Update on C. difficile prevention and management Nimalie D. Stone, MD,MS Ambulatory and Long-term Care Team Division of Healthcare Quality Promotion Georgia GAPNA Conference March 2, 2013 National Center for Emerging and Zoonotic Infectious Diseases Division of Healthcare Quality Promotion

Clostridium difficile infections (CDI) • Anaerobic spore-forming bacillus – Gram stain positive rods under microscope

• Causes severe infections including: pseudomembranous colitis, toxic megacolon, sepsis, and death • Fecal-oral transmission through contaminated environment and hands of healthcare personnel • Antimicrobial exposure is major risk factor for disease

Healthy colon

Pseudomembranous colitis

Background: Pathogenesis of CDI 1. Ingestion of spores transmitted from other patients via the hands of healthcare personnel and environment

3. Altered lower intestine flora (due to antimicrobial use) allows proliferation of 4. Toxin A & B Production C. difficile in colon leads to colon damage +/- pseudomembrane

2. Spores change (germination) into growing (vegetative) form

Sunenshine et al. Cleve Clin J Med. 2006;73:187-97.

Risk Factors for C. difficile Infection • • • • • • •

Antimicrobial exposure Acquisition of C. difficile Gastric acid suppression Advanced age Underlying illness Immunosuppression Tube feeds

Main modifiable risk factors

Disproportionate impact of CDI in the elderly

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

Current Epidemic Strain of C. difficile Referred to as BI/NAP1/027, toxinotype III  Historically uncommon 

Epidemic since 2000  Epidemic behavior coincident with increased resistance to fluoroquinolones 

Carries extra toxin known as binary toxin  More virulent: mechanisms? 

Increased toxin A and B production  Polymorphisms in binding domain of toxin B McDonald LC et al. N Engl J Med. 2005;353:2433.  Increased sporulation? Warny M et al. Lancet. 2005;366:1079. 

Stabler et al. J Med Micro. 2008;57:771–775. Akerlund T et al. J Clin Microbiol. 2008;46:1530–33

Nursing homes account for a substantial burden of healthcare related CDI  

94% health care related 75% of these outside hospitals  Nursing home residents  Patients in community • Outpatient exposures only • Recent inpatient exposure

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Post-discharge CDI common  Most potent antibiotics used in hospitals  Lasting effect on patients CDC, MMWR;2012;61: 1-6

Changing nursing home resident population 

In 2009, ~3.3 million residents received care in the 15,884 nursing homes in US  Primary source of admission are hospitals

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From 2000 to 2009  10% increase in the number of residents entering NHs;  15% decrease in nursing home beds/1,000 residents in US  Increasing proportion of individuals 60; Tm >38.3; Serum albumin 60 days) may have improved response to fecal transplant

Longer term follow-up among 77 patients (median time 17 months from therapy  91% primary cure; 98% secondary cure after 1 relapse  97% reported would undergo fecal transplant again Gough E et al. Clinical Infectious Diseases 2011;53(10):994–1002 Sofi AA et al. Scand J Gastroenterology. 2013; 48: 266–273 Brandt LJ et al. Am J Gastroenterol 2012; 107:1079–1087

Case study on care transitions 

A LTC resident was transferred to a local ED with worsening lower extremity swelling and shortness of breath 

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PMHx included h/x CAD, DM with neuropathy, BPH

Diagnosed with congestive heart failure admitted to ICU for cardiac monitoring and diuresis A urinary catheter was placed at the time of admission and a specimen was sent for UA/culture in ED. 

Based on the UA, the patient was started on antibiotics

Case study (continued) 

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7 days later, after treatment for CHF and the positive UA the patient was discharged back to the LTC facility with the catheter in place. Prior to removing the urinary catheter a repeat culture was sent which grew VRE 

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A second course of antibiotics was initiated

Two weeks later the resident developed diarrhea and fever 

Stool sample was positive C. Diff toxin test.

Issues Raised by this Case Study  

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How are providers utilizing laboratory testing for diagnosis? How are providers communicating information about devices, antibiotic exposures and other risk factors at time of transfer? How are providers using antibiotics in this shared population? 

Which facility is accountable for the complications of antibiotic use?

Association of specific antibiotic exposures with risk of CDI  Large

cohort of patients in a nonoutbreak setting  Fluoroquinolone antibiotics have been associated with CDI from NAP1 strain  Longer antibiotic exposure carries higher risk

Ways antibiotics can be misused

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Given when they are not needed Continued when they are no longer necessary Given at the wrong dose Broad spectrum agents are used to treat very susceptible bacteria • The wrong antibiotic is given to treat an infection

http://www.cdc.gov/getsmart/healthcare/inpatient-stewardship.html#Facts

Antimicrobial use in NHs 

Antimicrobials are the most frequently prescribed drug class in nursing homes 

Comprise ~40% of all prescriptions

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50-70% of residents will receive a systemic antimicrobial during the course of a year

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25-75% of antimicrobial use may be inappropriate

Benoit et al. JAGS 2008; 56: 2039-2044 Nicolle LE et al. ICHE 2000; 21:537-545

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Antimicrobial use in NHs varies across facilities 

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Pooled mean 4.8 courses/1,000 resident days, range 0.4-23.5)

Primary indications are urinary and respiratory tract infections Fluoroquinolones are the most commonly used 

38% of all prescriptions

Benoit et al. JAGS 2008; 56: 2039-2044

Antibiotic Stewardship Careful antibiotic use is a critical component in the control of C. difficile  Know the frequency/indications for antibiotic use by medical providers in your facility 

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Apply criteria to assess utilization in a standard way

Develop standard protocols for assessing residents who are suspected to have new infections Standardize information provided during communication between nursing staff and clinicians  Ensure documentation of signs/symptoms is complete  Reassess need for antibiotics once further data is available 

Final thoughts Preventing and managing C. difficile infections is a serious challenge in the older adult and long-term care population  Movement of patients between healthcare and the community increases exposure to risk factors for CDI and impacts where illness is diagnosed  Basic infection prevention measures to prevent spread and acquisition of C. diff is critically important in long-term care  Improving antibiotic use in all healthcare settings is a major key to preventing primary and recurrent CDI 

Thank you!! Email: [email protected] with questions/comments For more information please contact Centers for Disease Control and Prevention 1600 Clifton Road NE, Atlanta, GA 30333 Telephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348 E-mail: [email protected] Web: www.cdc.gov The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

National Center for Emerging and Zoonotic Infectious Diseases Division of Healthcare Quality Promotion