Prevention of Infection Due to Endoscopy William A. Rutala, Ph.D., M.P.H. University of North Carolina (UNC) Health Care System and UNC at Chapel Hill

Disclosure This educational activity is brought to you, in part, by Advanced Sterilization Products (ASP) and Ethicon. The speaker receives an honorarium from ASP and Ethicon and must present information in compliance with FDA requirements applicable to ASP.

Endoscope Reprocessing Lecture Goals Background Infections related to endoscopy Reprocessing of endoscopes and accessories Cleaning High-level disinfection/sterilization Automated endoscope reprocessing Quality control

GI ENDOSCOPES Widely used diagnostic and therapeutic procedure Endoscope contamination during use (109 in/105 out) Semicritical items require high-level disinfection minimally Inappropriate cleaning and disinfection has lead to cross-transmission In the inanimate environment, although the incidence remains very low, endoscopes represent a risk of disease transmission

TRANSMISSION OF INFECTION Gastrointestinal endoscopy >300 infections transmitted 70% agents Salmonella sp. and P. aeruginosa Clinical spectrum ranged from colonization to death (~4%) Bronchoscopy 90 infections transmitted M. tuberculosis, atypical Mycobacteria, P. aeruginosa Spach DH et al Ann Intern Med 1993: 118:117-128 and Weber DJ, Rutala WA Gastroint Dis 2002

Nosocomial Infections via GI Endoscopes Observations Number of reported infections is small, suggesting a very low incidence Endemic transmission may go unrecognized (e.g., inadequate surveillance, low frequency, asymptomatic infections) Spach DH. Ann Int Med 1993;118:117 and Weber DJ, Rutala, WA. Gastroint Dis 2002

Nosocomial Infections via GI Endoscopes Infections traced to deficient practices Inadequate cleaning (clean all channels) Inappropriate/ineffective disinfection (time exposure, perfuse channels, test concentration, ineffective disinfectant, inappropriate disinfectant) Failure to follow recommended disinfection practices (tapwater rinse) Flaws is design of endoscopes or AERs

Endoscope Reprocessing: Current Status of Cleaning and Disinfection Guidelines Multi-Society Guideline, 11 professional organizations, 2003 Society of Gastroenterology Nurses and Associates, 2000 European Society of Gastrointestinal Endoscopy, 2000 British Society of Gastroenterology Endoscopy, 1998 Gastroenterological Society of Australia, 1999 Gastroenterological Nurses Society of Australia, 1999 American Society for Gastrointestinal Endoscopy, 1996 Association for Professional in Infection Control and Epidemiology, 2000 Centers for Disease Control and Prevention, 2008 (in press)

Endoscope Reprocessing, Worldwide Worldwide, endoscopy reprocessing varies greatly India, of 133 endoscopy centers, only 1/3 performed even a minimum disinfection (1% glut for 2 min) Brazil, “a high standard …occur only exceptionally” Western Europe, >30% did not adequately disinfect Japan, found “exceedingly poor” disinfection protocols US, 25% of endoscopes revealed >100,000 bacteria Schembre DB. Gastroint Endoscopy 2000;10:215

Endoscopes

ENDOSCOPE DISINFECTION CLEAN-mechanically cleaned with water and enzymatic cleaner HLD/STERILIZE-immerse scope and perfuse HLD/sterilant through all channels for exposure time RINSE-scope and channels rinsed with sterile water, filtered water, or tap water followed by alcohol DRY-use forced air to dry insertion tube and channels STORE-prevent recontamination

ENDOSCOPE REPROCESSING Source of contamination for infections (36 outbreaks) transmitted by GI endoscopes from 1974-2001: Cleaning-3 (12%) Disinfection-19 (73%) Rinse, Dry, Store-3 (12%) Etiology unknown-11

ENDOSCOPE DISINFECTION Cleaning (results in dramatic decrease in bioburden, 4-5 log10 reduction) No brushing biopsy channel. (Schousboe M. NZ Med J 1980;92:275) No precleaning before AER. (Hawkey PM. J Hosp Inf 1981;2:373) Biopsy-suction channel not cleaned with a brush. (Bronowicki JP. NEJM 1997;337:237)

Bacterial Bioburden Associated with Endoscopes Gastroscope, log10 CFU Colonoscope, log10 CFU After procedure 6.7 8.5 Gastro Nursing 1998;22:63 6.8 8.5 Am J Inf Cont 1999;27:392 9.8 Gastro Endosc 1997;48:137 After cleaning 2.0 2.3 4.8 4.3 5.1

Viral Bioburden from Endoscopes Used with AIDS Patients Hanson et al Viral Bioburden from Endoscopes Used with AIDS Patients Hanson et al. Lancet 1989;2:86; Hanson et al. Thorax 1991;46:410 Dirty Cleaned Disinfected Gastroscopes HIV (PCR) 7/20 0/20 HBsAg 1/20 0/7 Bronchoscopes HIV (cDNA) 7/7 1/10 0/10

ENDOSCOPE REPROCESSING Precleaning After removal from patient, wipe the insertion tube with a wet cloth and alternate suctioning the enzymatic cleaner and air through the biopsy/suction channel until solution clean. The air-water channel is flushed or blown out per instructions. Transport the endoscope to the reprocessing area. Enyzmatic cleaner should be prepared per instructions. Some data suggest enzymes are more effective cleaners than detergents. Enyzmatic cleaners must be changed after use.

ENDOSCOPE REPROCESSING Cleaning Immerse in a compatible low-sudsing, enzymatic cleaner Wash all debris from exterior by brushing and wiping Remove all removal parts of the endoscope and clean each reusable part separately After exterior cleaning, brush accessible channels with appropriate-sized cleaning brush

ENDOSCOPE REPROCESSING Cleaning (continued) After each passage, rinse the brush, remove debris before reinserting. Continue until no visible debris on brush. Attach cleaning adapters for each channel per manufacturer’s instructions and flush with enzymatic cleaner to remove debris. After cleaning is complete, rinse the endoscope with clean water. Purge water from channels using forced air. Dry exterior of the endoscope with a soft, lint-free cloth.

ENDOSCOPE DISINFECTION CLEAN-mechanically cleaned with water and enzymatic detergent HLD/STERILIZE-immerse scope and perfuse HLD/sterilant through all channels for exposure time RINSE-scope and channels rinsed with sterile water, filtered water, or tap water followed by alcohol DRY-use forced air to dry insertion tube and channels STORE-prevent recontamination

ENDOSCOPE REPROCESSING Source of contaminations for infections (36 outbreaks) transmitted by GI endoscopes from 1974-2001: Cleaning-3 (12%) Disinfection-19 (73%) Rinse, Dry, Store-3 (12%) Etiology unknown-11

ENDOSCOPE REPROCESSING Unacceptable Disinfectants for HLD Benzalkonium chloride Iodophor Hexachlorophene Alcohol Chlorhexidine gluconate Cetrimide Quaternary ammonium compounds Glutaraldehyde (0.13%) with phenol

ENDOSCOPE REPROCESSING Inappropriate disinfectants Benzalkonium chloride (Greene WH. Gastroenterol 1974;67:912) 70% alcohol (Elson CO. Gastroenterol 1975;69:507) QUAT (Tuffnell PG. Canad J Publ Health 1976;67:141) Hexachlorophene (Dean AG. Lancet 1977;2:134) Hexachlorophene (Beecham HJ. JAMA 1979;1013) 70% alcohol (Parker HW. Gastro Endos 1979;25;102) Povidone-iodine (Low DE. Arch Intern Med 1980;1076) Cetrimonium bromide. (Schliessler KH. Lancet 1980;2:1246)

ENDOSCOPE REPROCESSING Inappropriate disinfectants 3% hexachlorophene. (Schousboe M. NZ Med J 1980;92:275) 0.5% CHG in alcohol, 0.015% CHG and 0.15% cetrimide; 87 s exposure to 2% glut. (Hawkey PM. J Hosp Inf 1981;2:373) 1% Savlon (cetrimide and CHG).(O’Connor BH. Lancet 1982;2:864) 0.0075% iodophor. (Dwyer DM. Gastroint Endosc 1987;33:84) 0.13% glut with phenol. (Classen DC. Am J Med 1988;84:590) 70% ethanol for 3 min. (Langenberg W. J Inf Dis 1990;161:507)

ENDOSCOPE REPROCESSING Inappropriate disinfection Air/water channel not exposed to glut. (Birnie GG. Gut 1983;24:171) Air/water channel not exposed to glut. (Cryan EMJ. J Hosp Inf 1984;5:371) No glut (water only) between patients. (Earnshaw JJ. J Hosp Inf 1985;6:95)

High Level Disinfection of “Semicritical Objects” Exposure Time > 12 m-30m (US), 20oC Germicide Concentration_____ Glutaraldehyde > 2.0% Ortho-phthalaldehyde (12 m) 0.55% Hydrogen peroxide* 7.5% Hydrogen peroxide and peracetic acid* 1.0%/0.08% Hydrogen peroxide and peracetic acid* 7.5%/0.23% Hypochlorite (free chlorine)* 650-675 ppm Glut and phenol/phenate** 1.21%/1.93%___ *May cause cosmetic and functional damage; **efficacy not verified

New FDA-Cleared Sterilants/HLD “Older” > 2% Glut, 7.5% HP, 1.0% HP and 0.08% PA Newer 0.55% ortho-phthalaldehyde (HLD- 5 m worldwide, 12 m in US) 0.95% glut and 1.64% phenol/phenate (HLD-20 m at 25oC) 7.5% HP and 0.23% PA (HLD-15 m) 2.5% Glut (HLD-5 m at 35oC) Ensure antimicrobial activity and material compatibility

Ideal HLD/Chemical Sterilant Rapid HLD (< 10 min) No disinfectant residue after rinsing Excellent material compatibility Long shelf-life Nontoxic (no odor or irritation issues) No disposal problems Monitor minimum effective concentration

Glutaraldehyde Numerous use studies published Relatively inexpensive Advantages Numerous use studies published Relatively inexpensive Excellent materials compatibility Disadvantages Respiratory irritation from vapor (ACGIH 0.05 ppm) Pungent and irritating odor Relatively slow mycobactericidal activity Coagulate blood and fix tissues to surfaces

Ortho-phthalaldehyde Advantages Fast acting HLD No activation Excellent materials compatibility Not a known irritant to eyes and nasal passages Weak odor Disadvantages Stains protein gray Cost ($30/gal);but lower reprocessing costs-soak time, devices per gal) Slow sporicidal activity Eye irritation with contact Exposure may result in hypersensitivity

Comparison of Glutaraldehyde and OPA HLD: 45 min at 25oC Needs activator 14 day use life 2 year shelf life ACGIH ceiling limit, 0.05ppm Strong odor MEC, 1.5% Cost - $12/gallon 0.55% Ortho-phthalaldehyde HLD: 12 min at 20oC No activator needed 14 day use life 2 year shelf life No ACGIH or OSHA limit Weak odor MEC, 0.3% Cost - $30/gallon

OPA Research Alfa and Sitter, 1994. OPA eliminated all microorganisms from 100 different endoscopes used in a clinical setting. Gregory et al, 1999. OPA achieved a 6 log10 reduction of M. bovis in 5.5 min compared to 32 min for glutaraldehyde Walsh et al, 1999. OPA effective against glutaraldehyde-resistant M. chelonae strains

OPA Label Claims Worldwide 1. Europe, Asia, Latin America 5 min at 20oC 2. Canada and Australia 10 min at 20oC 3. United States 12 min at 20oC 1. Antimicrobial tests support 5 min exposure time. 2. Canadian regulatory authority requires 6-log reduction in mycobacteria (5.5 m) and only 5 min intervals. 3. FDA requires 6-log reduction of mycobacteria suspended in organics and dried onto scope without cleaning

Ortho-phthalaldehyde (OPA) Contraindication for OPA Repeated exposure to OPA, following manual reprocessing of urological instruments, may have resulted in hypersensitivity in some patients with a history of bladder cancer undergoing repeated cystoscopy. Out of approximately 1 million urological procedures, there have been reports of 24 patients who have experience ‘anaphylaxis-like’ reactions after repeated cystoscopy (typically after 4-9 treatments). Risk control measures: residues of OPA minimized; and contraindicated for reprocessing of urological instruments used on patients with history of bladder cancer.

Hydrogen Peroxide Disadvantages Advantages No activation required Enhanced removal of organisms No disposal issues No odor or irritation issues Does not coagulate blood or fix tissues to surfaces Use studies published Disadvantages Material compatibility concerns for brass, zinc, copper, and nickel/silver plating (cosmetic and functional damage) Eye damage with contact

Peracetic Acid/Hydrogen Peroxide Advantages No activation required No odor or irritation issues Effective in the presence of organic matter Disadvantages Material compatibility issues for lead, brass, copper, zinc (both cosmetic and functional damage for 1% HP with 0.08% PA) Limited clinical use

Minimum Effective Concentration (MEC) High Level Disinfectant (HLD) Dilution of HLD occurs during use Test strips are available for monitoring MEC For example, test strips for glutaraldehyde monitor 1.5% Test strip not used to extend the use-life beyond the expiration date (date test strips when opened) Testing frequency based on how frequently the solutions are used (used daily, test at least daily) Record results

Endoscope Reprocessing Disinfectant/Sterilant Immerse the endoscope in HLD/sterilant (at least 12-20 minutes) and fill the channels with HLD/sterilant until no air bubbles are seen Reusable endoscopic accessories that break the mucosal barrier (e.g., biopsy forceps) should be mechanically cleaned as described above and then sterilized between each patient use. Rinsing Rinse all surfaces and channels and removable parts with clean water to remove disinfectant. Inadequate rinsing of HLD has caused colitis. Drying and Alcohol Flush Purge channels with air; flush with alcohol; purge with air; dry Store-prevent recontamination

ENDOSCOPE REPROCESSING Rinse, Dry, Store Irrigating water bottle. (Doherty DE. Dig Dis Sci 1982;27:169) Inadequate drying (no alcohol). (Allen JI. Gastroenterol 1987;92:759) Inadequate drying (no alcohol). (Classen DC. Am J Med 1988;84:590)

ENDOSCOPE REPROCESSING Rinse/Drying/ Storage after Manual Disinfection Thoroughly rinse all surfaces and channels of the endoscope with large amounts of clean water Filtered or sterile water is preferred but not mandatory Inadequate rinsing of HLD has caused colitis Purge all channels with air, flush with alcohol (assists drying), purge channels with air, dry the exterior Hang the endoscope vertically (eg, cabinet)

Nosocomial Outbreaks via GI Endoscopes Infections Associated with Accessories Biopsy forceps Contaminated biopsy forceps. (Dwyer DM. Gastroint Endosc 1987;33:84) Contaminated biopsy forceps (no cleaning between cases). Graham DY. Am J Gastroenterol 1988;83:974) Biopsy forceps not sterilized (glut exposed,? time) Bronowicki JP. NEJM 1997;334:237)

ENDOSCOPE REPROCESSING Manual/AER HLD High level disinfection is the standard of care for reprocessing GI endoscopes and bronchoscopes The process can be completed manually or with an AER Until recently no automated endoscope reprocessor (AER) substitutes for manual cleaning For manual disinfection, immerse completely in HLD and fill each channel with the HLD Cover the basin to prevent vaporization and use timer Flush channels with air before removing the scope from HLD

Automated Endoscope Reprocessors (AERs) Advantages: automate and standardize reprocessing steps, reduce personnel exposure to chemicals, filtered tap water Disadvantages: failure of AERs linked to outbreaks, does not eliminate precleaning, does not monitor HLD concentration Problems: incompatible AER (side-viewing duodenoscope); biofilm buildup; contaminated AER; inadequate channel connectors MMWR 1999;48:557. Used wrong set-up or connector Must ensure exposure of internal surfaces with HLD/sterilant

EVOTECH w/Cleaning Claim Product Definition: Integrated double-bay AER Eliminates manual cleaning Uses New High-Level Disinfectant (HLD) with IP protection Single-shot HLD Automated testing of endoscope channels and minimum effective concentration of HLD Incorporates additional features (LAN, LCD display)

Endoscope Processing System Reliance™ EPS Endoscope Processing System Reliance™ DG Endoscope Processing Support Klenzyme®, CIP® 200 Reliance™ PI

Automatic Endoscope Reprocessors EvoTech-integrates cleaning (FDA-cleared claim) and disinfection. Automated cleaning comparable to manual cleaning. All residual data for cleaning of the internal channels as well as external insertion tube surfaces were below the limit of <8.5ug/cm2 Reliance-requires a minimal number of connections to the endoscope channels and uses a control boot (housing apparatus the creates pressure differentials to ensure connectorless fluid flow through all channels that are accessible through the endoscope’s control handle channel ports). Data demonstrate that the soil and microbial removal effected by Reliance washing phase was equivalent to that achieved by optimal manual cleaning. Alfa, Olson, DeGagne. AJIC 2006;34:561.

HLD versus Sterilization for Endoscopes

Sterilization (S) or High-Level Disinfection (HLD) Burns and colleagues compared S versus HLD with glut for arthroscopes and laparoscopes and found no difference (7.5/1000 procedures for S vs. 2.5/1000 procedures for HLD) Burns et al Infect Control Hosp Epidemiol 1996; 17: suppl p42 Fuselier and Mason examined S (with peracetic acid) and glut and found no clinical difference (no clinical data). S about 10 more costly than HLD. Fuselier and Mason Urology 1997; 50:337 Thus, no data S is superior to HLD

ENDOSCOPE REPROCESSING Staff Safety Personal Protective Equipment Gloves Eye protection Impervious gown Personnel who use chemicals should be educated about the biologic and chemical hazards present while performing procedures that use disinfectants Reprocessing Room Area designated for this function with: adequate space, proper airflow and ventilation (7-15 ACH), work flow patterns

Disinfection of Emerging Pathogens

Disinfection and Sterilization of Emerging Pathogens Hepatitis C virus Clostridium difficile Cryptosporidium Helicobacter pylori E.coli 0157:H7 SARS coronavirus Antibiotic-resistant microbes (MDR-TB, VRE, MRSA) Creutzfeldt-Jakob disease (no brain, eye, spinal cord contact)

Disinfection and Sterilization of Emerging Pathogens Standard disinfection and sterilization procedures for patient care equipment are adequate to sterilize or disinfect instruments or devices contaminated with blood and other body fluids from persons infected with emerging pathogens

Clostridium difficile

Disinfectants and Antiseptics C Disinfectants and Antiseptics C. difficile spores at 10 and 20 min, Rutala et al, 2006 ~4 log10 reduction (3 C. difficile strains including BI-9) Clorox, 1:10, ~6,000 ppm chlorine (but not 1:50, ~1,200 ppm) Clorox Clean-up, ~1,910 ppm chlorine Tilex, ~25,000 ppm chlorine Steris 20 sterilant, 0.35% peracetic acid Cidex, 2.4% glutaraldehyde Cidex-OPA, 0.55% OPA Wavicide, 2.65% glutaraldehyde Aldahol, 3.4% glutaraldehyde and 26% alcohol

Control Measures C. difficile Handwashing (soap and water) , contact precautions, and meticulous environmental cleaning (disinfect all surfaces) with an EPA-registered disinfectant should be effective in preventing the spread of the organism. McFarland et al. NEJM 1989;320:204. In units with high endemic C. difficile infection rates or in an outbreak setting, use dilute solutions of 5.25-6.15% sodium hypochlorite (e.g., 1:10 dilution of bleach) for routine disinfection. (Category II) For semicritical equipment, glutaraldehyde (20m), OPA (12m) and peracetic acid (12m) reliably kills C. difficile spores using normal exposure times

High-Level Disinfection C. difficile spores 2% glutaraldehyde is effective against C. difficile at 20 minutes 0.55% ortho-phthalaldehyde is effective against C. difficile at 10 minutes Steris 20 is effective against C. difficile at 10 and 20 minutes

ENDOSCOPE SAFETY Quality Control Ensure protocols equivalent to guidelines from professional organizations (APIC, SGNA, ASGE) Are the staff who reprocess the endoscope specifically trained in that job? Are the staff competency tested at least annually? Conduct IC rounds to ensure compliance with policy Consider microbiologic sampling of the endoscope

Conclusions Endoscopes represent a nosocomial hazard Proper cleaning and disinfection will prevent nosocomial transmission Current guidelines should be strictly followed Compliance must be monitored Safety and efficacy of new technologies must be validated

Prevention of Infection Due to Endoscopy Background Infections related to endoscopy Processing of endoscopes and accessories Cleaning High-level disinfection/sterilization Automated endoscope reprocessing Quality control

Thank you

References Rutala WA, Weber DJ. Disinfection of endoscopes: Review of new chemical sterilants for high-level disinfection. Infect Control Hosp Epidemiol 1999;20:69-76. Rutala WA, Weber DJ. Creutzfeldt-Jakob Disease: Recommendations for disinfection and sterilization. Clin Inf Dis 2001;32:1348-1356. Society of Gastroenterology Nurses and Associates. Standards. 2000. Weber DJ, WA Rutala, AJ DiMarino. Prevention of infection following gastrointestinal endoscopy. Gastro Dis. 2002;87-107 Rutala WA, Weber DJ, HICPAC. Disinfection and sterilization in healthcare facilities. MMWR. In press.