Elaine L. Larson Lectureship Disinfection and Sterilization: From Benchtop to Bedside William A. Rutala, Ph.D., M.P.H., C.I.C. University of North Carolina (UNC) Health Care and UNC at Chapel Hill, NC

Disinfection and Sterilization: From Benchtop to Bedside Improved products/processes/technologies  Low-temperature sterilization technology, rapid readout BIs, improved HLD/LLD, wipes, microfiber Improved knowledge  Emerging pathogens- C. difficile, Norovirus, MDROs  The role of the environment in disease transmission Guidelines-integration of science into practice and improved patient care

DISCLOSURES Consultation Advanced Sterilization Products, Clorox Honoraria (speaking) Advanced Sterilization Products, 3M Grants CDC

Disinfection and Sterilization: From Benchtop to Bedside Improved products/processes/technologies  Low-temperature sterilization technology, rapid readout BIs, improved HLD/LLD, wipes, microfiber Improved knowledge  Emerging pathogens- C. difficile, Norovirus, MDROs  The role of the environment in disease transmission Guidelines-integration of science into practice and improved patient care

DISINFECTION AND STERILIZATION EH Spaulding believed that how an object will be disinfected depended on the object’s intended use CRITICAL - objects which enter normally sterile tissue or the vascular system or through which blood flows should be sterile SEMICRITICAL - objects that touch mucous membranes or skin that is not intact require a disinfection process (high-level disinfection[HLD]) that kills all microorganisms but high numbers of bacterial spores NONCRITICAL - objects that touch only intact skin require low- level disinfection

New Trends in Sterilization of Patient Equipment Alternatives to ETO-CFC ETO-CO 2, ETO-HCFC, 100% ETO New Low Temperature Sterilization Technology Hydrogen Peroxide Gas Plasma-most common Vaporized hydrogen peroxide Ozone

Rapid Readout BIs for Steam Required a 1-3h Readout Compared to 24-48h

DISINFECTION AND STERILIZATION EH Spaulding believed that how an object will be disinfected depended on the object’s intended use CRITICAL - objects which enter normally sterile tissue or the vascular system or through which blood flows should be sterile SEMICRITICAL - objects that touch mucous membranes or skin that is not intact require a disinfection process (high-level disinfection[HLD]) that kills all microorganisms but high numbers of bacterial spores NONCRITICAL - objects that touch only intact skin require low- level disinfection

High-Level Disinfection of “Semicritical Objects” Exposure Time > 8m-45m (US), 20 o C Germicide Concentration_____ Glutaraldehyde > 2.0% Ortho-phthalaldehyde 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)* ppm Accelerated hydrogen peroxide 2.0% Peracetic acid 0.2% Glut and isopropanol 3.4%/26% Glut and phenol/phenate** 1.21%/1.93%___ * May cause cosmetic and functional damage; **efficacy not verified

DISINFECTION AND STERILIZATION Rutala, Weber, HICPAC EH Spaulding believed that how an object will be disinfected depended on the object’s intended use CRITICAL - objects which enter normally sterile tissue or the vascular system or through which blood flows should be sterile SEMICRITICAL - objects that touch mucous membranes or skin that is not intact require a disinfection process (high-level disinfection[HLD]) that kills all microorganisms but high numbers of bacterial spores NONCRITICAL - objects that touch only intact skin require low- level disinfection

LOW-LEVEL DISINFECTION FOR NONCRITICAL EQUIPMENT AND SURFACES Exposure time > 1 min Germicide Use Concentration Ethyl or isopropyl alcohol70-90% Chlorine100ppm (1:500 dilution) Phenolic UD Iodophor UD Quaternary ammonium UD Improved hydrogen peroxide (HP) 0.5%, 1.4% ____________________________________________________ UD=Manufacturer’s recommended use dilution

IMPROVED HYDROGEN PEROXIDE (HP) SURFACE DISINFECTANT Advantages 30 sec -1 min bactericidal and virucidal claim (fastest non-bleach contact time) 5 min mycobactericidal claim Safe for workers (lowest EPA toxicity category, IV) Benign for the environment; noncorrosive; surface compatible One step cleaner-disinfectant No harsh chemical odor EPA registered (0.5% RTU, 1.4% RTU, wet wipe) Disadvantages More expensive than QUAT

BACTERICIDAL ACTIVITY OF DISINFECTANTS (log 10 reduction) WITH A CONTACT TIME OF 1m WITH/WITHOUT FCS. Rutala et al. ICHE. In press OrganismOxivir-0.5%0.5% HPClorox HC HP Cleaner-Dis 1.4% 1.4% HP3.0% HPA456-II QUAT MRSA>6.6<4.0>6.5< VRE>6.3<3.6>6.1< MDR- Ab >6.8<4.3>6.7<4.3 >6.8 MRSA, FCS>6.7NT>6.7NT<4.2 VRE, FCS>6.3NT>6.3NT<3.8 MDR- Ab, FCS >6.6NT>6.6NT<4.1>6.6 Improved hydrogen peroxide is significantly superior to standard HP at same concentration and superior or similar to the QUAT tested

CONTACT TIMES Follow the EPA-registered contact times, ideally Some products have achievable contact times for bacteria/viruses (30 seconds-2 minutes) Other products have non-achievable contact times If use a product with non-achievable contact time Use >1 minutes based on CDC guideline and scientific literature Prepare a risk assessment

Hospital Privacy Curtains (sprayed “grab area” 3x from 6-8” with IHP and allowed 2 minute contact)

Decontamination of Curtains with Improved HP Rutala, Gergen, Weber CP for:Before Disinfection CFU/5 Rodacs (#Path) After Disinfection CFU/5 Rodacs (#Path) % Reduction MRSA330 (10 MRSA)21*(0 MRSA)93.6% MRSA186 (24 VRE)4* (0 VRE)97.9% MRSA108 (10 VRE)2* (0 VRE)98.2% VRE 75 (4 VRE)0 (0 VRE)100% VRE68 (2 MRSA)2* (0 MRSA)97.1% VRE98 (40 VRE)1* (0 VRE)99.0% MRSA618 (341 MRSA)1* (0 MRSA)99.8% MRSA55 (1 VRE)0 (0 MRSA)100% MRSA, VRE320 (0 MRSA, 0 VRE)1* (0 MRSA, 0 VRE)99.7% MRSA288 (0 MRSA)1* (0 MRSA)99.7% Mean2146/10=215 (432/10=44)33*/10=3 (0)98.5% * All isolates after disinfection were Bacillus sp

Wipes Cotton, Disposable, Microfiber Wipe should have sufficient wetness to achieve the disinfectant contact time. Discontinue use of the wipe if no longer leaves the surface visibly wet for > 1m

SURFACE DISINFECTION Effectiveness of Different Methods, Rutala et al Technique (with cotton)MRSA Log 10 Reduction (QUAT) Saturated cloth4.41 Spray (10s) and wipe4.41 Spray, wipe, spray (1m), wipe4.41 Spray4.41 Spray, wipe, spray (until dry)4.41 Disposable wipe with QUAT4.55 Control: detergent2.88

Microfiber Microfiber demonstrated superior microbial removal compared to cotton mop with detergent; use of disinfectant did not improve microbial elimination demonstrated by the microfiber

Disinfection and Sterilization: From Benchtop to Bedside Improved products/processes/technologies  Low-temperature sterilization technology, rapid readout BIs, improved HLD/LLD, wipes, microfiber Improved knowledge  Emerging pathogens- C. difficile, Norovirus, MDROs  The role of the environment in disease transmission Guidelines-integration of science into practice and improved patient care

Decreasing Order of Resistance of Microorganisms to Disinfectants/Sterilants Prions Spores ( C. difficile ) Mycobacteria Non-Enveloped Viruses (norovirus) Fungi Bacteria (MRSA, VRE, Acinetobacter ) Enveloped Viruses Most Susceptible Most Resistant

DISINFECTANTS AND ANTISEPSIS C. difficile spores at 10 and 20 min, Rutala et al, 2006 ~4 log 10 reduction (3 C. difficile strains including BI-9) Clorox, 1:10, ~6,000 ppm chlorine (but not 1:50) Clorox Clean-up, ~19,100 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

C. difficile CONTROL MEASURES Orenstein et al. ICHE 2011;32:1137 In units with high endemic C. difficile infection rates or in an outbreak setting, use dilute solutions of % sodium hypochlorite (e.g., 1:10 dilution of bleach) for routine disinfection. (Category II). We now use chlorine solution in all CDI rooms for routine daily and terminal cleaning (formerly used QUAT in patient rooms with sporadic CDI). One application of an effective product covering all surfaces to allow a sufficient wetness for > 1 minute contact time. Chlorine solution normally takes 1-3 minutes to dry. For semicritical equipment, glutaraldehyde (20m), OPA (12m) and peracetic acid (12m) reliably kills C. difficile spores using normal exposure times

INACTIVATION OF MURINE AND HUMAN NOROVIRUES Disinfectant, 1 minMNV Log 10 ReductionHNV Log 10 Reduction 70% Ethanol>4 (3.3 at 15sec) 2 70% Isopropyl alcohol % Ethanol + QUAT> % Ethanol + QUAT Chlorine (5,000ppm) 4 3 Chlorine (24,000ppm) Phenolic, QUAT, Ag, 3% H <1 <1<1 (2.1 QUAT) 0.5% Accel H Rutala WA, Folan MP, Tallon LA, Lyman WH, Park GW, Sobsey MD, Weber DJ. 2007

WOULD OUR QUAT KILL MRSA? Rutala et al. J Clin Microbiol. 1983;18:683

SUSCEPTIBILITY OF RESISTANT BACTERIA TO DISINFECTANTS Rutala et al. ICHE 1997;18:417 No relationship between antibiotic resistance and disinfectant resistance

EFFECTIVENESS OF DISINFECTANTS AGAINST MRSA AND VRE Antibiotic resistance does not correlate to increased resistance to disinfectants Rutala WA, et al. Infect Control Hosp Epidemiol 2000;21:33-38.

Disinfection and Sterilization: From Benchtop to Bedside Improved products/processes/technologies  Low-temperature sterilization technology, rapid readout BIs, improved HLD/LLD, wipes, microfiber Improved knowledge  Emerging pathogens- C. difficile, Norovirus, MDROs  The role of the environment in disease transmission Guidelines-integration of science into practice and improved patient care

ENVIRONMENTAL CONTAMINATION LEADS TO HAIs There is increasing evidence to support the contribution of the environment to disease transmission This supports comprehensive disinfecting regimens (goal is not sterilization) to reduce the risk of acquiring a pathogen from the healthcare environment

KEY PATHOGENS WHERE ENVIRONMENTIAL SURFACES PLAY A ROLE IN TRANSMISSION MRSA VRE Acinetobacter spp. Clostridium difficile Norovirus Rotavirus SARS

Thoroughness of Environmental Cleaning Carling et al. ECCMID, Milan, Italy, May 2011 Mean = 32% >110,000 Objects

ENVIRONMENTAL CONTAMINATION LEADS TO HAIs Weber, Rutala, Miller et al. AJIC 2010;38:S25 Microbial persistence in the environment In vitro studies and environmental samples MRSA, VRE, AB, CDI Frequent environmental contamination MRSA, VRE, AB, CDI HCW hand contamination MRSA, VRE, AB, CDI Relationship between level of environmental contamination and hand contamination CDI

ENVIRONMENTAL CONTAMINATION LEADS TO HAIS Weber, Rutala, Miller et al. AJIC 2010;38:S25 Person-to-person transmission Molecular link MRSA, VRE, AB, CDI Housing in a room previously occupied by a patient with the pathogen of interest is a risk factor for disease MRSA, VRE, CDI Improved surface cleaning/disinfection reduces disease incidence MRSA, VRE, CDI

C. difficile Environmental Contamination Rutala, Weber. SHEA. 3 rd Edition Frequency of sites found contaminated~10->50% from 13 studies-stethoscopes, bed frames/rails, call buttons, sinks, hospital charts, toys, floors, windowsills, commodes, toilets, bedsheets, scales, blood pressure cuffs, phones, door handles, electronic thermometers, flow-control devices for IV catheter, feeding tube equipment, bedpan hoppers C. difficile spore load is low; 7 studies assessed the spore load and most found 100; one reported a range of “1->200” and one study sampled several sites with a sponge and found 1,300 colonies C. difficile.

FREQUENCY OF ACQUISITION OF MRSA ON GLOVED HANDS AFTER CONTACT WITH SKIN AND ENVIRONMENTAL SITES No significant difference on contamination rates of gloved hands after contact with skin or environmental surfaces (40% vs 45%; p=0.59) Stiefel U, et al. ICHE 2011;32:

Risk of Acquiring MRSA and VRE from Prior Room Occupants Admission to a room previously occupied by an MRSA-positive patient or VRE-positive patient significantly increased the odds of acquisition for MRSA and VRE (although this route is a minor contributor to overall transmission). Arch Intern Med 2006;166:1945. Prior environmental contamination, whether measured via environmental cultures or prior room occupancy by VRE-colonized patients, increases the risk of acquisition of VRE. Clin Infect Dis 2008;46:678. Prior room occupant with CDAD is a significant risk for CDAD acquisition. Shaughnessy et al. ICHE 2011;32:201

TRANSMISSION MECHANISMS INVOLVING THE SURFACE ENVIRONMENT Rutala WA, Weber DJ. In:”SHEA Practical Healthcare Epidemiology” (Lautenbach E, Woeltje KF, Malani PN, eds), 3 rd ed, 2010.

Thoroughness of Environmental Cleaning Carling et al. ECCMID, Milan, Italy, May 2011 Mean = 32% >110,000 Objects

MONITORING THE EFFECTIVENESS OF CLEANING Cooper et al. AJIC 2007;35:338 Visual assessment-not a reliable indicator of surface cleanliness ATP bioluminescence-measures organic debris (each unit has own reading scale, < RLU) Microbiological methods-<2.5CFUs/cm 2 -pass; can be costly and pathogen specific Fluorescent marker

TERMINAL ROOM CLEANING: DEMONSTRATION OF IMPROVED CLEANING l Evaluated cleaning before and after an intervention to improve cleaning l 36 US acute care hospitals l Assessed cleaning using a fluorescent dye l Interventions Increased education of environmental service workers Feedback to environmental service workers †Regularly change “dotted” items to prevent targeting objects Carling PC, et al. ICHE 2008;29:

ROOM DECONTAMINATION UNITS Rutala, Weber. ICHE. 2011;32:743

UV Room Decontamination Fully automated, self calibrates, activated by hand-held remote Room ventilation does not need to be modified Uses UV-C (254 nm range) to decontaminate surfaces Measures UV reflected from walls, ceilings, floors or other treated areas and calculates the operation time to deliver the programmed lethal dose for pathogens. UV sensors determines and targets highly-shadowed areas to deliver measured dose of UV energy (12,000µWs/cm 2 bacteria) After UV dose delivered, will power-down and audibly notify the operator Reduces colony counts of pathogens by >99.9% within 20-25m

EFFECTIVENESS OF UV ROOM DECONTAMINATION Rutala WA, et al. Infect Control Hosp Epidemiol. 2010;31:

HP SYSTEMS FOR DECONTAMINATION OF THE HOSPITAL ENVIRONMENT Falagas, et al. J Hosp Infect. 2011;78:171. Author, YearHP SystemPathogenBefore HPVAfter HPV% Reduction French, 2004VHPMRSA61/85-72%1/85-1% 98 Bates, 2005VHP Serratia 2/42-5%0/24-0%100 Jeanes, 2005VHPMRSA10/28-36%0/50-0%100 Hardy, 2007VHPMRSA7/29-24%0/29-0%100 Dryden, 2007VHPMRSA8/29-28%1/29-3% 88 Otter, 2007VHPMRSA18/30-60%1/30-3% 95 Boyce, 2008VHP C. difficile 11/43-26%0/37-0%100 Bartels, 2008HP dry mistMRSA4/14-29%0/14-0%100 Shapey, 2008HP dry mist C. difficile 48/203-24%; 77/203-3%; Barbut, 2009HP dry mist C. difficile 34/180-19%4/180-2% 88 Otter, 2010VHPGNR10/21-48%0/63-0%100

ROOM DECONTAMINATION WITH HPV l Study design Before and after study of HPV l Outcome C. difficile incidence l Results HPV decreased environmental contamination with C. difficile (p<0.001), rates on high incidence floors from 2.28 to 1.28 cases per 1,000 pt days (p=0.047), and throughout the hospital from 1.36 to 0.84 cases per 1,000 pt days (p=0.26) Boyce JM, et al. Infect Control Hosp Epidemiol. 2008;29:

UV ROOM DECONTAMINATION Rutala, Weber. ICHE. 2011;32:744

HP ROOM DECONTAMINATIION Rutala, Weber. ICHE. 2011;32:743

A Four-Arm Prospective, Multicenter Study to Assess Efficacy, Effectiveness and Feasibility of Enhanced Room Disinfection with Chlorine and UV Light Using Clinical and Microbiologic Outcomes

Rapid Hospital Room Decontamination Using UV Light With a Nanoscale Reflective Coating Assessed the time required to kill HAI pathogens in a room with standard white paint (2-5% reflective) versus walls coated with an agent formulated to be reflective to UV-C wavelengths (65% reflective) Coating uses nanoscale metal oxides whose crystal structures are reflective to UV-C Coating is white in appearance and can be applied with a brush or roller in the same way as any common interior latex paint Cost to coat walls used in this study was estimated to be <$300.

UV Reflective Coating Rutala, Gergen, Tande, Weber Line-of-SightMRSA w/coatingMRSA no coating C. difficile w/coating C. difficile no coating Cycle Time5m03s25m13s9m24s43m42s Direct4.70 (n=42)4.72 (n=33)3.28 (n=39)3.42 (n=33) Indirect4.45 (n=28)4.30 (n=27)2.42 (n=31)2.01 (n=27) Total4.60 (n=70)4.53 (n=60)2.91 (n=70)2.78 (n=60) With the nanoscale reflective coating, cycle times were 5-10m (~80% reduction) which would substantially reduce the turnover time of the room

Disinfection and Sterilization: From Benchtop to Bedside Improved products/processes/technologies  Low-temperature sterilization technology, rapid readout BIs, improved HLD/LLD, wipes, microfiber Improved knowledge  Emerging pathogens- C. difficile, Norovirus, MDROs  The role of the environment in disease transmission Guidelines/recommendations-integration of science into practice and improved patient care

Scientific Findings Incorporated Into Guidelines/Policies/Practices Guideline for Disinfection and Sterilization in Healthcare Facilities, 2008 (CDC) Multi-Society Guideline on Reprocessing Flexible Gastrointestinal Endoscopes, 2011, (ASGE, SHEA, APIC, SGNA, TJC, etc) Environmental Infection Control in Healthcare Facilities, 2003 (CDC) Disinfection and Sterilization of Prion-Contaminated Medical Instruments, 2010 (SHEA) Guideline for the Prevention and Control of Norovirus Gastroenteritis Outbreaks in Healthcare Facilities, 2011 (CDC) Clinical Practice Guideline for Clostridium difficile Infection in Adults, 2010 (SHEA, IDSA)

Summary l New sterilization, high-level disinfection and low-level disinfection technologies/practices/products are effective l New technologies/practices/products integrated into guidelines/policies/practices l Effective surface disinfection essential to eliminate the environment as a source for transmission of HA pathogens. l Room decontamination technologies should be considered for terminal room disinfection (e.g., after discharge of patients under CP, during outbreaks) if studies continue to demonstrate an infection reduction benefit.

Disinfection and Sterilization: From Benchtop to Bedside Improved products/processes/technologies  Low-temperature sterilization technology, rapid readout BIs, improved HLD/LLD, wipes, microfiber Improved knowledge  Emerging pathogens- C. difficile, Norovirus, MDROs  The role of the environment in disease transmission Guidelines-integration of science into practice and improved patient care

disinfectionandsterilization.org