Clostridium Difficile Epidemiology

7/21/2019 Clostridium Difficile Epidemiology

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Clostridium diffic

ISHA BHATT

DEPARTMENT OF EPIDEMIOLOGY AND BIOSTATISDREXEL UNIVERSITY SCHOOL OF PUBLIC HEA

MAY, 2014


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OverviewClinical context and terminologyMicrobiology

Pathogenesis and reservoirs

Disease definition, syndromes , outcomes

Diagnosis and treatmentSurveillance and prevention strategies

Impact


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History:First cases of C.diff infections reported as far back as 1890sFirst isolated in the stools of infants and described by Hall aOToole in 1935 as Bacillus difficile.

In 1978, Bartlett et al, demonstrated a link between C.diff tcases of pseudomembranous colitis after antibiotic use.

The years 20032005 saw several outbreaks in Canada anKingdom

2004First International Clostridium difficile symposium(F


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cro o ogy Gram positive

Motile ,obligate

anaerobe Spore and Toxin

producing

Normal gut floraespecially in

infants andelderly

Multiple strains

Also known asC.diff

Source: http://www.bioquell.com/technology/microbiology/clostridium-diffic


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Culture : Isolation MedCCFA: first proposedBA with lysed horse blood:Opaque grey-white colonies

TCCFA: Enhances sporulation

CDMN Selective Agar: C.difficile grows better

Buchanensbroth


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Terminology:Antibiotic-associated diarrhea : C.diff is only one of the etfactors (10%-25%). Others include MRSA, Klebsiella, E.coli in

Clostridium difficile infections (CDI) : diarrhea associated positive stool culture and toxin assays

Clostridium difficile associated diarrhea (CDAD): used

interchangeably with CDI.Pseudomembranous colitis: fulminant CDI, severe and oftConfirmed endoscopically

Toxic megacolon: also diagnosed by CT and endoscopy. Mperforation and death


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Reservoir :~2% normal adult gut flora

1070% colonization in newborns and infants (50%)

Exogenous reservoir : animals feces

Spores : highly resistant to destruction and disinfection

Most acquired disease causing strains are in hospital settingthrough HCW hands

Increased colonization rates in hospitalized patients or thosterm care facilities after antibiotic exposure (10- 25 %)


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Risk Factors :Patients in hospitals and long-term care facilitExposure to antibiotics

Elderly

Children >1 yearPeripartum women

History of Inflammatory bowel diseases


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Antibiotics implicatedHigh Frequency Medium frequency Low Freq

Ampicillin Erythromycin Chloramphe

Amoxicillin Other macrolides Metronidazo

Clindamycin Sulphonamides Rifampin

Fluoroquinolones Tetracycline

Cephalosporins Vancomycin


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Transmission:Primary mode of transmission:Fecal-Oral route

Direct contact: Hands of healthcare workers

Patient to patient transmission

Family and/or visitor introduction

Asymptomatic carriers

Indirect transmission via fomitesProcedural transmission:through improperly sterilizedrectal thermometers andendoscopic tubes and intubation


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CDI : Symptoms

CDI have a wide range of clinical presentationIngestion of C.diff may lead to excretion or asymptocolonization of healthy individuals

Manifested disease may be mild, moderate to sever

life-threatening consequencesRelapses are not uncommon in healthcare settings

Mild t M d t S


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Mild to Moderate cases Severe case

Fever Pain, fever, diarrhea, inc

Abdominal pain Blood in stool

Diarrhea (>10 bowel movements

per day)

Electrolyte imbalance

Increased WBCs Paralytic ileus

Dehydration Toxic megacolon

Pseudomembranous co

Perforation

Death


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Pathogenesis:Disruption of normal protective gut flora

Ingestion of spores and colonization of C.dif

Toxin production A and B

Damage to the cytoskeletal structures, loss of t

junctions leading to mucosal injury , inflammat

increased fluid secretion

Colitis and diarrhea


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Onset and Progressio

Source: http://www.cdc.gov/HAI/pdfs/cdiff/Cohen-IDSA-SHEA-CDI-guidelines-2010.pdf


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Course :Onset usually >3 days - ~7 daysLatent period difficult to determine due toasymptomatic carriers

Acute infection lasts for more than 10 days an

continues depending on severity and extent ofmucosal damage

Infection may progress to complete resolutionrecurrence or in severe cases coma or death

C d fi i i I id


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Case definition: Incide

Presence of symptoms (usually diarrheai.e >10 bomovements per day)

AND

Either Stool test result positivefor C. difficile toxins or tC. difficile

ORor colonoscopic evidence of pseudomembranous c

Source : http://www.cdc.gov/HAI/pdfs/cdiff/Cohen-IDSA-SHEA-CDI-guidelines-2010.pdf


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Probable case: prompt to isolaand testConsider presumptive isolation for patients with > 3 unformed swithin 24 hours

Send specimen for testing and presumptively isolate patient peresults

Positive predictive value of testing will also be optimized if focpatients with >3 unformed stools within 24 hours

Exception: patient with possible recurrent CDI (isolate and testfirst unformed stool)

Source : CDC SHEA Guildelines, 2012

Di i L b t


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Diagnosis : LaboratoryTestingTissue Culture Cytotoxin Assay : Gold standard to identify toxinsamples in Vero cells

Toxigenic Culture 4-6 isolates to CMC

24 hr. filtrate for toxin detection ( fast )

Enzyme Immunoassay for toxin detection ( Toxin A and B )

Glutamate dehydrogenase detection : characteristic enzyme prby C.diff

PCRtoxin gene detection, greater sensitivity and specificity

Li it ti t L b t


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Limitations to Laboratortesting:Cytotoxin assays have low sensitivity and specificityStool culturetime-consuming

GDH : risk of cross reaction

Recommendation for best predictive outcome :

-Screening for GDH

-Followed by culture for C.diff or EIA toxin assay


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Radiologic testing :

Accordion Signevidence ofPseudomembracolitis

E d i T ti


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Endoscopic Testing :Colonoscopy

Evidence suggeof PMC


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Treatment :

Discontinue the offending agentstop the antimitreatment !!

Start supportive treatment simultaneously : Fluid symptomatic treatment

If not resolved with conservative therapyStart or

metronidazole for 10 days or VancomycinWhen both vancomycin and metronidazole fail : acombination therapy


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:Probioticsefficacy undetermined

Fecal micro biota transplant : risk of transplantother pathogens

IV immunoglobulinspassive immunizationespecially for Immunocompromised

Surgical approach : in severe fulminant casesresection of necrotic colon to prevent sepsis

New Antibiotic: Fidaxomycin

reven on: ore


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reven on: orestrategies Judicious use of high potency antibiotics Contact Precautions for duration of diarrhea

Hand hygiene in compliance with CDC/WHO

Cleaning and disinfection of equipment and envir

Laboratory-based alert system for immediate notof positive test results

Educate about CDI: HCP, housekeeping, administrpatients, familiesSource: http://www.cdc.gov/ncidod/dhqp/id_CdiffFAQ_HCP.html

Dubberke et al. Infect Control Hosp Epidemiol 2008;29:S81-92

Prevention: Supplement


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Prevention: SupplementstrategiesExtend use of Contact Precautions beyond duration of diarrhe48 hours)

Presumptive isolation for symptomatic patients pendingconfirmation of CDI

Evaluate and optimize testing for CDI : for faster and accuratdiagnosis

Implement soap and water for hand hygiene before exiting patient with CDI

Implement universal glove use on units with high CDI rates

Use sodium hypochlorite (bleach)for spores


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CDI : Incidence and Epidemiolog(US)Increased incidence (2.7 cases per

1,000 discharges in 1997 to 6.8 casesper 1,000 discharges in 2001)

Increased severity (0.15 to 0.60 casesper 1,000 discharges) of CDI

23% annual increase in CDI-related

hospitalizations between 2000 and2005, associated with an increasedage-adjusted, annual case-fatality rateof 0.2% over the study period

Changing trends and


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Changing trends andcauses:The proportion of children with toxin-positive stool increased from 46% in 2001 to 64% in 2006.

Prior to 1990, predominant strain was toxinotype0/ribotype 001

Now: ribotype 027 (BI/NAP1/027) is associated with

increased virulence, mortality and morbidityIncrease incidence in previously considered non-higgroups


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Surveillance :

To layout case definitions for Healthcare facilitacquired CDI and community acquired CDI

Use these as universal guidelines to survey thdisease in populations across the country and

worldDevise prevention strategies to curb the epide

Surveillance and


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Surveillance andreporting :

EIP : Emerging Infections program - surveillanrepresentative of the whole country.

NHSN : National Healthcare Safety Networkentered from hospitals

HHS Action Plan : targets towards reducing HAincluding CDI


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Impact on Health care

CDI may have resulted in $4.8 billion excess costs in US acute-care facilities

Per person cost increases by $2000- $due to prolonged hospital stay andadditional testing

Increased risk of recurrence


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Global impactNew MRSA

Similar increase in CDI worldwideacross North AEurope and Asia

New strain in Asia O17 in addition to O27

Globally difficult surveillance : no universal case

definitions, diagnostic gold standards, inadequate reporting ad collection

Ongoing research and cumulative efforts to comba

References :


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References:Bartlett, J. G., & Gerding, D. N. (2008). Clinical recognition and diagnosis of clostridium dinfection.Clinical Infectious Diseases, 46(Supplement 1), S12-S18. doi:10.1086/521863

Centers for Disease Control and Prevention (CDC). (2012). Vital signs: Preventing clostridinfections.MMWR.Morbidity and Mortality Weekly Report, 61(9), 157-162. doi:mm6109

Cohen, S. H., Gerding, D. N., Johnson, S., Kelly, C. P., Loo, V. G., L Clifford McDonald, M., .H. (2010). Clinical practice guidelines for clostridium difficile infection in adults: 2010 upsociety for healthcare epidemiology of america (SHEA) and the infectious diseases socie(IDSA).Infection Control and Hospital Epidemiology, 31(5), 431-455.

HALL, I. C., & O'TOOLE, E. (1935). Intestinal flora in new-born infantswith a description opathogenic anaerobe, bacillus difficilis.American Journal of Diseases of Children,49(2), 3

Kelly, C. P., & LaMont, J. T. (2008). Clostridium difficilemore difficult than ever.New Enof Medicine, 359(18), 1932-1940.

L Clifford McDonald, M., Coignard, B., Dubberke, E., Song, X., Horan, T., Kutty, P. K., & AdClostridium difficile Surveillance Working Group. (2007). Recommendations for surveillaclostridium difficileassociated disease.Infection Control and Hospital Epidemiology, 28(

Lessa, F. C., Gould, C. V., & McDonald, L. C. (2012). Current status of clostridium difficile epidemiology.Clinical Infectious Diseases : An Official Publication of the Infectious DiseaAmerica, 55 Suppl 2, S65-70. doi:10.1093/cid/cis319 [doi]


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Thank you

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Clostridium Difficile Epidemiology