john lynch, md, mph harborview medical center university ...john lynch, md, mph. harborview medical...

John Lynch, MD, MPHHarborview Medical Center

University of WashingtonSeattle, Washington

Presented at WSHA/ASHNHA Partnership for Patients Safe Table – November 8, 2017Presented at WSHA/ASHNHA Partnership for Patients Safe Table – November 8, 2017

Why are we talking about this?

• CDI hospitalizations doubled between 2000-2010

• 14,000 deaths in the US in 2007 (an increase from 3000 in 1999)

• Excess cost of nearly $5 billion dollars for acute care facilities alone

• Leading HAI in the US right now


• Approximately 4-10% of pts colonized with toxin+ C. difficile on hospital admission

• CA-CDI increased in younger, healthier individuals

• ~48 community case/100,000 population* • Not much is working to change this….

Why are we talking about this?

Lessa, NEJM, 2015

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What is it?

• Gram-positive, anaerobic, spore-forming bacteria (Firmicutes family

• Live as vegetative and spore forms

• Spores are O2-tolerant (very hardy)

• Intrinsically drug resistant


• Ingestion of spores ≠ disease (?)• Asymptomatic, colonized individuals

may still be able to spread spores

What is it?


C. difficile: A History


C. difficile: A History

• 1935 - Hall & O’Toole in healthy neonates, “the difficult bacillus”, Bacillus difficile

• 1974 – Clindamycin-associated colitis• 1978 - Pathogenic role described by Bartlett

and colleagues as infectious cause of AAD• Recurrence?• 2005- BI/NAP1/027 & community

acquisition described


Clostridium difficile Biology

• Genetically diverse– Pathogenic, toxin-producing strains– Non-pathogenic strains

• 2 protein exotoxins disrupt colonic epithelial cells and stimulate cytokines/chemokines– TcdA (toxin A)– TcdB (toxin B)

• Toxin production leads to inflammation• Disease outcome associated with host's immune

response


Clostridium difficile Types

Lessa, NEJM, 2015

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BI/NAP1/027 & Other Clones

• Produces toxins A and B• Also produces binary toxin (C. difficile

transferase/CDT) (also 078 and 023)• Increased disease severity and 30-day mortality• Fluoroquinolone resistant• 6 centers in the US 98 ribotypes/720 samples,

Australia 32 ribotypes/70 samples• Global epidemiology is confusing

Shen. PLoS Pathogens, 2015

Maybe as little as 2 hours?


Borgia, Exp Opin Bio Therapy, 2015 Presented at WSHA/ASHNHA Partnership for Patients Safe Table – November 8, 2017

Nephron CC BY-SA 3.0 via Wikime sented at WSHA/ASHNHA Partnership for Patients Safe Table – November 8, 2017


Risk for Acquisition

• Proximity to a symptomatic case• Increasing age• Co-morbidities• Longer hospital admission• Proton pump inhibitor use• Antibiotic use (dysbiosis)


Clostridium difficile Disease

Wikipedia commonsPresented at WSHA/ASHNHA Partnership for Patients Safe Table – November 8, 2017

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CDI Classification

• Mild to moderate (no/little systemic signs)

• Severe (systemic signs of disease)• Severe, complicated

(+hypotension, ileus, megacolon)• Recurrent (within 8 weeks)


Clostridium difficile Testing

• Reference standards:– Cytotoxicity culture– Cell cytotoxicity assay (CTA)

• Toxin enzyme immunoassay (EIA), sensitivity 60-92%, specificity 98%

• Glutamate dehydrogenase, sn 90%, sp 90% (variable) - doesn't detect toxin/disease

• Nucleic acid amplification tests, sn 90%, sp96% - doesn’t detect toxin/disease


TOXIN A+

TOXIN B+

Toxin B PCR = POSITIVE

CDI?


TOXIN A+

TOXIN B+


Immunoassay = NEGATIVE

CDI?


TOXIN A+

TOXIN B+


Immunoassay = POSITIVE

CDI?


Clostridium difficile Algorithm 1


Clostridium difficile Algorithm 2


Recurrent CDI

• Very big problem• Recurrent disease not worse than primary

infection• As high as 25% of treated patients have a

recurrence within 30 days• Higher rates in older patients, antibiotic

exposure, PPI use, worse initial disease• 40-60% of patients subsequently have

additional recurrences


CDI Treatment

• Vancomycin and metronidazole at 1st line therapies

• Vancomycin for severe/complicated cases• Metronidazole or vanco for 1st recurrence• Vancomycin for >=2nd recurrence• Fidaxomicin is option for recurrent cases• FMT is established for recurrent disease• Surgery


Fecal Microbiota Transplant: A History

• 4th century, Dong-jin dynasty in China, alchemist Ge Hong, Handbook of Emergency, ingest feces to treat GI problems

• Li Shizhen, Ming dynasty, 14th century, fresh/fermented/dried/infant-derived feces ("yellow soups")

• 17th century, transfaunation Italian vet practice in horses/cows

• WW II Bedouins rec German soldiers in NA to ingest warm camel feces for dysentery with good results

• Eiseman, 1st use modern clinical medicine, fecal enemas for pseudomembranous colitis with good results (Surgery, 1958)

• 1st FMT for RCDI 1983 (Schwan, Lancet, 1983)


Fecal Microbiota Transplant (FMT)

LookAt.World


Van Nood, NEJM, 2013



Rationale for considering extending isolation beyond duration of diarrhea

Clin Infect Dis 2008;46:447-50


Prevention

• Low strength of evidence: gloves, tympanic or disposable single-use thermometers

• Low strength of evidence: sporicidal disinfectants

• No data: alcohol gels versus hand-washing


Antimicrobial Stewardship

• Right drug, right dose, right time, right duration

•Stewardship of the microbiota


Dingle, Lancet ID, 2017


Definitions

• Only apply to inpatients• NHSN LabID Definition

• All positive C. difficile toxin B PCR tests + date of test + date of admission

• Positive test


Measuring CDI

“Potential cases are typically identified by a laboratory test on stool positive for C. difficile and/or its toxins. Laboratory-based reporting also utilizes positive tests to identify cases, but chart review is not performed. Rather, it is assumed that all positive tests are patients with CDI, and the date of stool collection is used as a proxy for the date of symptom onset. Comparisons between the methods of surveillance have been performed, and the 2 methods typically have good concordance in correctly categorizing CDI cases into the proper surveillance definition.”


Testing

•Surveillance Testing• Routine surveillance on all inpatients not recommended• Strength of evidence for targeted surveillance is low

•Disease Detection• Indication for testing is based on clinical criteria (fever,

leukocytosis, diarrhea, abdominal pain, sepsis, shock, toxic megacolon)

• 3 or more liquid stools in a 24 hour period• Not tested in the last 7 days• Not on stool softeners• Liquid stool = Bristol stool scale 6 or 7• Do not test for cure


Testing

• Surveillance Testing• Routine surveillance on all inpatients not recommended• Strength of evidence for targeted surveillance is low

• Disease Detection• Indication for testing is based on clinical criteria (fever, leukocytosis,

diarrhea, abdominal pain, sepsis, shock, toxic megacolon)• 3 or more liquid stools in a 24 hour period• Not tested in the last 7 days• Not on stool softeners• Liquid stool = Bristol stool scale 6 or 7

• Reality at HMC• Frequent testing on any patient with loose stools by physicians and

nurses• Only limit to testing is 1 test per 24 hours and on unformed stool

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2015 2016 2017Positive 120 229 150Negative 1127 2079 1159Indeterminate 14 24 10

1127

2079

1159

120

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500

1000

1500

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Total C.diff tests (stool only)

Indeterminate Negative PositivePresented at WSHA/ASHNHA Partnership for Patients Safe Table – November 8, 2017

2015 2016 2017Positive 120 229 150Negative 1127 2079 1159Indeterminate 14 24 10

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Total C.diff tests (stool only)

Indeterminate Negative Positive

9.6% positive

9.9% positive

11.5% positive


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26%

4%7%

22%

41%

Positive C. difficile Tests 2016Days since last laxative

no lax/≥4d

0

1

2

3


23%

3%6%

19%

49%

All C. difficile tests 2017Days since last laxatives

nolax/>4d0

1

2

3


Harborview Medical Center Approach

•Focus on identification and contact enteric precautions & hand hygiene

•Terminal cleans with bleach•Robust cleaning audits


•All rooms cleaned with bleach•RN driven testing with any concerns for disease

•UV-C for CDI terminal cleans•No change in numbers/rate….

TSICU

Longtin, JAMA Int Med, 2016Presented at WSHA/ASHNHA Partnership for Patients Safe Table – November 8, 2017

Are colonized patients the source?

Are patients with CDI colonized on admission?


TSICU



Methods: Screening for toxigenic C.difficile was conducted on all patients via rectal swab PCR within 24 hours of ICU admission. C.difficile colonized patients were placed in contact enteric precautions for the entire hospitalization and monitored for signs and symptoms of CDI. Retrospective chart review was conducted to investigate risk factors associated with development of CDI.

Results: 868 rectal swabs were collected on ICU patients from April 1, 2016 to October 31, 2016. 40 patients (5%) were found to be colonized on ICU admission and 20 (50%) went on to develop symptomatic CDI (Table 1). Risk factors for the development of CDI among C.difficilecolonized patients include enteral feeds and use of multiple antibiotics (Table 2).

Conclusions: In our study, 50% (20/40) of C.difficile colonized patients in the ICU developed CDI during their hospitalization. Asymptomatic C.difficile carriers may be a particularly vulnerable population for the development of CDI and warrants further investigation for early identification of colonized patients and strategies for infection prevention.

Review of HMC Screening Data


CDIN=20 (%)

No CDIN=20

p-value

Enteral Feeds 10 (50) 2 (10)

Review of SHEA/IDSA RECs

From the Compendium (2014) and Clinical Practice Guidelines (2010)



Testing recs

• Testing of stool on asymptomatic patients is not clinically useful, including test of cure

• Testing patients without clinically significant diarrhea will decrease the positive predictive value of a positive test for CDI

• Repeat testing during the same episode of diarrhea is of limited value and should be discouraged

• Automatic, consecutive repeat testing for C.diff will increase the number of false positive and has not been associate with better patient outcomes

• If nurse driven testing, RNs should be educated on proper patient selection for C.diff (clinically significant diarrhea in a patient without other reasons for clinically significant diarrhea)


Identifying Asymptomatic Patients

• Routine identification of asymptomatic carriers (patients or HCW) is not recommended and treatment of such patients is not effective

• Patients without s/s of CDI should not be tested• Only culture can detect colonization

• the sensitivity, specificity, PPV, NPV of other assays are unknown

• A positive toxin result in an asymptomatic patient may result in unnecessary treatment which may increase the patients risk of developing CDI in the future


Screening patients

• We have not seen a decrease in rates from screening patients and isolating colonization

• It’s impossible to know if rates would have been higher had we not implemented screening

• The only way to possibly get an idea would be to swab and not place in precautions (!)

• No evidence this is preventing transmission or CDI


Treatment of Asymptomatic Patients

• Do not place patients at high risk for CDI on prophylactic antimicrobial CDI therapy

• Do not treat or decolonize asymptomatic C.diff carriers.• Antimicrobial therapy is not effective for decolonization• May increase patient’s risk of developing CDI in the future


Prevention measures

Horizontal transfer prevention• Hand Hygiene• Contact Precautions

• Gloves have most supportive evidence

• Facilities• Single rooms/private

commode• Cleaning (sporicidal agents,

UV-C)

Prevention of disease development• Antimicrobial

stewardship• Optimize antimicrobial

use• Diagnostic stewardship• PPI stewardship• Probiotics

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In standard + contact enteric precautions

NOT in standard + contact enteric precautions

NOT in standard + contact enteric precautions

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Environment?

Antimicrobial use?

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Major themes

• Appropriate Testing• Antimicrobial Stewardship• Nutrition (Prebiotic and Probiotic use) • Environmental Cleaning• HH/Contact Precautions/Transport


Appropriate Testing

• Amount of testing has increased. 1261 tests in 2015 to 1318 tests in 2017 TD.– MD and RN driven protocols– Overall general concern for patients– Earlier detection better outcomes?

• Testing in the setting of stool softeners: Adding IT component for testing restrictions

• Utility of surveillance testing: what to do with colonized patients


Antimicrobial Stewardship

• We all are stewards of antimicrobial usage• Restriction of antimicrobial usage

– Barriers: FTE, C diff strain identification, variance in provider practice, dissemination to residents

• How to handle colonized patients• Use of prebiotic and probiotics for all

hospitalized patients/those on abx


Environmental Cleaning

• Increased use of UV-C technology– Barriers: FTE, architecture, engineering, patient

flow (time constraints) – IPC and EVS process map for comprehensive UV-C

program• Bleach protocol

– Long term effect on equipment • Axillary Areas: Cleaning protocol post

procedure/test


HH/Contact Precautions/Transport

• Soap and Water- Increased compliance with hand sanitizer?

• Contact Precautions: For CDI vs Colonized patients

• Comprehensive and consistent way to transport


Summary

• C. difficile is an opportunist that preys on dysbiotic human environments

• Diagnosis requires clinical signs/symptoms + testing

• Treatments are improving (overall)• Incidence is not (overall)• Controlling this epidemic will require new

insight into the biology of the organism and behavioral/structural interventions needed


Take Homes

• Complex organism• Our understanding of biology, transmission

and pathogenesis is woefully incomplete• Answers likely include environment +

antimicrobial stewardship + lab stewardship + better management of microbiota + hand hygiene

• Interventions dependent on setting


References

Bagdasarian, N., Rao, K. & Malani, P. N. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA 313, 398–408 (2015).

Goldberg, E. J. et al. Clostridium difficile infection: A brief update on emerging therapies. Am. J. Health. Syst. Pharm. 72, 1007–1012 (2015).

Martin, J. S. H., Monaghan, T. M. & Wilcox, M. H. Clostridium difficile infection: epidemiology, diagnosis and understanding transmission. Nat. Rev. Gastroenterol. Hepatol. 13, 206–216 (2016).

"The analyses upon which this publication is based were performed under Contract Number HHSM-500-2016-00077C entitled, "Hospital Improvement

Innovation Network," sponsored by the Centers for Medicare & Medicaid Services, Department of Health and Human Services."

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john lynch, md, mph harborview medical center university ...john lynch, md, mph. harborview medical...

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