Clostridium difficile Infection

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Clostridium difficile Infection Glenn H. Lytle, MD Medical Director Oklahoma Foundation for Medical Quality. Clostridium difficile Infection. At the end of this presentation, attendees will: Better understand the epidemiology and impact of C. difficile infections
Clostridium difficileInfectionGlenn H. Lytle, MDMedical DirectorOklahoma Foundation for Medical QualityClostridium difficile Infection
  • At the end of this presentation, attendees will:
  • Better understand the epidemiology and impact of C. difficile infections
  • Understand evidence based principles which can help to curtail and treat this infection
  • Formulate ways to improve the compliance of healthcare organizations in utilizing infection-control principles
  • Clostridium difficile Infection
  • Healthcare-Associated Infections (HAIs)
  • 2.4 million patients in U.S. hospitals annually
  • Cost of $ 35.7 billion to $ 45 billion.
  • All HAIs are declining exceptClostridium difficile
  • Up 300% over last decade
  • C. difficile - remains at high levels and has surpassed MRSA as the most common HAIs.
  • WHY?
  • From: “Lesser-known c.diff a bigger hospital threat than MRSA? USA Today. March 22,2010.
  • Clostridium difficile Infection
  • Clostridium difficile Infection (CDI) is:
  • Common – 450,000-700,000 cases in U.S. per year
  • 350,000 hospitalizations per year
  • 14,000 deaths per year in U.S.
  • Often hospital acquired – but 75% first diagnosed in
  • nursing homes or from patients recently discharged
  • At risk: >50% of cases and >90% of deaths are >65 years
  • Also at risk those who have taken antibiotics; or received
  • medical care
  • From: http://www.cdc.gov/HAI/organisms/cdiff/Cdiff_infect.html
  • http://www.cdc.gov/vitalsigns
  • http://www.cloroxprofessional.com Clostridium Difficile Prevention Guide
  • Clostridium difficile Infection
  • Some striking facts about CDI:
  • Easily transmitted by fecal-to-oral route
  • 13 out of every 1000 inpatients are either infected or
  • colonized with C.difficile
  • So on any given day, more than 7,000 inpatients
  • in U.S. hospitals have C.difficile
  • Some annual cost estimates of up to $ One billion dollars
  • From: APIC National Prevalence Study of Clostridium difficile in US Healthcare Facilities at:http://www.infectioncontroltoday.com/
  • Clostridium difficile Infection
  • What is C. difficile?
  • Clostridium difficile (C. difficile) - gram-positive, anaerobic, spore-forming bacterium – first described in 1935 - related to bacterium that causes tetanus and botulism - first thought not to be a pathogen (found in fecal flora of healthy newborns) - named difficile because hard to grow in culture.
  • The role of C. difficile in antibiotic-associated diarrhea and pseudomembranous colitis was first established in 1978.
  • From: http://emedicine.medscape.com/article/186458-overview
  • Clostridium difficile Infection
  • What is C. difficile?
  • C. difficile has two forms:
  • active- infectious form that cannot survive in the environment for prolonged periods, and
  • nonactive- "noninfectious" form, a spore, that can survive in the environment for prolonged periods and, when ingested, can then be transformed into the active, infectious form
  • From: http://www.medicinenet.com/clostridium_difficile_colitis/article.htm
  • Clostridium difficile Infection
  • What is C. difficile?
  • C. difficile colitis results from a disturbance or reduction of the normal bacterial flora of the colon – often because of the use of antibiotics – allowing pathogenic strains of C. difficile to multiply.
  • Pathogenic strainsof C. difficile produce two distinct toxins:
  • Toxin A – an enterotoxin
  • Toxin B – a cytotoxin
  • Both toxins play a role in C. difficile colitis.
  • Clostridium difficile Infection
  • How C.difficile spreads
  • By healthcare providers
  • Clostridium difficile Infection
  • Reservoirs of C.difficile
  • By patient care items and items in room
  • Clostridium difficile Infection
  • How does C. difficile become a problem?
  • C. difficile spores may lie dormant inside the colon until a person takes an antibiotic. The antibiotic disrupts the normal colonic bacterial flora allowing
  • C. difficile to proliferate and transform into its active, infectious and toxin-producing form. The bacteria produces toxins (chemicals) causing inflammation and damage to the colon – causing diarrhea
  • From: http://www.medicinenet.com/clostridium_difficile_colitis/article.htm
  • Clostridium difficile Infection
  • CDI: Pathogenesis
  • Ingestionof spores transmitted from other patients via the hands of healthcare personnel and/or from environmentAltered intestinal flora (due to antimicrobial use) allows proliferation of C. difficile in colonToxin A & B productionleads to colon damage Clostridium difficile Infection
  • How does a C. difficile infection present ?
  • Majority present with diarrhea – sometimes bloody. Severity can vary. In severe cases, the toxins kill the tissue of the inner lining of the colon, and the tissue falls off, giving the appearance of a white, membranous patch covering the inner lining of the colon. This severe form of C. difficile colitis is called pseudomembranous colitis. Not everybody infected with C. difficile develops symptoms, some are just carriers (infected but no symptoms).
  • From: http://www.medicinenet.com/clostridium_difficile_colitis/article.htm
  • Clostridium difficile Infection
  • Pseudomembranous Colitis
  • almost always due to C. difficile
  • signs and symptoms
  • diarrhea – often watery and sometimes bloody
  • abdominal cramps and pain
  • pus or mucus in stool
  • nausea
  • dehydration
  • Clostridium difficile Infection
  • Pseudomembranous Colitis
  • Complications
  • hypokalemia (low potassium)
  • dehydration
  • kidney failure
  • perforated colon
  • toxic megacolon
  • Clostridium difficile Infection
  • Why are C. difficile infections (CDI) increasing?
  • One very important reason:
  • Wide-spread use of antibiotics
  • This brings up the concept of “Antibiotic Stewardship”
  • This is basically aimed at making sure that:
  • antibiotics are used only when necessary,
  • for only as long as necessary, and only when
  • absolutely needed; and that when used, only the most appropriate antibiotic is used.
  • Clostridium difficile InfectionConcepts of Antibiotic Stewardship
  • The primary goal of antimicrobial stewardship is to optimize clinical outcomes while minimizing non-intended consequences of antimicrobial use, including toxicity, the selection of pathogenic organisms (such as
  • Clostridium difficile), and the emergence of resistance.
  • Effective antimicrobial stewardship programs can be financially self-supporting and improve patient care.
  • Dellit TH, et al. Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship. Clin Infect Dis. 2007; 44:159-77
  • Clostridium difficile InfectionANTIMICROBIAL STEWARDSHIPClostridium difficile Infection
  • Concepts of Antibiotic Stewardship
  • prospective audit with intervention and feedback
  • formulary restriction and preauthorization for specific agents
  • use of guidelines and clinical pathways
  • avoidance of use of antibiotics for:
  • nonbacterial syndromes
  • asymptomatic bacteriuria
  • colonization
  • shortened duration of antibiotic therapy
  • combination therapy
  • antimicrobial cycling and scheduled antimicrobial switch
  • Adopted from Wlodaver, W. & Nay, C. Antibiotic Stewardship. Infect Dis Clin Pract 2012; 20: 12-17.
  • Dellit TH, et al. Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship. Clin Infect Dis. 2007; 44:159-77
  • Clostridium difficile Infection
  • Why else are CDI’s increasing?
  • Possible other reasons include:
  • Increasing community-acquired cases (1)
  • Association between proton-pump inhibitors (PPIs)
  • and CDI - studies show a higher rate with PPI use, and an even greater risk when combined with antibiotics.(2,3)
  • More sensitive tests for C.difficile (depending on tests
  • used, comparing hospital data may be inaccurate)
  • 1. Leffler & Lamont. Not so nosocomial anymore: The growing threat of community-acquired C.difficile.
  • Am J Gastroenterol 2012; 107:96-98
  • 2. Kwok, et al. Risk of C.difficile infection with acid suppressing drugs and antibiotics: Meta-analysis. Am J Gastroenterol, 24 April 2012
  • 3. PPI therapy tied to C.difficile diarrhea in meta-analysis. Medscape article, 6/29/2012 at: http://www.medscape.org/viewarticle/766668_print
  • Clostridium difficile Infection
  • Why else are CDI’s increasing?
  • emergence of more virulent strains (BI/NAP1/027) (in Quebec outbreak, 80% due to this hypervirulent strain) 1
  • increased incidence in children
  • 12 times higher incidence in period 2004-2009
  • when compared to 1991-1997
  • 75% were “community-acquired” 2
  • Khanna S and Pardi DS. The growing incidence and severity of Clostridium difficile infection in inpatient and outpatient settings.Expert Rev Gastroenterol Hepatol. 2010;4(4):409-416
  • 2. Khanna S. Mayo Clinic Study posted May 23, 2012 by briankilen at: http://newsblog.mayoclinic.org/2012/05/23
  • Clostridium difficile Infection
  • Why else are CDI’s increasing?
  • Maybe because different data is being obtained
  • Hospital discharge diagnosis vs laboratory detection results
  • Clostridium difficile Infection
  • Reporting CDIs
  • Beginning with 1/1/2013 discharges one of the CMS Inpatient measures proposed will be to report
  • CDIs – this will occur via the National Healthcare Safety Network (NHSN) tool
  • In anticipation of this, OFMQ has started to work especially with hospitals that had a CDI rate in 2011 that exceeded 6 per 10,000 patient days
  • Clostridium difficile Infection
  • Reporting CDIs
  • Prevention Targets
  • Case Rate per 10,000 patient-days in NHSN:
  • National 5-year Prevention Target:
  • 30% reduction
  • Because the baseline infection data is minimal,
  • data for ICD-9-CM coded C. difficile hospital discharges is also tracked with same goal
  • National 5-year prevention target:
  • 30% reduction
  • Clostridium difficile Infection
  • How are CDIs detected?
  • TestSensitivity (%)Specificity (%) Advantages/Disadvantages
  • Cytotoxin assay 80-90 99-100 considered as gold standard
  • highly sensitive and specific; Takes 24-48 hr to complete;
  • requires tissue culture facility;
  • costly; detects only toxin B
  • ELISA toxin test 65-85 95-100 Fast (2-6 hr), easy to perform, high
  • specificity.
  • Not as sensitive as cytotoxin assay
  • Stool culture 90-100 98-100 Allows strain typing in epidemics
  • Takes 2-5 days to complete;
  • labor intensive;
  • not specific for toxin-producing bacteria
  • Clostridium difficile Infection
  • How are CDIs detected? (continued)
  • TestSensitivity (%)Specificity (%) Advantages/Disadvantages
  • Latex agglutination assay Fast, inexpensive, easy to perform
  • for glutamate 58-68 80-96 Poor sensitivity and specificity
  • dehydrogenase requires confirmatory test
  • PCR assay 92-97 100 Excellent sensitivity and specificity
  • toxin gene detection Expensive
  • Commercial assays recently became available
  • Endoscopy 51 ~100 Diagnostic of pseudomembranous
  • colitis; can be used without need to collect stool sample; Costly;
  • invasive test; risk of perforation
  • Adapted from : http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectious-disease/clostridium-difficile-infection/#s0030
  • Clostridium difficile Infection
  • How are CDIs detected? (continued)
  • Limited view; needs Full view; best with
  • limited prep full prep Both can be dangerous –
  • possible perforation
  • Clostridium difficile Infection
  • How are C. difficile infections (CDI) prevented?
  • Few randomized controls, but greatest evidence for prevention with:
  • Antimicrobial stewardship
  • Glove use
  • Disposable patient care items (i.e.: thermometers)
  • Probiotics – when given with antibiotics, seem to decrease antibiotic-linked diarrhea risk
  • Environmental disinfection and “soap and water”
  • hand washing is critical (hand sanitizer does not work)
  • Clostridium difficile Infection
  • How are C. difficile infections (CDI) prevented?
  • Have a Checklist for Isolation Room Cleaning Use a very detailed Protocol
  • Curtains, carpets, bed rails can hide spores easily
  • Clostridium difficile Infection
  • CDC Recommendations for Clinicians:
  • 6 Steps to Prevention
  • Prescribe and use antibiotics carefully. About 50% of all antibiotics given may not be needed, increasing the risk of C. difficile infections.
  • Test for C. difficile when patients have diarrhea (even if not bloody) while on antibiotics or within several months of taking them.
  • Isolate patients with C. difficile immediately.
  • Clostridium difficile Infection
  • CDC Recommendations for Clinicians:
  • 6 Steps to Prevention (continued)
  • Wear gloves and gowns when treating patients with C. difficile, even during short visits. Hand sanitizer does not kill C. difficile, and hand washing may not be sufficient.
  • Clean all room surfaces with bleach or another EPA-approved, spore-killing disinfectant after a patient with C. difficile has been treated there.
  • Clostridium difficile Infection
  • CDC Recommendations for Clinicians:
  • 6 Steps to Prevention (continued)
  • When a patient transfers, notify the new facility in advance if the patient has a C. difficile infection.
  • (This has led to problems where some facilities have wanted a retest before transfer – but retests may be positive for two months after successful treatment, so this practice of retests is not recommended.)
  • From: http://www.cdc.gov/HAI/organisms/cdiff/Cdiff_clinicians.html
  • Clostridium difficile Infection
  • How are CDIs treated?
  • Stop current antibiotics as soon as possible
  • Metronidazole, an oral synthetic antiprotozoal and
  • antibacterial agent is often used first orally -
  • Preferred because of cost and safety –
  • 500 mg po tid or 250 mg po qid for 10-14 days.
  • Can be used IV – 500 mg IV q8h if npo
  • Side-effects: some dose-dependent peripheral
  • neuropathy; nausea; metallic taste
  • From UpToDate: Treatment of Clostridium difficile infection in adults; at www.uptodate.com
  • Clostridium difficile Infection
  • How are CDIs treated? (continued)
  • Vancomycin, a glycopeptide antibiotic, is often next
  • drug to be used; 125 mg po qid (as effective as
  • 500 mg po qid) for 10-14 days - Not effective IV
  • for C.difficile. Metronidazole and Vancomycin
  • both have about a 20-30% recurrence rate.
  • Repeat stool assays are NOT warranted post- treatment; since 50% of symptom-free patients’
  • stool tests will be positive for up to 6-8 weeks
  • From UpToDate: Treatment of Clostridium difficile infection in adults; at www.uptodate.com
  • Clostridium difficile Infection
  • How are CDIs treated? (continued)
  • Recurrent disease - Most treated with Vancomycin –
  • administered in a ‘pulse tapered’ fashion
  • pulse – administering drug every few days
  • tapered – decrease in dose over time
  • Fidaxomicin
  • A macrocyclic antibiotic with a narrow spectrum;
  • FDA approved in 2011; 200 mg po bid for 10 days;
  • appears to have fewer complications and recurrences.
  • From UpToDate: Treatment of Clostridium difficile infection in adults; at www.uptodate.com
  • Clostridium difficile Infection
  • How are CDIs treated? (continued)
  • Supportive treatment (fluids, etc)
  • For severe disease, may use both high dose oral vancomycin (500 mg po qid) and
  • IV metronidazole (500 mg IV q8h)
  • For patients with profound ileus, may use
  • intracolonic vancomycin
  • Surgery – for complications - peritonitis, severe ileus, or toxic megacolon – especially with hypervirulent strain or immunocompromised patient
  • From UpToDate: Treatment of Clostridium difficile infection in adults; at www.uptodate.com
  • Clostridium difficile Infection
  • How are CDIs treated? (continued)
  • innovative therapy – fecal transplants –
  • called Fecal Microbiota Therapy (FMT) - first discussed in the literature in the late 1950’s. This therapy basically reintroduces bacterial flora into colon by placing someone else’s stool into patient’s intestine - can be delivered by colonoscopy or enema –stool is first screened for hepatitis, HIV, syphilis and other diseases.
  • 90-98% success in recurrent and resistant cases
  • Abigal Zuger, MD: Found at: http://www.medscape.com.viewarticle/761648_print
  • Clostridium difficile Infection
  • I am now going to show you a ‘youtube’ video about
  • Fecal Microbiota Therapy
  • As a surgeon for thirty years and after having performed some 300 colonoscopies per year – I think the video is very informative – however – my wife, who has been a nurse for twenty-five years, thought it was gross – especially for over the noon hour - So – I am giving you a warning
  • Clostridium difficile InfectionClostridium difficile Infection
  • Is this ‘the perfect cure’?
  • In one study of Fecal Microbiota Therapy (FMT) -
  • Patients’ mean age of 73
  • Most had three to six courses of failed antibiotics
  • Three months following fecal transplantation,
  • 66 of 70 reported complete resolution of symptoms
  • The other four had died – 95% success
  • So it seems to work in all but the incurable cases.
  • This is a great result, but saying it works “in all but the incurable cases” reminds me of a story about Galen
  • Abigal Zuger, MD: Found at: http://www.medscape.com.viewarticle/761648_print
  • Clostridium difficile Infection
  • Galen
  • Galen was a second century physician of some importance – in historical perspective, ranking up there with Hippocrates.
  • Clostridium difficile Infection
  • Galen came up with a treatment for a serious and deadly infection – he praised his own result by saying:
  • All who drink of this remedy
  • recover in a short time,
  • except those whom it does not help,
  • who all die.
  • Therefore, it is obvious
  • that it fails only in incurable cases
  • Found at: http://www.truth-in-quotes.com/humor/perfect-cure/
  • Questions?Glenn H. Lytle, MDMedical Director, OFMQglytle@ofmq.comElanor Wallis, RN, BSNewallis@ofmq.comThis material was prepared by Oklahoma Foundation for medical Quality, the Medicare Quality Improvement Organization for Oklahoma, under contract with the Centers for Medicare & Medicaid Services (CMS), an agency of the U.S. Department of Health and Human Services. The contents presented do not necessarily reflect CMS policy. 10C7HQR-1278-OK-0911
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