Educational Objectives Discuss the pathophysiology of Clostridium difficile infection (CDI) as it relates to clinical disease Analyze elements which contribute.

Educational Objectives• Discuss the pathophysiology of Clostridium difficile infection

(CDI) as it relates to clinical disease

• Analyze elements which contribute to the economic burden of CDI

• Identify important risk factors for initial CDI and recurrence

• Apply therapeutic strategies for improved patient outcomes

• Implement methods to prevent CDI in high-risk patients

CDI Overview: 60 Years of Research

• Evolution of C. difficile knowledge over past 60 years– 1950: Staphylococcus enterocolitis (possibly some CDI) – 1974: “Clindamycin” colitis– 1978: C. difficile as agent of pseudomembranous colitis– 1981: Vancomycin approved by FDA for CDI– 1982: Metronidazole introduced for CDI– 1984: Enzyme immunoassays for CDI– 2000: Outbreak in Pittsburgh, PA– 2003: Outbreak in Quebec– 2005: Outbreaks throughout the US and localized in

Europe– 2011: Fidaxomicin approved by the FDA for CDI

CDI Overview

• Spore-forming, anaerobic, gram-positive bacterium

• Causes gastrointestinal infections resulting in diarrhea and colitis– Severity ranges from mild colitis

to toxic megacolon and death

• Leading cause of healthcare-associated infectious diarrhea in US

• Rivals methicillin-resistant Staphylococcus aureus (MRSA) as the most common organism to cause healthcare-associated infections in USGerding DN, et al. Infect Control Hosp Epidemiol. 1995;16:459-477.

CDC. Fact Sheet, August 2004 (updated 7/22/05).McDonald LC, et al. Emerg Infect Dis. 2006;12:409-415.

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National Estimates of US Short-Stay Hospital Discharges with C. difficile as

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Sample

Elixhauser, A. (AHRQ), and Jhung, MA. (Centers for Disease Control and Prevention). Clostridium Difficile-Associated Disease in U.S. Hospitals, 1993–2005. HCUP Statistical Brief #50. April 2008. Agency for Healthcare Research and Quality, Rockville, MD. And unpublished data http://www.hcup-us.ahrq.gov/reports/statbriefs/sb50.pdf

CDI Epidemiology• Severity of CDI appears to be increasing1-2

– Increased morbidity and mortality

• Severe infection in “low-risk” populations1-3

• Emergence of novel, hypervirulent strain (BI/NAP1/027) now reported across the US, Canada, and Europe– Increased toxin production and sporulation may

contribute to severe and widespread disease4,5

– Highly resistant to fluoroquinolones1. McDonald LC, et al. Emerg Infect Dis. 2006;12(3):409-415.2. Loo VG, et al. N Engl J Med. 2005;353:2442-2449.3. Kuijper EJ, et al. Euro Surveill. 2007;12(6):E1-E2.4. Tucker ME. http://www.ehospitalistnews.com/news/infectious-diseases/single-article/ic-difficilei-epidemic-still-poses-clinical- challenges/01e37c081f.html5. Merrigan M, et al. J Bacteriol. 2010;192:4904-4911.

Study Patient Population

Per-Episode Costs

Increase in Length of Stay

US Cost

Kyne 19981 -2 medical wards-40 cases

$3,669 3.6 days $1.1 billion

O’Brien 20002 -MA discharge database-3,692 cases

Primary diagnosis: $10,212

Secondary diagnosis: $13,675

3.0 days $3.2 billion

Dubberke 20033

-Nonsurgical patients-439 cases

$2,454 – $3,240

2.8 days $1.3 billion

1. Kyne L, et al. Clin Infect Dis. 2002;34:346-353.2. O’Brien JA, et al. Infect Control Hosp Epidemiol. 2007;28:1219-1227.3. Dubberke ER, et al. Clin Infect Dis. 2008;46:497-504.

Economic Burden of CDI

CDI Pathophysiology• Primary virulence factors:

– Toxin A (TcdA)– Toxin B (TcdB)

• Toxins A and B are potent cytotoxic enzymes that damage the human colonic mucosa

• Binary toxin (CDT) was previously identified in ~6% of C. difficile isolates, but is present in all isolates of the hypervirulent strain– Role is unknown but may potentiate toxicity of

TcdA and TcdB and lead to more severe disease

Denève C, et al. Int J Antimicrob Agents. 2009;33:S24-S28.

Asymptomatic C. difficile colonization

C. difficile acquisition

Antimicrobial(s)

CDIHospitalization

Current Pathogenesis Model for C. difficile Infection (CDI)

C. difficile acquisition

Acquisition of a toxigenic strain of C. difficile and failure to mount an anamnestic Toxin A IgG antibody response results in CDI.

Johnson S, Gerding DN. Clin Infect Dis. 1998;26:1027-1036.Kyne L, et al. N Engl J Med. 2000;342:390-397.

Risk Factors for Initial CDI

• Classic risk factors:– Antibiotic therapy– Advanced age– Prolonged stay in healthcare facility– High severity of illness

• Additional risk factors– Inflammatory bowel disease– Gastrointestinal surgery– Gastric acid suppression (PPIs)– Immunosuppression1. Hookman P, Barkin, JS. World J Gastroenterol. 2009;15:1554-1580.

2. APIC. Guide to the Elimination of Clostridium difficile in Healthcare Settings. November 2008. 3. Makris AT, Gelone S. J Am Med Dir Assoc. 2007;8:290-299.4. Cohen SH, et al. Infection Control and Hospital Epidemiology. 2010;31(5):431-455.5. Goodhand JR, et al. Ailment Pharmacol Ther. 2011;33:428-441.6. Aseeri M, et al. Am J Gastroenterol. 2008;103:2308-2313.7. Schaier M, et al. Nephrol Dial Transplant. 2004;19:2432-2436.

Identifying Patients at Risk for Recurrence and Poor

Outcomes• Elderly• Administration of antibiotics after initial

treatment of CDI• Prolonged hospitalization or stay in long-

term care facility (LTCF)• Defective immune response to toxin A• Gastric acid suppression

1. Johnson S. J Infect. 2009;58:403-410. 2. Hookman P, Barkin JS. World J Gastroenterol. 2009;15(13):1554-1580.3. Zilberberg M, et al. Crit Care Med. 2009;37:2583-2589.4. Garey KW, et al. J Hosp Infect. 2008;70:298-304.

CDI Recurrence by Age Group

Pépin J, et al. Clin Infect Dis. 2005;40:1591-1597.

Administration of Antibiotics

After Initial CDI Therapy• Continued use of non-C. difficile antibiotic after diagnosis of CDI associated with an odds ratio of 4.23 (P<0.001) for recurrent disease1

• Time to resolution of diarrhea was also increased for patients who received concomitant antibiotics (CA) during treatment for CDI in two Phase 3 CDI trials of fidaxomicn vs. vancomycin2

1. Garey KW, et al. J Hosp Infect. 2008;70:298-304. 2. Mullane KM, et al. Clin Infect Dis. 2011;53:440-447.

-The recurrence rate was also increased significantly by receipt of CA during or after CDI treatment in this study

Prolonged Hospitalization or Stay in LTCF

• Risk related to transmission of C. difficile spores– Primary source healthcare workers

• may carry C. difficile spores on their hands (not likely fecal carriers)

– Environmental contamination secondary source

• Up to 50% of LTCF residents and 40% of hospitalized patients have been found to be colonized with C. difficile or its toxin

1. McFarland LV, et al. N Engl J Med. 1989;320:204-210. 2. Bartlett JG, Gerding DN. Clin Infect Dis. 2008;46(Suppl 1):S12-S18. 3. Simor AE, et al. Infect Control Hosp Epidemiol. 2002;23:696-703. 4. Hookman P, Barkin JS. World J Gastroenterol. 2009;15:1554-1580.

Defective immune response to

toxin A• Generation of an antibody response to toxin A is associated with protection against symptomatic disease and asymptomatic carriage of C. difficile

• Following symptomatic infection, many individuals develop anti-toxin A and B antibodies

• Inability to acquire immunity to toxin A increases risk for recurrent disease– Individuals with recurrent CDI

mount poor anti-toxin responses1. Giannasca PJ, Warny M. Vaccine. 2004;22:848-856.2. Kyne L, et al. Lancet. 2001;357:189-193; with permission

Median serum concentrations of antibody against toxin A

Ser

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IgG

CDI Diagnostic Challenges

Test Advantage(s) Disadvantage(s)

Toxin testing Enzyme immunoassay

Rapid, simple, inexpensive

Least sensitive method

Tissue culture cytotoxicity

Organism identification

More sensitive than enzyme immunoassay

Labor intensive; requires 24–48 hours for a final result, special equipment

Detection of glutamate dehydrogenase (GDH)

Rapid, sensitive, may prove useful as a triage or screening tool

Not specific, toxin testing required to verify diagnosis; may not be optimally sensitive

PCR Rapid, sensitive, detects presence of toxin gene

Cost, special equipment, does not necessarily indicate the presence of toxin; indiscriminant testing with PCR is a particular concern

Stool culture Most sensitive test available when performed appropriately

Like GDH, may be associated with false-positive results if isolate is not tested for toxin; labor-intensive; not practical for most laboratories

CDI Diagnostic Challenges

• Two- and three-step testing algorithms have been proposed– Initial screen: EIA for glutamate dehydrogenase– Confirmatory: Cell cytotoxicity assay (or

culture) or polymerase chain reaction (PCR)

• Results appear to differ based on the GDH kit used

• Optimal universal strategy remains continuous source of debate

1. Hansen G, et al. Clin Laboratory News. 2010 July:10-13.2. Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.

SHEA/IDSA 2010 Guidelines

for Diagnosis• Testing for C. difficile or its toxins should

be performed only on unformed stool (unless ileus is suspected)1

Brecher rule: “If it ain’t loose, it’s of no use”2

• Testing asymptomatic patients is not clinically useful1

• Test of cure is not recommended1

1.Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455. 2. Dr. Stephen Brecher, verbal communication.

SHEA/IDSA 2010 Guidelines

for Diagnosis (Cont.)• EIA to detect toxin is a suboptimal

alternative approach for diagnosis• 2-step testing can help to overcome low

sensitivity of EIA toxin testing• More data on utility of PCR testing is

necessary before it can be recommended for routine testing (consensus at time of Guidelines publication)

• Repeat testing during same episode of diarrhea is not recommended

Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.

Summary of C. difficile PCR Published Data Compared to

Toxigenic CulturePublication PCR Assay Sensitivity/Specificity

Chapin, 20111 Compared 3 molecular methods

88.5-96.2%/91.6-100% (range)

Noren, 20112 Illumigene 98%/98.%

Kvach, 20103 BD GeneOhm 91.4%/100%

Novak-Weekley, 20104 Cepheid Xpert 94.4%/96.3%

Swindells, 20105 Cepheid XpertBD GeneOhm

100%/99.2%94.4%/99.2%

Slide from Dr. Susan Novak-Weekley modified by Dr. Stephen Brecher

1. Chapin KC, et al. J Mol Diagn. 2011;13:395-400. 2. Norén T, et al. J Clin Microbiol. 2011; 49:710-711. 3. Kvach EJ, et al. J Clin Microbiol. 2010;48:109-114. 4. Novak-Weekley SM, et al. J Clin Microbiol. 2010;48(3):889-893. 5. Swindells J, et al. J Clin Microbiol. 2010;48 (2):606-608.

Early Experience with PCR

– CDI rates initially increase because of increased sensitivity (true prevalence detection)

– Test volume goes down by 50% – Test materials cost offset by

appropriate utilization of antibiotics and infection control protocols

Belmares J, et al. SHEA 2011; Abstract #150.

Basic Principles of CDI Therapy

• Discontinue offending antimicrobial agent (if possible)

• Send stool specimen for C. difficile testing• Initiate CDI therapy either empirically or

following confirmation of diagnosis – Pharmacotherapy

• Vancomycin, Fidaxomicin (only FDA-approved treatments for CDI)

• Metronidazole• Other

– Supportive treatment

• Monitor for symptom resolution and recurrence after treatment

Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.

SHEA/IDSA Treatment Recommendations

Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.

Clinical scenario Supportive clinical data Recommended treatment

Mild to moderate Leukocytosis (WBC < 15,000 cells/uL) or SCr level < 1.5 times premorbid level

Metronidazole 500 mg 3 times per day PO for 10-14 days

Severe Leukocytosis (WBC ≥ 15,000 cells/uL) or SCr level ≥ 1.5 times premorbid level

Vancomycin 125 mg 4 times per day PO for 10-14 days

Severe, complicated Hypotension, shock, ileus, or megacolon

Vancomycin 500 mg 4 times per day PO or by nasogastric tube plus metronidazole 500 mg IV q 8 hrs

Additional Management of

Severe, Complicated CDI• Prompt recognition of severe, complicated CDI and

early surgical evaluation is critical*• Indications of severe, complicated disease course:

– Elevated and rising white blood cell count (WBC)– Elevated serum creatinine (SCr) level– Elevated serum lactate– Clinical and/or radiographic evidence of severe ileus,

impending toxic megacolon

• Consider vancomycin per rectum if ileus is severe

*Colectomy may be lifesaving, but is associated with increased risk of mortality if WBC is > 50,000 and lactate is >5 mg/dL1. Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.

2. Pépin J, et al. Dis Colon Rectum. 2009;52:400-405.

Management of Recurrent CDI

• CDI recurrence is a significant challenge• Rates of recurrent CDI:

– 15-25% after first episode– 30-45% after first recurrence– 40-65% after two or more recurrences

Clinical scenario Recommended treatment

First recurrence Treat as first episode according to disease severity

Second recurrence Treat with oral vancomycin taper and/or pulse dosing

1. Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455. 2. Johnson S. J Infect. 2009;58(6):403-410.3. Pépin J, et al Clin Infect Dis 2006;42:758–764.

Multiple Recurrent CDI• Several empirical approaches have been

advocated but most have no controlled data1-3

• Metronidazole should not be used beyond first recurrence or for prolonged course, ie, >14 days (concerns for hepatotoxicity and polyneuropathy)1-3

• Uncontrolled data with vancomycin taper regimen4,5

1. Aslam S, et al. Lancet Infect Dis. 2005;5:549-557. 2. McFarland LV, et al. Am J Gastroenterol. 2002:97:1769-1775. 3. McFarland LV, et al. JAMA. 1994;271:1913-1918. 4. Kyne L, Kelly CP. Gut. 2001;49:152-153. 5. Tedesco FJ, et al. Am J Gastroenterol. 1985;80:867-868.

Oral Vancomycin Taper125 mg QID x 10-14 days

125 mg BID x 7 days125 mg daily x 7 days

125 mg once every 2 days x 8 days125 mg once every 3 days x 15 days

Recurrent CDI Case

65 year-old man with COPD hospitalized from 8/5 to 8/7/10 and treated for pneumonia with piperacillin/tazobactam, followed by oral moxifloxacin. Of note, patient was treated for C. difficile infection (CDI) in 3/10.• Dx testing: 3/27/10: C. difficile toxin A/B EIA= POSITIVE

3/28/10: C. difficile toxin A/B EIA= POSITIVE 3/28/10: C. difficile toxin A/B EIA= POSITIVE• Rx: Oral metronidazole 500 mg qid

(still on same regimen 4+ months later) WHAT WOULD YOU SAY REGARDING CDI DIAGNOSTIC TESTING?WHAT WOULD YOU RECOMMEND REGARDING CDI TREATMENT?

Recurrent CDI Case (con’t)• Patient was readmitted the day after discharge (8/8/10)

with new onset of diarrhea (4 watery stools, 1 episode of incontinence) and crampy abdominal pains.

• Patient was still on moxifloxacin (metronidazole was discontinued on the day of his recent admission [8/5/10]).

• Dx testing: 8/8/10: C. difficile toxin A/B EIA= NEGATIVE*

WHAT IS YOUR DIFFERENTIAL DIAGNOSIS?WHAT EMPIRIC TREATMENT WOULD YOU START (IF ANY)?*Additional information to be provided by faculty presenter

Newly Available CDI Therapy: Fidaxomicin

• Rate of clinical cure with fidaxomicin non-inferior to that of vancomycin (phase 3 trial results)

• Fidaxomicin associated with significantly lower rate of CDI recurrence & similar adverse event profile

• Results of first phase 3 trial (nearly identical results from 2nd phase 3 trial):

Louie TJ, et al. N Engl J Med. 2011;364:422-431; with permission.

mITT=modified intent to treatPP=per protocol

Newly Available CDI Therapy: Fidaxomicin

• Approved by FDA on May 27, 2011 • Indication and dosing1

-Treatment of Clostridium difficile-associated diarrhea (aka, CDI) in adults (>18 years of age)

-Recommended dose 200 mg orally twice daily for 10 days

• Advantageous characteristics1,2

– Minimal systemic absorption– Bactericidal agent unrelated to agents used for treatment of systemic

infections– Narrow spectrum (less collateral damage to host flora)

• Challenges include– Which patients should receive fidaxomicin treatment?– Hospital formulary inclusion– Post approval monitoring for unanticipated side affects, evidence for

resistance

1. Dificid [package insert]. San Diego, CA: Optimer Pharmaceuticals; 2011.2. Tannock GW, et al. Microbiology. 2010;156(Pt11):3354-9.

Alternative CDI Therapies: Probiotics

• Adjunctive treatment for recurrent CDI– Randomized trials of Lactobacillus species failed to

demonstrate benefit to prevent recurrent CDI

• Saccharomyces boulardii for secondary prophylaxis was promising2,3

– “Confirmatory” trial failed to confirm – Overall no effect: 44% vs 47% recurrence (RR 0.91;

95% confidence interval 0.66 to 1.27)3

• subgroup analysis showed borderline benefit with S. boulardii and high dose vancomycin (p=0.05)

– Reports of fungemia have been reported

• More study needed for probiotics in primary prevention1. Dendukuri N, et al. CMAJ. 2005;173:167-170. 2. Tung JM, et al. Can J Gastroenterol. 2009;23:817-821.3. Surawicz CM, et al. Clin Infect Dis. 2000;31:1012-1017.

Alternative CDI Therapies: Rifaximin

(Not FDA Approved for CDI Treatment)• Rifaximin “chaser” therapy for multiple recurrent CDI

episodes1

– Rifaximin 400 mg BID for 14 days immediately following last course of vancomycin

– Seven of eight patients had no further diarrhea recurrence

– Single case of rifaximin resistance with recurrent CDI after a second course of rifaximin

– Follow up experience with 6 patients• 2 recurred, rifaximin resistance identified in one

• Issues with resistance2

– Rifampin resistance observed in 36.8% of 470 recovered isolates and 81.5% of 205 epidemic clone isolates1. Johnson S, et al. Clin Infect Dis. 2007;44:846-848.

2. Curry SR, et al. Clin Infect Dis. 2009;48:425-429. 3. Johnson S, et al. Anaerobe. 2009; 15:290-1

Alternative CDI Therapies: Nitazoxanide (Not FDA Approved for CDI

Treatment)• May be effective in patients

who failed treatment with metronidazole1

– 66% cure rate in 35 patients who failed treatment with metronidazole

• Non-inferior to vancomycin in small study of 50 patients (Figure)2

– Initial response:• Vancomycin: 87%• Nitazoxanide: 94%

– Similar time to complete resolution of symptoms

Time to resolution of symptoms

P=0.55

1. Musher DM, et al. J Antimicrob Chemother. 2007;59:705-710.2. Musher DM, et al. Clin Infec Dis. 2009;48:e41-e46; with permission.

Alternative Adjunctive Therapies for Severe CDI(Not FDA Approved for CDI Treatment)

• Tigecycline1-3

– Case reports and small case series with IV Tigecycline

– Usually given in conjunction with other therapies for severe CDI

• Intravenous Immunoglobulin4,5

– Several case series in severe CDI, but evidence for benefit is inconclusive

1. Lu CL, et al. Int J Antimicrob Agents. 2010;35:311-312.2. Herpers BL, et al. Clin Infect Dis. 2009;48:1732-1735.3. Kopterides P, et al. Anaesth Intensive Care. 2010;38:755-758.4. Abougergi MS, et al. J Hosp Med. 2010;5:E1-E9.5. O’Horo J, et al. Int J Infect Dis. 2009;13:663-667.

Fecal Flora Restoration

• Theory: Restoration of fecal flora restores colonization resistance

• Data:– 1958 to 2000: 9 reports (68 patients); cure rate ~90%. – 2003: 18 patients; fecal filtrate (stool transplant); 1 of

16 survivors had a single subsequent recurrence; pre-treated with vancomycin and omeprazole; instilled through nasogastric tube.

• Test donor for enteric pathogens, C. difficile, ova and parasites, HAV, HBV, HCV, HIV, RPR prior to transplanting stool.

1. Persky SE, Brandt LJ. Am J Gastroenterol. 2000;95:3283-3285.2. Borody TJ. Am J Gastroenterol. 2000;95:3028-3029.3. Palmer R. Nat Med. 2011;17:150-152.

Potential Future CDI Therapies:

Nontoxigenic C. difficile• Nontoxigenic C. difficile strains

occur naturally• Natural asymptomatic C. difficile

colonization (toxigenic or nontoxigenic) decreases risk of infection

• Nontoxigenic C. difficile can be administered orally as spores to provide protection against CDI– Mechanism by which nontoxigenic

C. difficile prevents colonization by toxigenic strains not yet established

• Human Phase 2 trials began in Q2 2011

1. Gerding DN, Johnson S. Clin Infect Dis. 2010;51:1306-1313.2. Sambol SP, et al. J Infect Dis. 2002;186:1781-1789; with permission

Non-toxigenic C. difficile prevented CDI in 87%-97%

of hamsters

M3, M23, T7 = non-toxigenic CD

B1, J9, K14 = toxigenic CD

Potential Future CDI Therapies:

Monoclonal Antibodies (mAbs)• Recent study of mAbs in 200 CDI patients

receiving metronidazole or vancomycin• Recurrence rates:

– 7% in mAb group vs. 25% in placebo group

Lowry I, et al. N Engl J Med. 2010;362:197-205; with permission.

Time to CDI recurrence

Prevention of CDI• Transmission between patients and healthcare

professionals in hospitals is major source of C. difficile acquisition

• Surveys report inconsistencies among infection control measures1

– Hand hygiene policies – Duration of isolation– Environmental cleaning practices– Antimicrobial stewardship programs

• Potential future intervention of toxoid vaccine2

1. APIC 2010 Clostridium difficile Pace of Progress Survey. Available at: http://www.apic.org/Content/NavigationMenu/ResearchFoundation/NationalCDiffPrevalanceStudy/CDI_Pace_of_Progress_Survey_Report.pdf

2. Foglia G, et al. Anarobe Society of Americas 2010; Abstract CD 1093.

Minimize Transmission among Healthcare Personnel: Hand

Hygiene• Appropriate hand hygiene – area of

controversy– In routine settings, alcohol-based hand

hygiene in conjunction with isolation precautions using gloves may be acceptable

– In setting of outbreak or increased rates, consider washing hands with soap and water after caring for patients with C. difficile

HCWs = healthcare workers.

1. Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31:431-455.2. Dubberke ER, et al. Infect Control Hosp Epidemiol. 2008;29:S81-S92.3. APIC Guide to the Elimination of Clostridium difficile in Healthcare Settings, Association for Professionals in Infection Control and Epidemiology, Inc. November 2008.

Efficacy of Hand Hygiene Methods

for Removal of C. difficile Contamination from Hands

* Different from AHR (P<0.05).

** Different from AHR and AHW (P<0.05).

*

Oughton M, et al. Infect Control Hosp Epidemiol. 2009;30(10):939-944.

Decrease in colony countscompared with no wash

1.8 1.81.4

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WWS CWS WWA AHW AHR

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WWS=warm water and soapCWS=cold water and soapWWA=warm water and antibacterial soapAHW=alcohol hand wipeAHR=alcohol hand rub

Minimize Transmission Among Healthcare

Personnel: Use of Gloves• Four wards randomized• Intervention

– Education: gloves when handling body substances (stool, blood, urine)

– Gloves placed at bedside

• Significant reduction in CDI rate on glove wards

P = 0.015

Johnson S, et al. Am J Med. 1990;88:137-140.

Minimize Transmission Among Healthcare Personnel: Contact

Precautions• Patients with CDI placed in private rooms

when possible• Full barrier precautions (gown and gloves)

for contact with CDI patient• Use of dedicated patient care items and

equipment

1. Dubberke ER, et al. Infect Control Hosp Epidemiol. 2008;29:S81-S92.2. Cohen SH, et al. Infect Control Hosp Epidemiol. 2010;31(5):431-455.

Minimize Transmission from

Environment: Disinfection• Use of sodium hypochlorite (at least 5,000 ppm

available chlorine) for environmental contamination, during outbreak areas

• Inconsistent efficacy in endemic settings• Areas in question:

– Concentration of bleach? [Available chlorine: 5,000 ppm (1:10), 1,000 ppm, or 500ppm]

– Where to clean? [CDI rooms only, all rooms, entire ward]– How frequent? [Daily or upon discharge]– How to implement? [Mix fresh daily, premixed, or

prepackaged wipes; wipe or spray]

Perez. J, et al. Am J Infect Control. 2005;33:320-325.

Minimize Transmission by Environment: Bleach

Disinfection

Mayfield JL, et al. Clin Infect Dis. 2000;31:995-1000.

Reduce Risk of CDI Acquisition: Antimicrobial

Stewardship• Reduce use of “high

risk” antimicrobials• Reduce unnecessary

antimicrobial use• Effective in outbreak

and non-outbreak settings

1. Valiquette L. Clin Infect Dis. 2007;45:S112-121; with permission.2. Fowler S. J Antimicrob Chemother. 2007;59:990-995.

Reduction in CDI after Bundle*(*enhanced isolation practices, laboratory notification procedures, coordination of infection

control & environmental services activities)

• CDI incidence decreased from 11.0 to 6.6 cases / 10,000 patient days (P<0.001)

• Data on compliance with policies before or after bundle lacking– Unclear what parts of bundle were effective

Abbett SK, et al. Infect Control Hosp Epidemiol. 2009; 30:1062-1069.

CDI: Future Direction

• Optimal diagnostic algorithm for CDI• Prompt recognition of severe CDI • Validation of risk-stratified treatment for CDI• CDI recurrence prevention and treatment• Expanding armamentarium for CDI (both

antibiotic and non-antibiotic approaches)• Delineation of the most effective infection

control measures—which aspects of the “CDI bundle” are important?