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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


1013 human cells and
a minimum of 1014
bacterial cells

Overview
Case reports
Historical
perspective
Organism & key
properties

Changing
epidemiology
Disease
Diagnosis
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 (contd)


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 (contd)


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 OToole 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 (contd)


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 inpatient 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

Hospitalization

C. difficile
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

1.
2.
3.
4.

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

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


Hubert B, et al. Clin Infect Dis. 2007;44:238-244.
CDC Fact Sheet. July 2005.
McDonald LC, et al. N Engl J Med. 2005;353:2433-2441.

Adapted from McDonald LC, et al. N Engl J Med. 2005;353:2433-2441; with


permission.

In Vitro Production of Toxins


in Epidemic Strain

From Warny M, et al.


Lancet. 2005;366:10791084, 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 4C for up to 3 days
Freeze at -70C (not -20C) if testing will
be delayed
Specimen quality will influence test results
In: Manual Clin Micro. 9th ed. 2007;p. 897.

Laboratory Diagnosis of CDI


Glutamate
Dehydrogenase (GDH)

Toxigenic Culture
(Culture and CCNA)

Enzyme Immunoassay (EIA)

Laboratory
Diagnosis

Cell Culture
Neutralization
Assay (CCNA)

Stool Culture

Molecular Based (PCR Or LAMP)

Conflicting Results with EIA


Recently Published EIA Papers(1-6)

1.
2.
3.
4.
5.
6.

Parameter

Range

Sensitivity

32 98.7%

Specificity

92 100%

PPV

76.4 96%

NPV

88 100%

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


Musher DM, et al. J Clin Microbiol. 2007;45:2737-2739.
Sloan LM, et al. J Clin Microbiol. 2008;46:1996-2001.
Gilligan PH. J Clin Microbiol. 2008;46:1523-1525.
Ticehurst JR. J Clin Microbiol. 2006;44:1145-1149.
Nice review by Planche T, et al. 2008. www.thelancet.com/infection

EIA Testing

Advantages
Rapid
Inexpensive
Relatively easy
No costly equipment
Batch or single test
formats

Disadvantages
Great variations in
published sensitivity
and specificity
Technologist error
Contamination

Two-Step Tests
Screening Tests
Glutamate dehydrogenase
(GDH)
Detects nearly all true
positives as well as false
positives
Low PPV
High sensitivity
Very few false negatives

Works best in a lowprevalence 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

1-3

Confirmatory Tests
CCNA
Add 1-2 days

CX followed by CCNA
Add 3-4 days

PCR
Possibility of false positives
due to colonization

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
520% 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
250 mg QID or
500 mg TID

May be administered PO or IV
Development of resistance rare
Historical first-line agent

Vancomycin
125 mg QID

Effective in enteral (oral or rectal) form only


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

35 BM/day
WBC 15,000/mm3
Mild abdominal pain due to CDI

Moderate CDI

69 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 714 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.
B.
C.
D.

Await stool test results and monitor her progress


Empirically start metronidazole PO
Empirically start metronidazole IV
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 714 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.
B.
C.
D.

Await stool test results and monitor her progress


Empirically start metronidazole PO
Empirically start metronidazole IV
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)
0.51 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 412 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.
2. Beales ILP. Gut. 2002;51:456.
3. Kyne L, et al. N Engl J Med. 2000;342:390-397.

4. Kyne L, et al. Lancet. 2001;357:189-193.


5. McPherson S, et al. Dis Colon Rectum. 2006;49:640-645.
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
Chasers

Nitazoximide
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
Lactobacillus GG

May reduce the likelihood of further recurrences in some


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 1014 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
compared with no wash

WWS = warm
water and soap
CWS = cold
water and soap

2.5

Decrease in colony counts


(log CFU/mL)

WWA = warm
water and
antibacterial

1.5
1

1.8

1.8

0.5
0

AHW = alcohol
hand wipe

1.4

** ** *

*0.6

-0.1

AHR = alcohol
hand rub

-0.5
-1

WWS

CWS

WWA

AHW AHR

Hand hygiene method


Oughton M, et al. The 47th Annual ICAAC Meeting, 2007.

CFU = colony forming units


* Different from AHR (P<0.05).
** 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

10.3
10.5

10.7
11.0
11.1

q
11.5

11.8
12.0

Testis Determining Factor (TDF)


Gadgetry (MAC- locus)
Channel Flipping (FLP)
Catching and Throwing (BLZ-1)
Self-confidence (BLZ-2)
(note: unlinked to ability)
Ability to remember and tell jokes (GOT-1)
Sports Page (BUD-E)
Addiction to death & destruction
movies (MOV-E)
Air Guitar (RIF)
Ability to identify aircraft (DC10)
Pre-adolescent fascination with Arachnid
and Reptilia (MOM-4U)
Spitting (P2E)
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