation
– “clindamycin colitis”
• Severe diarrhea, pseudomembranous colitis, and occasional
deaths documented in patients on clindamycin

1. Gorbach SL. NEJM. 1999;341:1689-1691.

 “Antibiotic Associated
Pseudomembranous Colitis Due to
Toxin-Producing Bacteria”
• Bartlett and co-workers1 demonstrated
cytotoxicity in tissue culture and enterocolitis in
hamsters from stool isolates from patients with
pseudomembranous colitis
– Isolate was C. difficile
• Bacillus difficilis (now confirmed as C. difficile)
was cultured from healthy neonates (with
difficulty, hence the name) in 19352

1. Bartlett JG, et al. NEJM. 1978;298: 531-534.

2. Hall JC and O’Toole E. Am J Dis Child. 1935;49:390-402.
 Quiz Time
Q. Why did it take so long to associate the
organism C. difficile with the disease?
A. Organism was (is) found in healthy
infants

Q. Why do antibiotics sometimes cause

diarrhea (unrelated to C. difficile)?
A. Disrupt the intestinal flora which plays a
major role in digestion of food
 Clostridium difficile
• Gram-positive, anaerobic, spore-forming
bacillus
• Vegetative cells die quickly in an aerobic
environment
• Spores are a survival form and live for a
very long time in the environment
• Grows on selective media in 2 days and
smells like horse manure (p-cresol)
 Importance of Spores
• Resistant to heat, drying, pressure, and
many disinfectants
• Resistant to all antibiotics because
antibiotics only kill or inhibit actively
growing bacteria
• Spores survive well in hospital
environment
• Spores are not a reproductive form, they
represent a survival strategy
 Source of Infections
• Spores in hospital, nursing home, or long-term
care environment associated with ill patients
– Large numbers of spores on beds, bed-rails, chairs,
curtains, medical instruments, ceiling, etc.
• Asymptomatic carriers in those same
environments
– Low risk compared to patients with active disease
• False negative lab tests (low sensitivity)
• Unknown in community based infections, but
food has been implicated1
1. Jhung MA, et al. Emerg Infect Dis. 2008;14:1039-1045.
 Risk Factors for Infection
• Hospitalization or long-term care facility
• Antibiotics (some more than others)
• Increasing age (>65, >>80)
• Co-morbidity
• Surgery
• ? Proton-pump inhibitors
• Community-associated cases
– Peri-partum
– Close contact of CDI (C. difficile infection) case
– Food
 Case Study 2
• 31 yo pregnant female (14 weeks, twins) seen at
a local ER with history of
– 3 weeks intermittent diarrhea
– 3 days cramping and watery diarrhea
– Stool + for C. difficile toxin
– Received T/S for UTI 3 months prior to ER visit
– Admitted, treated with metronidazole and discharged
– Readmitted next day with severe colitis
– Treated in hospital for 18 days with metronidazole,
oral vancomycin and cholestyramine, discharged
 Case Study 2 (cont’d)
• Readmitted 4 days later
– Diarrhea and hypotension
– Spontaneously aborted her fetuses
– Subtotal colectomy, aggressive therapy
– Died on 3rd day
– Post-mortem showed toxic megacolon with
evidence of pseudomembranous colitis

MMWR 54:(47);1201-1205.
 What Can We Learn From
Case 2?
• We know nearly nothing about community
based CDI
• Testing for C. difficile is now both an in-
patient and out-patient test
• Risk factors other than colonic imbalance
mediated by antibiotics must be
considered
 Role of Antibiotics
• All antibiotics (including metronidazole and
vancomycin) are associated with CDI
• High-risk group
– Clindamycin
– Cephalosporins/penicillins/beta-lactams
– Fluoroquinolones
• Alteration of normal colonic flora thought to favor
growth of C. difficile
– Antibiotics do not know they are suppose to kill/inhibit
only the “bad guys”
 Pathogenesis
Historical Perspective
• Most CDI were mild
– Diarrhea was main symptom
– Pseudomembranous colitis and toxic
megacolon were rare
– Discontinuing antibiotics worked in many
cases
– High response rate to metronidazole and
vancomycin
 Incidence of CDI
• United States
– CDI is not a reportable disease so exact
number of cases and deaths remain unknown
– Based on discharge diagnoses, CDI cases
have tripled over last 5 years
• United Kingdom
– Deaths in UK ~ 9,000/year

CDI = C. difficile infection.

 Pathogenesis
• Toxigenic strains produce 2 large protein
exotoxins that are associated with virulence
– Toxins A and B
– Mutants strains that do not make toxins A and B are
not virulent
– Some strains make a third toxin known as Binary
Toxin
• By itself, not pathogenic
• May act synergistically with toxins A and B in severe colitis
• More common in animal strains
 Pathogenesis of CDI

Antimicrobial Asymptomatic
C. difficile
colonization

C. difficile exposure
C. difficile
Hospitalization infection

From Johnson S, Gerding DN. Clin Infect Dis. 1998;26:1027-1036; with permission.
 Pathogenesis
Changing Epidemiology
• Increasing morbidity and mortality noted
beginning in 2000
• Outbreaks in US & Canada (>200 deaths)
• Was this due to poor infection control,
emergence of antibiotic resistance, or
something else?
• A new, hypervirulent strain was detected
 Epidemic Strain
• Strain typed BI/NAP1/0271,2
• Is highly resistant to fluoroquinolones2,4
• Binary toxin genes are present
• Produces large quantities of toxins A and B1,3
• Has a tcdC gene deletion1

1. Warny M, et al. Lancet. 2005;366:1079-1084.

2. Hubert B, et al. Clin Infect Dis. 2007;44:238-244. Adapted from McDonald LC, et al. N Engl J Med. 2005;353:2433-2441; with
3. CDC Fact Sheet. July 2005. permission.
4. McDonald LC, et al. N Engl J Med. 2005;353:2433-2441.
 In Vitro Production of Toxins
in Epidemic Strain

From Warny M, et al.

Lancet. 2005;366:1079-
1084, with permission.
 Not So Fast
• 2 recent papers questioned whether this
strain is more virulent
– NAP-1 strain was detected around 25% of
time in their hospital (BID in Boston) but was
not associated with increased severity of
disease (non-epidemic setting)1
– 18 and 39 bp deletion containing strains were
not associated with increased severity of CDI
at the Mayo Clinic2
• Age >65 and prior NH stay implicated
1. Cloud, J. et al. 2009. Cl Gastro and Hept. 7:868-873
2. Verdoorn, B. P. et al. Diag Micro and ID. 10.1016/j.diagmicrobio.2009.0815
 Should You Treat the Patient
or Treat the Strain?
• Routine diagnostics laboratory tests do not
provide strain type
• Routine tests not always reliable
• Always treat the patient based symptoms,
history, risk factors and markers of severe
disease
 Symptoms of CDI
• Asymptomatic colonization
• Diarrhea
mild  moderate  severe
• Abdominal pain and distension
• Fever
• Pseudomembranous colitis
• Toxic megacolon
• Perforated colon  sepsis  death
 Markers of Severe Disease
• Leukocytosis
– Prominent feature of severe disease
– Rapidly elevating WBC
– Up to >100 K
• >10 BM/day
• Albumin < 2.5
• Creatinine 2x baseline
• Hypertension
• Pseudomembranous colitis
• Toxic megacolon
• Severe distension and abdominal pain
Laboratory Diagnosis of
C. difficile Infection (CDI)
 Which Test Should I Use?
• Considerations
– Accuracy
– Time to detection
– Prevalence in your population
• Screening tests followed by confirmatory tests
• In a low prevalence population, a screening test with a high
sensitivity is useful (no/few false negatives)
– Cost
– Ease of use
• At this time, there is no perfect test for the
diagnosis of CDI
 What Should I do First?
Make some rules
• Rule 1: Accept only liquid stools or soft
stools
– Why? Any Exceptions?
• Rule 2: Limit repeat testing once a patient
is positive
– Why? Any exceptions
 The Specimen
• Fresh is best (test within 2 hours)
• Liquid or loose, not solid
• If unable to test within 2 hours, refrigerate
at 4°C for up to 3 days
• Freeze at -70°C (not -20°C) if testing
will be delayed
• Specimen quality will influence test results

In: Manual Clin Micro. 9th ed. 2007;p. 897.

 Laboratory Diagnosis of CDI
Enzyme Immunoassay (EIA)
Glutamate
Dehydrogenase (GDH)
Cell Culture
Neutralization
Laboratory Assay (CCNA)
Diagnosis
Toxigenic Culture
(Culture and CCNA)
Stool Culture

Molecular Based (PCR Or LAMP)

 Conflicting Results with EIA

Recently Published EIA Papers(1-6)

Parameter Range
Sensitivity 32 – 98.7%
Specificity 92 – 100%
PPV 76.4 – 96%
NPV 88 – 100%

1. Stamper PD, et al. J Clin Microbiol. 2009;47:373-378.

2. Musher DM, et al. J Clin Microbiol. 2007;45:2737-2739.
3. Sloan LM, et al. J Clin Microbiol. 2008;46:1996-2001.
4. Gilligan PH. J Clin Microbiol. 2008;46:1523-1525.
5. Ticehurst JR. J Clin Microbiol. 2006;44:1145-1149.
6. Nice review by Planche T, et al. 2008. www.thelancet.com/infection
 EIA Testing
Advantages Disadvantages
• Rapid • Great variations in
• Inexpensive published sensitivity
• Relatively easy and specificity
• No costly equipment • Technologist error
• Batch or single test • Contamination
formats
 Two-Step Tests1-3
Screening Tests Confirmatory Tests
• Glutamate dehydrogenase • CCNA
(GDH) – Add 1-2 days
– Detects nearly all true • CX followed by CCNA
positives as well as false
positives – Add 3-4 days
– Low PPV • PCR
– High sensitivity – Possibility of false positives
• Very few false negatives due to colonization
– Works best in a low-
prevalence population
• EIA: Is it accurate enough
to use as a screening test?
Confirmatory test?
1. Gilligan PH. J Clin Microbiol. 2008;46:1523-1525.
2. Ticehurst JR. J Clin Microbiol. 2006;44:1145-1149.
3. Planche T, et al. 2008. www.thelancet.com/infection
 Most Recent Studies
• Cdiff Quik Chek Complete (GDH and EIA
on one test card)1
– Both + = +
– Both - = -
– 13.2% discrepant, re-test. Use PCR
• PCR had very high S,S, PPV and NPV2
• PCR resolved low false positive EIA3
1. Quinn, C. D. 2010. J Clin Microbiol. 48: 603-605
2. Novak-Weekley, S. et al. 2010. J. Clin Microbiol.doi:10.1128/JCM.01801-09
3. Brecher, S. et al. 2009. ICAAC Abstract D-1422
 Molecular-Based Assays
• Polymerase Chain Reaction (PCR)
• 3 FDA Approved test kits
• 2 of them are less expensive but more labor
intensive
• 1 is easy enough to do that even I can do it, but is
expensive
• I recently switched from an EIA to the
expensive PCR
– The cost of a misdiagnosed patient is too
great, especially for our Veterans
Treatment
 Treatment of
Mild to Moderate Disease
• Stop antibiotic(s) if medically reasonable
• Metronidazole
– Oral or IV, 500 mg TID for 10-14 days is
standard therapy
– 5–20% failure rate
– 20% relapse rate
– Can use a full 2nd course for failure/relapse
but beyond 2 courses, switch to vancomycin
– Failures not due to metronidazole resistance
Initial Treatment Options for CDI
• Historical response (96%) and relapse rates (20%)
similar between metronidazole and vancomycin1
• More recently, efficacy of metronidazole for severe
disease called into question2-4
• Recent prospective trials report vancomycin to be
superior to metronidazole in severe CDI5-7

1. Aslam S, et al. Lancet Infect Dis. 2005;5:549-557.

2. Fernandez A, et al. J Clin Gastroenterol. 2004;38:414-418.
3. Gerding DN. Clin Infect Dis. 2005;40:1598-1600.
4. Musher DM, et al. Clin Infect Dis. 2005;40:1586-1590.
5. Lahue BJ, Davidson DM. The 17th ECCMID Meeting, March 31 to April 4, 2007; Munich, Germany.
Abstract 1732_215.
6. Zar FA, et al. Clin Infect Dis 2007;45:302-307.
7. Louie T, et al. The 47th Annual ICAAC Meeting, Sept. 17-20, 2007; Chicago, IL. Abstract k-425-a.
Initial Treatment Options for CDI

Metronidazole • May be administered PO or IV

250 mg QID or • Development of resistance rare
500 mg TID • Historical first-line agent
Vancomycin • Effective in enteral (oral or rectal) form only
125 mg QID • Typically reserved for severe disease, those
failing to respond to metronidazole, or
cases in which metronidazole is
contraindicated

IV=intravenously; PO=orally.
Fekety R. Am J Gastroenterol. 1997;92:739-750.
Gerding DN, et al. Infect Control Hosp Epidemiol. 1995;16:459-477.
American Society of Health-System Pharmacists. Am J Health-Syst Pharm. 1998;55:1407-1411.
 Metronidazole vs Vancomycin
• Zar et al1 classified patients as mild or
severe CDI
• In mild disease, vancomycin was slightly
better than metronidazole (98% vs 90%)
– Not statistically significant
• In severe disease, vancomycin was
significantly better than metronidazole
(97% cure vs 76% cure)

1. Zar FA, et al. CID. 2007;45: 302-307.

 Clinical Success by Disease
Severity: Tolevamer Phase III Results
Defining CDI Disease Severity
Mild CDI 3–5 BM/day
WBC ≤15,000/mm3
Mild abdominal pain due to CDI
Moderate CDI 6–9 BM/day
WBC 15,001 to 20,000/mm3
Moderate abdominal pain due to CDI

Severe CDI ≥ 10 BM/day

WBC ≥20,001/mm3;
Severe abdominal pain due to CDI
Any one of the 3 defining characteristics assigns a patient to the more severe category.

Louie T, et al. The 47th Annual ICAAC Meeting, Sept. 17-20, 2007; Chicago, IL. Abstract k-425-a.
Metronidazole vs Vancomycin
vs Tolevamer

• Patients stratified as mild, moderate, or severe

• Original goal of study was to evaluate tolevamer
as a treatment for CDI

Drug Mild Moderate Severe

Tolevamer 59 46 37
Metronidazole 79 76 65
Vancomycin 85 80 85
Louie et al. ICAAC AbstractK-425-9 2007
 C. difficile Infection: Case 3
• 79-year-old woman with multiple medical problems admitted to
hospital for treatment of community-acquired pneumonia
• Responds slowly to levofloxacin 750 mg daily
• After 6 days
– Develops diarrhea (9 loose BMs)
– WBC count: 11,500/mm3
• Day 7–14 loose BMs, WBC count rises to 19,500/mm3
• Stool testing for C. difficile toxins A and B is requested
• Continued antibiotic therapy for pneumonia is deemed necessary

• How would you manage her care?

A. Await stool test results and monitor her progress
B. Empirically start metronidazole PO
C. Empirically start metronidazole IV
D. Empirically start vancomycin PO
 C. difficile Infection: Case 3
• 79-year-old woman with multiple medical problems admitted to
hospital for treatment of community-acquired pneumonia
• Responds slowly to levofloxacin 750 mg daily
• After 6 days
– Develops diarrhea (9 loose BMs)
– WBC count: 11,500/mm3
• Day 7–14 loose BMs, WBC count rises to 19,500/mm3
• Stool testing for C. difficile toxins A&B is requested
• Continued antibiotic therapy for pneumonia is deemed necessary

• How would you manage her care?

A. Await stool test results and monitor her progress
B. Empirically start metronidazole PO
C. Empirically start metronidazole IV
D. Empirically start vancomycin PO
 Treatment of Severe Disease
• Follow definition of severe disease
– >10 BM/day, high WBC, low albumin
• This is a life-threatening infection
• Surgical consultation recommended as
patient may require a colectomy
• Oral vancomycin drug of choice
– Dose varies based on severity
– Can add metronidazole (oral or IV)
 Management of Severe CDI
• Early recognition is critical
– Initiate therapy as soon as diagnosis is suspected
• Manage as for mild CDI plus:
– Oral vancomycin (125 mg QID for 10 to 14 days) as initial
treatment
• If patient is unable to tolerate oral medication, consider
intracolonic vancomycin instillation (by enema)
– 0.5–1 g vancomycin (IV formulation) in 0.1 to 0.5 L of normal
saline via rectal (or Foley) catheter
– Clamp for 60 minutes
– Repeat every 4–12 hours
Gerding DN, et al. Infect Control Hosp Epidemiol. 1995;16:459-477.
Zar FA, et al. Clin Infect Dis. 2007;45:302-307.
Louie T, et al. The 47th Annual ICAAC Meeting, Sept. 17-20, 2007; Chicago, IL. Abstract k-425-a.
Apisarnthanarak A, et al. Clin Infect Dis. 2002;35:690-696.
 Management of Severe,
Complicated CDI
• Potential role of intravenous immunoglobulin G (IVIG)1-6
– Antitoxin A IgG predicts clinical outcome of CDI
– Serum antibodies to toxins A and B are prevalent in
healthy populations
• Recent studies in severe disease5,6
– Well tolerated in small numbers of patients
– Conflicting data regarding outcome improvement
(mortality and need for colectomy)
• Often administered when surgery is considered imminent
1. Salcedo J, et al. Gut 1997;41:366-370. 4. Kyne L, et al. Lancet. 2001;357:189-193.
2. Beales ILP. Gut. 2002;51:456. 5. McPherson S, et al. Dis Colon Rectum. 2006;49:640-645.
3. Kyne L, et al. N Engl J Med. 2000;342:390-397. 6. Juang P, et al. Am J Infect Control 2007;35:131-137.
 Multiple Recurrent CDI
• Rates of recurrent CDI
– 20% after first episode1
– 45% after first recurrence2
– 65% after two or more recurrences3
• Metronidazole or vancomycin resistance after
treatment not reported
• Repeated, prolonged courses of metronidazole not
recommended (risk for peripheral neuropathy)
• Several empirical approaches have been advocated
but most have no controlled data
1. Aslam S, et al. Lancet Infect Dis. 2005;5:549-557.
2. McFarland LV, et al. Am J Gastroenterol. 2002:97:1769-1775.
3. McFarland LV, et al. JAMA. 1994;271:1913-1918.
 Treatment of Recurrent CDI
• First recurrence can be treated in the same way
as a first episode according to disease severity1
• Metronidazole should not be used beyond first
recurrence or for >14 days2
– Concerns for hepatotoxicity and
polyneuropathy
• Further recurrences can be treated with oral
vancomycin taper and/or pulse dosing2,3

1. Gerding DN, et al. Infect Control Hosp Epidemiol. 1995;16:459-477.

2. McFarland LV, et al. Am J Gastroenterol 2002;97:1769-1775.
3. Tedesco FJ, et al. Am J Gastroenterol. 1985;80:867-868.
 Other Treatments

IVIG* Probiotics

Rifaximin
Nitazoximide
Chasers

Rifampin

* Patients who produce antibody to toxins A and B usually do well so IVIG has been
tried.
Unproven Adjunctive Therapies
for Recurrent CDI
Probiotics
Saccharomyces boulardii May reduce the likelihood of further recurrences in some
Lactobacillus GG patients when added to and continued after treatment
with metronidazole or vancomycin1-3
Rifampin Efficacy in one series (n=7) when added to vancomycin4
Nitazoxanide Response demonstrated in patients (n=35) who failed
prior metronidazole therapy5 and similar response and
recurrence rates when compared with metronidazole for
initial therapy (n=110)6
Rifaximin “chaser” Effective when used for 14 days after vancomycin therapy
(n=8)7

1. McFarland LV, et al. JAMA. 1994;271:1913-1918.

2. McFarland LV. J Med Microbiol. 2005;54:101-111.
3. Surawicz CM, et al. Clin Infect Dis. 2000;31:1012-1017.
4. Buggy BP, et al. J Clin Gastroenterol. 1987;9:155-159.
5. Musher DM, et al. J Antimicrob Chemother. 2007;59:705-710.
6. Musher DM, et al. Clin Infect Dis. 2006;43:421-427.
7. Johnson S, et al. Clin Infect Dis. 2007;44:846-848.
Saccharomyces boulardii for CDI Prevention*

Recurrent CDI S. boulardii

P=0.04

*Metronidazole or vancomycin for 10–14 days plus placebo or S. boulardii 1 g daily × 4 weeks.
1. McFarland. JAMA. 1994;271:1913-1918.
2. Surawicz et al. Clin Infect Dis. 2000;31:1012-1017.
Recurrent CDI: Rifaximin Chaser
• Eight women with multiple recurrences
– Rifaximin 400 mg BID for 2 weeks immediately
after completing last course of vancomycin
– Seven of eight patients had no further diarrhea
recurrence
– Single case of rifaximin resistance (identified
after therapy) with recurrent CDI after a second
course of rifaxmin
• Effective in interrupting recurrent episodes
but resistance may become an issue
Johnson S, et al. Clin Infect Dis. 2007;44:846-848.
 Recurrent CDI: Fecal
Transplantation
• Rationale: restoration of bacterial homeostasis
• Preparation of donor specimen
– Fresh (<6 hours)
– ~30 g or ~2 cm3 volume
– Add 50 mL 0.9% normal saline, and homogenize with
blender
– Filter suspension twice with paper coffee filter
• Delivered by nasogastric tube following vancomycin
• Results
– 1 of 16 survivors had a single subsequent recurrence

Aas J, et al. Clin Infect Dis. 2003;36:580-585.

 Infection Control
• Wash hands with warm soap and water
– Mechanical removal of spores
– Alcohol does not kill spores
– Stool is pre-treated with alcohol when growing
C. difficile
• Contact and barrier precautions
• Private room
• Antibiotic stewardship
Efficacy of Hand Hygiene Methods for Removal
of C. difficile Contamination from Hands
Decrease in colony counts WWS = warm
water and soap
compared with no wash
2.5 CWS = cold
water and soap
2
WWA = warm
Decrease in colony counts

1.5 water and

(log CFU/mL)

antibacterial
1
1.8 1.8 AHW = alcohol
1.4
0.5 hand wipe

0 ** ** * *0.6 -0.1
AHR = alcohol
hand rub
-0.5

-1
WWS CWS WWA AH AHR
W
Hand hygiene method
CFU = colony forming units
* Different from AHR (P<0.05).
Oughton M, et al. The 47th Annual ICAAC Meeting, 2007. ** Different from AHR and AHW (P<0.05)
Alcohol Gels and Hand Hygiene
• Alcohol-based gels appear to be less able to remove
C. difficile spores
• However, in general they:
– Provide an excellent method of hand hygiene effective
against many common nosocomial pathogens
– Are convenient thereby increasing compliance
– Have not been implicated in CDI outbreaks
• In the setting of a CDI outbreak or increased rates,
visitors and healthcare workers should wash hands
with soap and water after caring for patients with
C. difficile
CDC. Fact Sheet, August 2004 (updated 7/22/05).
Oughton M, et al. The 47th Annual ICAAC Meeting, Sept. 17-20, 2007; Chicago, IL.
Isolation and Barrier Precautions

• Patients with CDI and incontinence should

be in private rooms or cohorted if private
rooms are not available
• Contact precautions and isolation
– Gloves and gowns required for direct contact and
contact with environment
– Discontinuation of isolation when diarrhea resolves
• Dedicated equipment when possible
CDC Guideline for Isolation Precautions, 2007.
Gerding DN, et al. Infect Control Hosp Epidemiol. 1995;16:459-477.
Simor AE, et al. Infect Control Hosp Epidemiol. 2002;23:696-703.
 Environmental Disinfection
• Removal/thorough cleaning of environmental
sources can decrease incidence
• Use chlorine-containing agents (at least
5000 ppm available chlorine 10 minutes contact
time) for environmental contamination, especially
in outbreak areas
• Fogging

Poutanen SM, Simor AE. Can Med Assoc J. 2004;171:51-58.

CDC. Fact Sheet, July 2005.
McMullen KM, et al. Infect Control Hosp Epidemiol. 2007;28:205-207.
Mayfield JL, et al. Clin Infect Dis. 2000;31:995-1000.
Fawley WN, et al. Infect Control Hosp Epidemiol. 2007;28:920-925.
 Antimicrobial Use Restrictions
• Practice antimicrobial stewardship
• Decrease duration of exposure and number
of antimicrobial agents
• Best evidence for controlling C. difficile
demonstrated with restriction of
cephalosporin or clindamycin
• Recent reports of fluoroquinolone restriction
helping to control outbreaks
McNulty C, et al. J Antimicrob Chemother. 1997;40:707-711.
Pear SM, et al. Ann Intern Med. 1994;120:272-277.
Climo MW, et al. Ann Intern Med. 1998;128:989-995.
Kallen AJ, et al. Infect Control Hosp Epidemiol. 2009;30:264-72.
 Summary
• CDI is increasing in incidence, severity and poor
outcomes
• Laboratory diagnosis is challenging
– Carefully evaluate what works best in your setting
• No reasonable explanation for treatment failures
• Community based infections are not well
understood
• Improved therapies are needed
• Extremely important to accurately detect and
aggressively treat severe disease
 Y Chromosome
Gitschier, J., Science, 1993 (261) p. 679

Testis Determining Factor (TDF)

10.3 Gadgetry (MAC- locus)
Channel Flipping (FLP)
10.5
p Catching and Throwing (BLZ-1)
Self-confidence (BLZ-2)
10.7
(note: unlinked to ability)
11.0 Ability to remember and tell jokes (GOT-1)
Sports Page (BUD-E)
11.1 Addiction to death & destruction
movies (MOV-E)
q Air Guitar (RIF)
11.5 Ability to identify aircraft (DC10)
Pre-adolescent fascination with Arachnid
and Reptilia (MOM-4U)
11.8
Spitting (P2E)
12.0 Sitting on the john reading (SIT)
Inability to express emotion over the
phone (ME-2)
Selective hearing loss (HUH?)
Total lack of recall for dates (OOPS)
Thank you