Tres Difficile

Stephen M. Brecher PhDDirector of Microbiology

VA Boston Health Care SystemWest 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 (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”

PathogenesisHistorical 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

Asymptomatic C. difficile colonization

Pathogenesis of CDI

C. difficile exposure

Antimicrobial

C. difficile infectionHospitalization

From Johnson S, Gerding DN. Clin Infect Dis. 1998;26:1027-1036; with permission.

PathogenesisChanging 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;44:238-244.3. CDC Fact Sheet. July 2005. 4. 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;366:1079-1084, 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 implicated1. 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

Laboratory Laboratory DiagnosisDiagnosis

Enzyme Immunoassay (EIA)Enzyme Immunoassay (EIA)Glutamate Glutamate

Dehydrogenase (GDH)Dehydrogenase (GDH)Cell Culture Cell Culture

Neutralization Neutralization Assay (CCNA)Assay (CCNA)

Toxigenic Culture Toxigenic Culture (Culture and CCNA)(Culture and CCNA)

Molecular Based (PCR Or LAMP)Molecular Based (PCR Or LAMP)

Stool CultureStool Culture

Conflicting Results with EIA

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

Recently Published EIA Papers(1-6)

Parameter Range

Sensitivity 32 – 98.7%

Specificity 92 – 100%

PPV 76.4 – 96%

NPV 88 – 100%

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 Tests1-3

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 low-

prevalence population• EIA: Is it accurate enough

to use as a screening test? Confirmatory test?

Confirmatory Tests• CCNA

– Add 1-2 days• CX followed by CCNA

– Add 3-4 days• PCR

– Possibility of false positives due to colonization

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 ofMild 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

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

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

Defining CDI Disease Severity

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

Any one of the 3 defining characteristics assigns a patient to the more severe category.

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.

• 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.

Management of Severe, Complicated CDI

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

* Patients who produce antibody to toxins A and B usually do well so IVIG has been tried.

Probiotics

Rifaximin Chasers

Rifampin

Nitazoximide

IVIG*

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*

1. McFarland. JAMA. 1994;271:1913-1918. 2. Surawicz et al. Clin Infect Dis. 2000;31:1012-1017.

PP=0.04=0.04

*Metronidazole or vancomycin for 10–14 days plus placebo or S. boulardii 1 g daily × 4 weeks.

Rec

urr

ent

CD

IS. boulardii

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.

• 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

Recurrent CDI: Fecal Transplantation

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

CFU = colony forming units* Different from AHR (P<0.05).** Different from AHR and AHW (P<0.05)

*

WWS = warm water and soap

CWS = cold water and soap

WWA = warm water and antibacterial

AHW = alcohol hand wipe

AHR = alcohol hand rub

Decrease in colony countscompared with no wash

1.8 1.81.4

0.6

-0.1

-1

-0.5

0

0.5

1

1.5

2

2.5

Hand hygiene method

Dec

reas

e in

col

ony

cou

nts

(l

og C

FU

/mL

)

WWS CWS WWA AHW AHR

** ** *

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

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

11.5

10.7

10.5

10.3

12.0

11.1

11.0

11.8

q

p

Y Chromosome

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)

Gitschier, J., Science, 1993 (261) p. 679

Thank you