Clostridium Management in Long-Term Care. Spring 2011 Joint Provider/Surveyor Training Teri Lee Dyke, RN, MSN, CIC. Clostridium difficile Infection ( C. diff , CDI, C. difficile & CDAD ). Two Case Reports * [Case 1]. Case 1.
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Clostridium Management in Long-Term Care Spring 2011 Joint Provider/Surveyor Training Teri Lee Dyke, RN, MSN, CIC
Two Case Reports *[Case 1] • Case 1 *MMWR 2005;54:1201-5Severe CDAD in populations previously at low risk- four states, 2005
Two Case Reports *[Case 2] • Case 1 *MMWR 2005;54:1201-5Severe CDAD in populations previously at low risk- four states, 2005
Why C. difficile is interesting • It is a bacterial infection in which antibiotics cause (or at least contribute to) the disease • It is one of the only anaerobic organisms that can be a nosocomial pathogen • Its mechanism of pathogenesis is almost completely toxin production; it does not invade the tissues • It is the only nosocomial pathogen that forms endospores that are nearly impossible to kill • The most effective treatment for the disease may be to expose the patient to more bacteria
Outline • Clostridium Difficile the disease • Epidemiology • Infection Prevention/Mitigation • Strategies for Management in LTC • Resources
Microbiology • Description • Gram positive spore-forming anaerobic bacteria • Natural habitat • GI tract of mammals • Identification • Not normally cultured from stool; difficult to grow
Clostridium difficile • Anaerobic spore-forming bacillus • Clostridium difficile-associated disease or diarrhea (CDAD) • 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 • Acquisition and growth of C. difficile • Suppression of normal flora of the colon • Clindamycin, penicillins, and cephalosporins Healthy colon Pseudo-membranous 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 C. difficile in colon 4. Toxin A & B Production leads to colon damage +/- pseudomembrane 2. Germination into growing (vegetative) form Sunenshine et al. Cleve Clin J Med. 2006;73:187-97.
Background: EpidemiologyRisk Factors Antimicrobial exposure Acquisition of C. difficile Advanced age Underlying illness Immunosuppression Tube feeds ? Gastric acid suppression Main modifiable risk factors
Modes of Transmission • Fecal-oral • Food • Fomite (contaminated object) • Person-to-person • Taking care of an ill individual • Fomite (contaminated object) • Inpatient healthcare setting • Previous antibiotic exposure
Symptoms of CDAD • Watery diarrhea • Loss of appetite • Fever • Nausea • Abdominal pain and cramping
Colonization No clinical symptoms More common than disease presence Patient will test positive for Clostridium difficile and/or its toxin Infection Watery diarrhea Abdominal pain Fever Nausea/Vomiting Patient tests positive for Clostridium difficile and/or its toxin Colonization vs. Infection
Laboratory Testing • Stool culture • Most sensitive ( ↑ false-positives) • Labor intensive • Results in 48-96 hours • Antigen detection • Rapid tests ( < 1 hour) • Antigen detection by latex agglutination or immunochromatographicassays • Must be combined with toxin testing to verify diagnosis
Laboratory Testing continued.. • Toxin testing* • Enzyme immunoassay detects toxin A, toxin B or both • Same-day test results • Less sensitive than tissue culture cytotoxicity assay • Tissue culture cytotoxicity assay • detect toxin B only • Requires technical expertise • Costly • 24-28 hours results • Provides specific and sensitive results for c. difficile * Toxin is very unstable and degrades at room temperature such that toxin may be undetectable within 2 hours. False-negative test results may result from not conducting immediate testing or not properly refrigerating specimen
Detection of C. difficile in stool • Culture; too difficult; the organism is fastidious, takes too long • Cell-associated antigen test; fast, but doesn’t distinguish between toxin-producers and harmless strains
Detection of C. difficile in stool • Toxin antigen tests; fast, but less sensitive, can get toxin A or A+B tests * • PCR; not commercially available, not a toxin test • Cytotoxicity test; the most sensitive, specific and cost-effective • One specimen is enough, don’t need 3 • Toxin is very unstable and degrades at room temperature such that toxin may be • undetectable within 2 hours. False-negative test results may result from • not conducting immediate testing or not properly refrigerating specimen
New strain C. difficile • Standard laboratory tests will not distinguish the new from conventional strains, although all new strains to date were positive for Toxins A and B • Distinguished by clinical presentation • Can do PCR for the binary toxin and/or for the deletion in the repressor gene • Most are also fluoroquinolone-resistant, but that is not specific for this strain • Strains can be typed by pulse-field gel electrophoresis, and the new strain shows up as a single clone
CDAD Treatment • Discontinue the offending antibiotic • 23% of the patients disease will resolve within 2-3 days • Standard initial treatment of toxin-positive patients • Metronidazole 500 mg three times per day for 10-14 days • No resistance, MIC is 0.25-1, stool level is 10 • Clinical response of about 95%, relapse of 5-15% • Alternative • Vancomycin 125 mg four times per day (relapse 15-30%) • Bacitracin 25,000 units four times per day • Cholestyramine 4 grams three times per day for 10 days • For relapse • Repeat metronidazole plus rifampin 300 mg twice per day for 10 days • If that fails, go to an alternative • Replace fluid and electrolytes • Avoid anti-peristaltic agents (lomotil, opiates) • Relapse rate 5-15%
American College of Gastroenterology and SHEA Guidelines • Discontinue the offending antibiotic or change it • Replace fluids and electrolytes • Avoid antiperistaltic agents • If those fail, try one course of metronidazole (Flagyl) • Do not treat asymptomatic patients • Retreat relapses once with the same regimen • Avoid vancomycin if possible
Background: Impact Hospital-acquired, hospital-onset: 165,000 cases, $1.3 billion in excess costs, and 9,000 deaths annually Hospital-acquired, post-discharge (up to 4 weeks): 50,000 cases, $0.3 billion in excess costs, and 3,000 deaths annually Nursing home-onset: 263,000 cases, $2.2 billion in excess costs, and 16,500 deaths annually Campbell et al. Infect Control Hosp Epidemiol. 2009:30:523-33. Dubberke et al. Emerg Infect Dis. 2008;14:1031-8. Dubberke et al. Clin Infect Dis. 2008;46:497-504. Elixhauser et al. HCUP Statistical Brief #50. 2008.
Background: ImpactAge-Adjusted Death Rate* for Enterocolitis Due to C. difficile, 1999–2006 2.5 Male Female 2.0 White Black Entire US population 1.5 Rate 1.0 0.5 0 1999 2000 2001 2002 2003 2004 2005 2006 Year *Per 100,000 US standard population Heron et al. Natl Vital Stat Rep 2009;57(14). Available at http://www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_14.pdf
Challenges • Emergence of a new epidemic strain • Toxinotype III or “BI” by REA • Distinct from “J” strain of 1989-19921 • Binary toxin as a possible virulence factor • In addition to toxins A and B containing • 18 bp deletion in tcdC gene • Could lead to increased toxin production (18-fold for toxin A, 23-fold for toxin B) observed by Warny et al.2 • Increased resistance to fluoroquinolones • Appears responsible for increase in cases • May be responsible for increase in disease severity • Johnson S, et al. N Engl J Med. 1999;341:1645-1651. • Warny M, et al. Lancet. 2005;366:1079-1084.
CDAD Surveillance Data • Not reportable • NNIS data up to 1990s • Started in Northeast, now spread to Midwest and South
Annual CDAD Rates, Hospitals with >500 Beds, Intensive Care Unit Surveillance Component, NNIS From Archibald LK, et al. J Infect Dis. 2004;189:1585–158.
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
Rates of US Short-Stay Hospital Discharges with C. difficile Listed as Any Diagnosis by Region From McDonald LC, et al. Emerg Infect Dis. 2006;12(3):409-15
2 1 2 1 1 1 Acute Care Hospitals with CDAD Outbreaks* Between 2001-2004 *Detected by increases in the number of positive routine clinical laboratory tests for C. difficile. Data from McDonald LC, et al. N Engl J Med. 2005;353:2433-2441.
States with the Epidemic Strain of C. difficile Confirmed by CDC and Hines VA labs (N=27),Updated 4/3/2007 DC HI PR AK
Michigan Data • Death certificates with C. difficile • Underlying cause • Any mention
Death Certificates in Michigan Clostridium Difficile 1999-2005 any mention of C. difficile
Michigan Source: 2005 death file, data records and health data development section MDCH
Michigan Source: 2005 death file, data records and health data development section MDCH
Increasing Severity and Costs of CDAD • Boston, 1998¹ • Low attributable mortality • Average 3,600 excess cost per case • Average of 3.6 extra hospital days • Pittsburgh, 20002 • Life-threatening disease from 1.6% to 3.2% • 2000-2001: 26 colectomies and 18 deaths • Quebec, 2004 • 30-day attributable mortality 6.9% • 12-month attributable mortality 16.7% • Average of 10.7 extra hospital days • Dallal RM, et al. Ann Surg. 2002;235:363-372. • Muto C, et al. Infect Control HospEpid. 2005 • Pepin J, et al. CMAJ. 2005
Changing epidemiology • Old model of disease; the patient carried the organism into the hospital with them, antibiotics during hospitalization induce toxin production and disease • This hypothesis was tested by culture of hospitalized patients on admission and then weekly • The model proved false
Changing epidemiology • New model for C. difficile disease; the organism is not usually endogenous, antibiotics during hospitalization predispose the patient to colonization, the organism is then acquired in the hospital and causes disease; a nosocomial infection • In fact, one study showed that colonization with C. difficile prior to hospitalization was protective against C. difficile disease after hospitalization • Neonates often carry the organism but lack the receptors for the toxin, do not get disease
Epidemiology • Asymptomatic colonization • Community surveys show that 1-3% of the population normally carries the organism asymptomatically • Among hospitalized patients, 20% carry it • CDAD was associated with elderly and long LOS inpatients and nursing homes • Now increasing in non-patients as a community-acquired disease, in children and young adults, with little antibiotic pre-exposure • CDAD was associated with use of clindamycin and cephalosporins
Epidemiology; inciting agents and risk factors • Almost all antibiotics and many antineoplastic agents have caused disease • Most commonly cited: beta-lactams, clindamycin, fluoroquinolones • Less commonly cited; Timentin, tetracyclines, SXT, aminoglycosides • Risk factors: • Advanced age, underlying illness, immunologic susceptibility (IgG, not cellular)
Recent studies • Pepin, et al. 2005. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea; a cohort study during an epidemic in Quebec (CID 41:1254-1260) • Since 2002, 30 hospitals, 7000 cases, rate of 15/10,000 patient days, increase in severe disease • Quinolone use had an odds ratio of 3.44, 2nd generation cephalosporins 1.89 • The drug made a difference; gatifloxacin was worst, levofloxacin was best
Recent studies • Loo, et al. 2005. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. NEJM 353:2442-2449. • Studied 12 Quebec hospitals, 1719 patients, 22.5/1000 admissions • Attributable mortality was 6.9% • Of 157 isolates from 9 hospitals, 129 were identical • All isolates were susceptible to metronidazole and vancomycin • Aminoglycosides and penicillins were protective (odds ratio), cephalosporins, fluoroquinolones and clindamycin were associated with disease
Recent studies • McDonald, et al. 2005. An epidemic, toxin gene-variant strain of Clostridium difficile. NEJM 353:2433-2442 • Collected 187 strains from 8 hospitals in Georgia, Illinois, Maine, New Jersey, Oregon and Pennsylvania in 2003 • Typed by restriction endonuclease typing, PFGE, toxin typing • Compared with a library of older C. difficile strains • Most of the new strains were identical, and were different from all strains collected before 2001 • The new toxin genes and fluoroquinolone resistance are new
Prevention Strategies: Core Contact Precautions for duration of diarrhea Hand hygiene in compliance with CDC/WHO Cleaning and disinfection of equipment and environment Laboratory-based alert system for immediate notification of positive test results Educate about CDI: HCP, housekeeping, administration, patients, families http://www.cdc.gov/ncidod/dhqp/id_CdiffFAQ_HCP.html Dubberke et al. Infect Control Hosp Epidemiol 2008;29:S81-92.
Prevention Strategies: Supplemental Extend use of Contact Precautions beyond duration of diarrhea (e.g., 48 hours)* Presumptive isolation for symptomatic patients pending confirmation of CDI Evaluate and optimize testing for CDI Implement soap and water for hand hygiene before exiting room of a patient with CDI Implement universal glove use on units with high CDI rates* Use sodium hypochlorite (bleach) – containing agents for environmental cleaning Implement an antimicrobial stewardship program * Not included in CDC/HICPAC 2007 Guideline for Isolation Precautions
Supplemental Prevention Strategies: Consider presumptive isolation for patients with > 3 unformed stools within 24 hours Patients with CDI may contaminate environment and hands of healthcare personnel pending results of diagnostic testing CDI responsible for only ~30-40% of hospital-onset diarrhea However, CDI more likely among patients with >3 unformed (i.e. taking the shape of a container) stools within 24 hours Send specimen for testing and presumptively isolate patient pending results Positive predictive value of testing will also be optimized if focused on patients with >3 unformed stools within 24 hours Exception: patient with possible recurrent CDI (isolate and test following first unformed stool)
Supplemental Prevention Strategies: Glove Use Rationale for considering universal glove use (in addition to Contact Precautions for patients with known CDI) on units with high CDI rates Although the magnitude of their contribution is uncertain, asymptomatic carriers have a role in transmission Practical screening tests are not available There may be a role for universal glove use as a special approach to reducing transmission on units with longer lengths of stay and high endemic CDI rates Focus enhanced environmental cleaning strategies and avoid shared medical equipment on such units as well
Supplemental Prevention Strategies: Environmental Cleaning Bleach can kill spores, whereas other standard disinfectants cannot Limited data suggest cleaning with bleach (1:10 dilution prepared fresh daily) reduces C. difficile transmission Two before-after intervention studies demonstrated benefit of bleach cleaning in units with high endemic CDI rates Therefore, bleach may be most effective in reducing burden where CDI is highly endemic Mayfield et al. Clin Infect Dis 2000;31:995-1000. Wilcox et al. J Hosp Infect 2003;54:109-14.
Supplemental Prevention Strategies: Environmental Cleaning Assess adequacy of cleaning before changing to new cleaning product such as bleach Ensure that environmental cleaning is adequate and high-touch surfaces are not being overlooked One study using a fluorescent environmental marker to asses cleaning showed: only 47% of high-touch surfaces in 3 hospitals were cleaned sustained improvement in cleaning of all objects, especially in previously poorly cleaned objects, following educational interventions with the environmental services staff The use of environmental markers is a promising method to improve cleaning in hospitals. Carling et al. Clin Infect Dis 2006;42:385-8.