What’s All the Fuss About What’s All the Fuss About Clostridium difficileClostridium difficile??

Peter C. Iwen, PhD, D(ABMM)Peter C. Iwen, PhD, D(ABMM)

Nebraska Public Health LaboratoryNebraska Public Health Laboratory

Clostridium difficileClostridium difficile – GI – GI DiseaseDisease

Indigenous microflora of colonIndigenous microflora of colon1 trillion bacteria per gram!1 trillion bacteria per gram!

ObjectivesObjectives

C. difficileC. difficile ….the organism ….the organism Host relationships and Host relationships and

pathogenesispathogenesis DiagnosisDiagnosis Prevention and controlPrevention and control Patient managementPatient management Update clinical issuesUpdate clinical issues

National Estimates of US Short-Stay Hospital Discharges with C. difficile as

First-Listed or Any Diagnosis

From McDonald LC, et al. Emerg Infect Dis. 2006;12(3):409-15

Clostridium difficileClostridium difficile BacteriumBacterium

– AnaerobeAnaerobe– Gram-positive spore-Gram-positive spore-

forming bacillusforming bacillus SourceSource

– Environment Environment – Stool floraStool flora

Host RelationshipHost RelationshipDisturbed colonic Disturbed colonic microfloramicroflora↓↓C. difficileC. difficile exposure & exposure & colonizecolonize↓↓Toxin A & BToxin A & B↓↓Diarrhea & colitisDiarrhea & colitis

Risk FactorsRisk Factors Age >65 yearsAge >65 years Severe underlying disease Severe underlying disease

– Prompting hospitalizationPrompting hospitalization Nasogastric intubationNasogastric intubation Antiulcer medications Antiulcer medications

– Proton pump inhibitorsProton pump inhibitors Antimicrobial therapyAntimicrobial therapy

– Clindamycin, 3Clindamycin, 3rdrd generation cephalosporins, generation cephalosporins, penicillin, fluoroquinolonespenicillin, fluoroquinolones

Long hospital stay or long-term care Long hospital stay or long-term care residencyresidency

““Clostridium difficileClostridium difficile is the most common is the most common cause of nosocomial infectious diarrhea.”cause of nosocomial infectious diarrhea.”

Sunenshine andSunenshine andMcDonald, McDonald, ClevelandClevelandClin. J. Med.,Clin. J. Med.,Feb 2006Feb 2006

Virulence FactorsVirulence Factors Toxin A Toxin A

– ExotoxinExotoxin– Enterotoxic to cellsEnterotoxic to cells

Toxin BToxin B– ExotoxinExotoxin– Not as toxic to cells?Not as toxic to cells?

Multiple strains of Multiple strains of C. difficileC. difficile– ToxA+/ToxB+ToxA+/ToxB+– ToxA+/ToxB-ToxA+/ToxB-– ToxA-/ToxB+ToxA-/ToxB+

……only toxigenic strains of only toxigenic strains of C. difficileC. difficile produce disease…produce disease…

CDI vs CDI vs Antibiotic-Associated Antibiotic-Associated

DiarrheaDiarrhea

Clinical PresentationClinical Presentation

Mild diseaseMild disease– Non-bloody diarrheaNon-bloody diarrhea– Mild abdominal tendernessMild abdominal tenderness

Severe diseaseSevere disease– Pseudomembranous colitisPseudomembranous colitis– Paralytic ileusParalytic ileus

IleitisIleitis– Toxic megacolonToxic megacolon

Ulcerative colitisUlcerative colitis– PerforationPerforation– AscitesAscites

Pseudomembranous Pseudomembranous ColitisColitis

H & E, OM 400xH & E, OM 400x

Mushroom-shaped pseudomembraneMushroom-shaped pseudomembrane→→““Volcano” lesionVolcano” lesion

Yellow lesion against Yellow lesion against hyperemic bowelhyperemic bowel

DiagnosisDiagnosis

DiagnosticsDiagnostics Generally….Generally….

……if stool samples are obtained after hospital day if stool samples are obtained after hospital day 3, the only enteric pathogen most labs will test for 3, the only enteric pathogen most labs will test for is…..is…..Clostridium difficileClostridium difficile…..…..

Testing not considered a STAT testTesting not considered a STAT test– Batching, but calling all positive resultsBatching, but calling all positive results

Many labs will only test a diarrheic stool specimenMany labs will only test a diarrheic stool specimen

Follow-up testing of previous positive result not Follow-up testing of previous positive result not usefuluseful– Patients remain positive for monthsPatients remain positive for months– Not useful for “proof-of-cure”Not useful for “proof-of-cure”

85%-97%85%-97%

Relative SensitivityRelative Sensitivity

Culture >Culture >

Cell cytotoxin >Cell cytotoxin >

Toxin A & B EIA >Toxin A & B EIA >

Toxin A EIA >Toxin A EIA >

Latex agglutination >Latex agglutination >

EndoscopyEndoscopy

What about PCR?What about PCR?

Studies have shown PCR to be less Studies have shown PCR to be less sensitive than the toxin assaysensitive than the toxin assay– Requires a nucleic acid extraction Requires a nucleic acid extraction

stepstep Complexity of stool matrix a problemComplexity of stool matrix a problem

CDI Case DefinedCDI Case Defined

Stool characteristicStool characteristic– Diarrhea (most common)Diarrhea (most common)– No diarrheaNo diarrhea

Associated with toxic megacolon or ileitisAssociated with toxic megacolon or ileitis– Documented by radiologyDocumented by radiology

≥ ≥ 11 of the following of the following– Stool positive for:Stool positive for:

C. difficileC. difficile toxin toxin C. difficileC. difficile determined to be a toxin producer determined to be a toxin producer

– Pseudomembranous colitis by: Pseudomembranous colitis by: EndoscopyEndoscopy Histological examHistological exam

Prevention and ControlPrevention and Control

Prevent ingestion of the organismPrevent ingestion of the organism– Infection control strategiesInfection control strategies

Target environmentTarget environment Personal hygienePersonal hygiene Barrier methodsBarrier methods

Reduce the chance of disease in the Reduce the chance of disease in the event of such digestionevent of such digestion– Minimize or eliminate antibiotic Minimize or eliminate antibiotic

exposureexposure ““Good antimicrobial stewardship”Good antimicrobial stewardship”

Audience InteractionAudience Interaction

Clostridium difficileClostridium difficile spores can spores can resist desiccation and can persist resist desiccation and can persist on hard surfaces:on hard surfaces:

A.A. 48 hours or less48 hours or less

B.B. About 1 weekAbout 1 week

C.C. About 1 monthAbout 1 month

D.D. > 6 months> 6 months

The most effective cleaning agent for The most effective cleaning agent for killing killing C. difficileC. difficile spores in the spores in the environment is:environment is:

A.A. 70% alcohol70% alcohol

B.B. 10% bleach10% bleach

C.C. Hot water and soapHot water and soap

D.D. Phenol solutionsPhenol solutions

E.E. Quaternary ammonium compoundsQuaternary ammonium compounds

Enhanced environmentalEnhanced environmentalcleaning…sporocidalcleaning…sporocidal

The incubation period for The incubation period for Clostridium difficileClostridium difficile infection is: infection is:

A.A. Less than 1 dayLess than 1 day

B.B. 1-7 days1-7 days

C.C. 2-3 weeks2-3 weeks

D.D. UnknownUnknown

Barrier precautions to prevent Barrier precautions to prevent the spread of the spread of Clostridium difficileClostridium difficile include:include:

A.A. Airborne precautionsAirborne precautions

B.B. Droplet precautionsDroplet precautions

C.C. Contact precautionsContact precautions

D.D. Standard precautions onlyStandard precautions only

Single roomSingle roomGlovesGlovesGownsGowns

Duration of isolation controversialDuration of isolation controversial……2 days after diarrhea resolves2 days after diarrhea resolves……upon dischargeupon discharge

Patient ManagementPatient Management

Surgical consult…perforation, toxic megacolon,Surgical consult…perforation, toxic megacolon,colonic-wall thickening, ascites….colonic-wall thickening, ascites….

““Stool infusion therapy” or “fecal transplant” has been Stool infusion therapy” or “fecal transplant” has been shown to be highly effective….shown to be highly effective….

Update Clinical IssuesUpdate Clinical Issues

Hypervirulent Hypervirulent C. difficileC. difficile strain strain Community-associated CDICommunity-associated CDI Proton Pump Inhibitors as risk Proton Pump Inhibitors as risk

factorfactor– Antacids and antiulcer drugsAntacids and antiulcer drugs

Medicare issues and CDIMedicare issues and CDI

Hypervirulent CDIHypervirulent CDI

Hypervirulent Hypervirulent C. C. difficiledifficile Strain Strain

North American PFGE Type 1North American PFGE Type 1

Restriction enzyme analysis Type BIRestriction enzyme analysis Type BI

PCR ribotype 027PCR ribotype 027

Collectively referred to as “NAP1/BI/027 Collectively referred to as “NAP1/BI/027 strain”strain”

NAP1 Virulence NAP1 Virulence AttributesAttributes

HypertoxigenicHypertoxigenic– Toxin AToxin A 16x16x– Toxin BToxin B 23x23x– Binary toxinBinary toxin

Hypersporulation capacityHypersporulation capacity High-level resistance to High-level resistance to

fluoroquinolonesfluoroquinolones– Leads to outbreaksLeads to outbreaks

States with the Epidemic Strain of States with the Epidemic Strain of C. C. difficiledifficile Confirmed by Confirmed by CDCCDC and and Hines VA Hines VA

labslabs (N=24), (N=24),Updated 2/9/2007Updated 2/9/2007

DC

PRAK

HI

Community-Acquired Community-Acquired CDICDI

Less common than nosocomialLess common than nosocomial

No traditional risk factorsNo traditional risk factors– ““Spontaneous”Spontaneous”

Exposure to hypervirulent strainExposure to hypervirulent strain

More likely to receive antacids (anti-ulcer) More likely to receive antacids (anti-ulcer) drugsdrugs

Heartburn Drugs Cause Heartburn Drugs Cause Diarrhea?Diarrhea?

Proton pump inhibitorsProton pump inhibitors– PrilosecPrilosec– PrevacidPrevacid– NexiumNexium

H2 blockersH2 blockers– ZantacZantac– PepcidPepcid– TagametTagamet

Main function is to suppress stomach acid productionMain function is to suppress stomach acid production– GastritisGastritis– GERD (acid reflux disease)GERD (acid reflux disease)– HeartburnHeartburn

S. Dial, 2005, J. Amer. Med Assoc., 293:2989-2995.S. Dial, 2005, J. Amer. Med Assoc., 293:2989-2995.

Stomach Acid-Suppressing Stomach Acid-Suppressing Medications and Community-Acquired Medications and Community-Acquired

CDAD, EnglandCDAD, England

From Dial S, et al. JAMA. 2005;294:2989-2995.

Deficit Reduction Act of Deficit Reduction Act of 20052005

Requires an adjustment in Requires an adjustment in Medicare Diagnosis Related Group Medicare Diagnosis Related Group paymentspayments

– For certain hospital-acquired For certain hospital-acquired

conditionsconditions

““Myth Busters”Myth Busters”

C. difficileC. difficile may infect individuals who are may infect individuals who are NOTNOT taking antibiotics taking antibiotics

Optimal method to diagnose CDI is Optimal method to diagnose CDI is NOTNOT clearclear

Alcohol-based gels are Alcohol-based gels are NOTNOT effective for effective for hand hygiene against hand hygiene against C. difficileC. difficile spores spores

Vancomycin is Vancomycin is NOTNOT the recommended the recommended initial therapy for CDIinitial therapy for CDI

Current literature does Current literature does NOTNOT support the support the use of probiotics to treat for CDIuse of probiotics to treat for CDI

CDI is CDI is NOTNOT only a problem in acute care only a problem in acute care hospital facilities but also long-term care hospital facilities but also long-term care and rehab centersand rehab centers

Recommendations for Recommendations for ControlControl

Conduct surveillance for Conduct surveillance for CDICDI

Early diagnosis and Early diagnosis and treatmenttreatment

Strict infection control Strict infection control practicespractices

Good antimicrobial Good antimicrobial stewardshipstewardship

Clostridium difficileInfection

QuestionsQuestions????