Sporicides Disinfectants / Wipes do they really work? Dr Jean-Yves Maillard Welsh School of Pharmacy Cardiff University Wales

Transcription

1 Sporicides Disinfectants / Wipes do they really work? Dr Jean-Yves Maillard Welsh School of Pharmacy Cardiff University Wales

2 MICROBIAL SUSCEPTIBILITY/RESISTANCE INTRINSIC RESISTANCE TO BIOCIDES High-level Level of resistance Low-level - prions - bacterial spores - protozoal cysts - mycobacteria - naked viruses - vegetative Gram-negative - fungi - protozoa - vegetative Gram-positive - enveloped viruses SPORICIDE

3 SPORE STRUCTURE AND SUSCEPTIBILITY DEGRADATION (superoxide dismutase) EXOSPORIUM - highly reactive biocides (?) SPORE COATS - lysozymes - hypochlorites - chlorine dioxide - GTA - iodine - hydrogen peroxide - chlorhexidine - ethylene oxide (?) - ozone INACCESSIBILITY OF TARGET SITES INACCESSIBILITY OF TARGET SITES CORTEX - alkali - hypochlorites - chlorine dioxide - GTA(?) - iodine - chlorhexidine (?) - ozone (?) SPORE CORE - dehydration - SASPs (hydrogen peroxide) INACCESSIBILITY OF TARGET SITES

4 SPORULATION-GERMINATION AND ACTIVITY SPORULATION SPORICIDAL ACTIVITY SPORISTATIC ACTIVITY GERMINATION

5 SPORICIDAL AND SPORISTATIC ACTIVITIES SPORICIDAL ACTIVITY Ethylene oxide Glutaraldehyde Formaldehyde ortho-phthalaldehyde Hydrogen peroxide Peracetic acid Chlorine dioxide Ozone Sodium hypochlorite Sodium dichlororisocyanurate Chloramine-T Calcium hypochlorite Iodine and iodophors SPORISTATIC ACTIVITY Phenols and cresols Quaternary ammonium compounds Biguanides Organic acids and esters Alcohols

6 FACTORS AFFECTING SPORICIDAL ACTIVITY FACTORS IMPORTANCE FOR EFFICACY PREDICTABILITY Concentration +++ Concentration exponent ( ) Type of surface ++ Roughness Hydrophobicity Charge Porosity Organic load +++ Chemical nature of active Soiling (blood, faeces, etc.) Temperature + Q 10 ph ++ Chemical nature of active Contact time +++ Continuous release (reservoir) Relative humidity ++ Gaseous biocides Formulation ++ Depend on excipients

7 SPORICIDE EFFICACY AGAINST C. DIFFICILE Maillard J-Y. J Hosp Infect 2011; 77: BIOCIDE (spore concentration) CONCENTRATION LOG REDUCTION Glutaraldehyde TIME (min) (~10 5 ) [ Wavicide-200] ppm > Liquid hydrogen peroxide - Surface test (10 7 ) [Virox STF] ppm Liquid chlorine dioxide surface test (6 x 10 7 ) BHI growth 600 ppm 6 30 (1 x 10 7 ) CB growth 6 10 Peracetic acid suspension test (~10 5 ) [ Perasafe ] 3500 ppm (3% soiling) >4 5 Sodium dichloroisocyanurate surface test Stainless steel PVC 2600 ppm ppm <

8 SPORICIDE EFFICACY AGAINST C. DIFFICILE Maillard J-Y. J Hosp Infect 2011; 77: BIOCIDE (spore concentration) CONCENTRATION LOG REDUCTION Bleach surface test (10 7 ) [acidified bleach] (10 7 ) [regular bleach] (5 x 10 7 ) [regular bleach] 5000 ppm 1000 ppm 5000 ppm TIME (min) 3 ~25 ~10 Bleach surface test ( ) 5000 ppm 6 10 Accelerated hydrogen peroxide 4.5% 6 10

9 SPORICIDAL SPORISTATIC ACTIVITY AND CLAIM LABEL CLAIMS - wipes WIPES INGREDIENT DISCLOSED ON LABEL CLAIM ON LABEL Clinell sporicidal wipe Inorganic peroxygen generator, tetra acetyl ethylenediamine, surfactants Siani et al. AJIC 2011; 39(3): Sporicidal Trigene Advance <1% polymeric biguanide hypochloride, alkyl di-methyl benzyl ammonium chloride, didecyl dimethyl ammonium chloride Sporicidal AzoMaxActive TM QAC, PHMB and bronopol Bactericidal claim and claim against Clostridium difficile on label Sani-Cloth Rapid Activ8 TM SuperNova Tuffie Enduro Patient wipes Didecyl dimethyl ammonium chloride 0.45% Composition not disclosed; effective against C. difficile spores under 30 seconds with mechanical action of cleaning Didecyl ammonium chloride, laurakonium chloride, polyaminoporopyl biguanide, 2-bromo-2-nitro-para1-3-diol impregnated with low-level biocides 5% cationic surfactant, amphoteric surfactant and EDTA Composition not disclosed Sporicidal Sporicidal Sporicidal Sporicidal Sporicidal

10 STANDARD EFFICACY TEST PROTOCOLS PURPOSE OF EFFICACY TEST PROTOCOLS End users can select a product that is appropriate for their use - provide reliable information on the efficacy of an antimicrobial product Ensure that the product specification from the manufacturer or supplier is accurate

11 STANDARD EFFICACY TEST PROTOCOLS Most common efficacy protocols used for determining sporicidal activity against C. difficile (from label claim and web information on specific sporicidal product) Phase 1, step 1 tests: the ability of a product to demonstrate bactericidal, fungicidal or sporicidal activity, without regard to specific conditions of intended use, is tested EN14347: Basic sporicidal activity Method developed by the Horizontal Working Group Temperature: 20ºC; contact time one of the following 30, 60, 120 min; no soiling (no C. difficile) Phase 2, step 1 tests: tests are suspension tests to determine bactericidal, fungicidal, virucidal or sporicidal activity under laboratory conditions that simulate practical conditions. EN1276: Bactericidal suspension test (no C. difficile) Method developed by the Food Hygiene and Domestic and Institutional use Working Group Temperature: 20ºC(4-40ºC); contact time: 5 min (1-60 min) EN13704: Sporicidal suspension test (no C. difficile) Method developed by the Food Hygiene and Domestic and Institutional use Working Group Temperature: 20ºC(4-40ºC); contact time: 5 min (1-60 min)

12 INTERPRETING EFFICACY TEST PROTOCOLS PRODUCT A Sporicidal, kill Clostridium difficile (C.diff) spores (EN 1276 & EN 14347), started with 15,300,000 c. diff spores and were reduced in one minute contact time to less than 10 C. diff spores in both clean & dirty conditions EN1276 Bactericidal NOT sporicidal EN14347 BASIC sporicidal test NO soiling PRODUCT B EN 1276: Campylobacter jejuni, E. coli, E. hirae, Klebsiella pneumoniae, Listeria monocytogenes, MRSA, Mycobacterium avium, Pseudomonas aeruginosa, Proteus vulgaris, Vibrio cholerae and Clostridium difficile (spores & vegetative)

13 INTERPRETING EFFICACY TEST PROTOCOLS PRODUCT C Product C achieved a 100% kill of vegetative cells of Clostridium difficile ATCC 9689 (1.1 x 10 7 ) dried out on a 12 inch square stainless steel test surface. (Wipe time: 30 seconds) Validation of Product C efficacy against Clostridium difficile ATCC 9689 surface test Methodology: The test organism was inoculated into 9ml of cooked meat medium (Biomerieux) and incubated at 37 0 C for 48 hours to obtain a culture containing approximately 10 8 cells/ml (actual count = 1.1 x 10 8 /ml). A 12 inch square test surface was marked out on a stainless steel plate and one ml of inoculum was spread over the test surface and allowed to dry for 30 minutes. The Product C was wiped systematically over the test surface for 30 seconds. Suspensions were taken from the surface of the test site and from the wipe itself, plated out on HBA plates and incubated in an anaerobic jar for five days at 37 o C. NO MENTION THAT THE TEST WAS CONDUCTED ANAEROBICALLY!!

14 TESTING SPORICIDAL WIPES ACTIVITY ROLE OF WIPES Remove bioburden from a surface Prevent transfer of bioburden from the wipe to other surfaces Where antimicrobial is present kill the microbial bioburden LIMITATIONS OF WIPES Test protocol to evaluate activity Qualitative agar diffusion test (ISO 20645) CONTROL TEST good antimicrobial effect (test interpretation) Antimicrobial activity: inhibitory or lethal effect from active released in the agar

15 TESTING SPORICIDAL WIPES ACTIVITY Antimicrobial wipe usage Williams et al. J Hosp Infect 2007; 67: Wipe Number Surface initially wiped Time applied (seconds) Number of consecutive surfaces wiped (other surfaces) 1 Bed Rail 4 5 (bedside table, monitor X2, monitor stand) 2 Steel Trolley 6 2 (both shelves on the trolley wiped) 1 Monitor 4 5 (monitors, two keypads, monitor stand) 2 Bed rail 7 4 (table, monitor, keypad) 3 Bedside table 10 4 (folder, two bed rails)

16 TESTING SPORICIDAL WIPES ACTIVITY Efficacy of antimicrobial wipes: Quantitative three stage test Williams et al. J Hosp Infect 2007;67: Observation of usage in practice cleaning staff in ITUs - use of wipes surface area - contact - rotation Stage 1 bacterial removal How good are the wipes in removing microbial contaminants? (not killing effect) Stage 2 bacterial transfer adpression tests Can the wipes transfer survivors to other surfaces (i.e. crosscontaminate)? Stage 3 Antimicrobial activity Can the wipes kill the bacteria they remove?

17 TESTING SPORICIDAL WIPES ACTIVITY SPORICIDAL EFFICACY efficacy testing against C. difficile NCTC12727 Wipes Bacterial Removal (log 10 cfu/disk ± SD) 500 g surface pressure Bacterial transfer following 10 s wiping time at 500 g surface pressure Negative control 1.13 (± 0.36) 5 consecutive transfers. TNTC Hypochlorite soaked wipe 2.02 (± 0.21) 5 consecutive transfers. TNTC Clinell sporicidal wipe 4.09 (± 0.79) No spore transferred TriGene Advance 0.22 (± 0.07) 5 consecutive transfers. From 0 to TNTC AzoMaxActive TM 1.30 (± 0.33) 5 consecutive transfers. From 0 to TNTC Sani-Cloth Rapid 0.57 (± 0.07) 5 consecutive transfers. From 1 to TNTC Activ8 TM (± 0.08) 5 consecutive transfers. TNTC Siani et al. AJIC 2011; 39(3): SuperNova 1.14 (± 0.65) 5 consecutive transfers. From 83 to TNTC Tuffie 0.67 (± 0.11) 5 consecutive transfers of 43 bacteria Enduro Patient wipes 0.88 (± 0.13) 5 consecutive transfers. From 2 to TNTC NewGenn 0.84 (± 0.66) 5 consecutive transfers. From 40 to TNTC

18 TESTING SPORICIDAL WIPES ACTIVITY SPORICIDAL EFFICACY efficacy testing against C. difficile NCTC12727 Wipes Claim on label Sporicidal effect (log 10 reduction ±SD) Clinell sporicidal wipe 10 s contact time 5 min contact time Sporicidal 0.11 Sporicidal (± 0.15) 1.54 (± 0.84) TriGene Advance Sporicidal 0.04 (± 0.05) (± 0.03) AzoMaxActive TM Bactericidal claim and claim against Clostridium difficile on label 1.41 (± 0.14) (± 0.15) Sani-Cloth Rapid Sporicidal 1.77 (± 0.27) 0.01 (± 0.44) Activ8 TM Sporicidal Sporistatic 0.99 (± 0.14) (± 0.15) SuperNova Sporicidal 1.96 (± 0.09) (± 0.13) Tuffie Sporicidal 0.37 (± 0.23) (± 0.19) Enduro Patient wipes Sporicidal 0.41 (± 0.10) (± 0.10) NewGenn No sporicidal claim on label 0.31 (± 0.15) (± 0.14) Hypochlorite soaked wipe Siani et al. AJIC 2011; 39(3): ppm Sporicidal (± 0.49) 5.39 (± 0.00)

19 TESTING SPORICIDAL WIPES ACTIVITY SPORE ASSOCIATION WITH WIPE MATERIALS Siani et al. AJIC 2011; 39(3): Electron micrographs of inoculated with C. difficile R20291 ribotype 027 Clinell sporicidal wipe TriGene Advance Tuffie Control Inoculated

20 SPORICIDE EFFICACY AGAINST C. DIFFICILE Biocides efficacy against the transmission of C. difficile Sporicidal test: suspension test Murine model disinfection of cages (15 ml for 10 min) Lawley et al. Appl Environ Microbiol 2010; 76: BIOCIDES COMPOSITION LOG REDUCTION TRANSMISSION 70% ethanol Alcohol <1 High HiBi Scrub Chlorhexidine digluconate <1 High Flash Benzisothiazolinone 1 High Steri-7 Isothiazolin-benzalkonium chloride 1 High Virusolve Alkyl triamine/bromine 4 Low Chlor-clean Sodium dichloroisocyanurate > 5 nill Hydrogen peroxide vapour Hydrogen peroxide vapour (400 ppm 1 min) - nill

21 SPORICIDES AND SURFACE DISINFECTION IN SITU ALCOHOL-BASED HAND RUBS Hsu et al. Am J Gastroenterol 2010;105: TRIAL STUDY DESIGN POPULATION RESULTS Pre-intervention Post-intervention Gopal Rao et al. J Hosp Infect 2002; 50:42-7 Gordin et al. Infect Control hosp Epidemiol 2005; 26:650-3 Interventional before-after non randomized historical control Interventional before-after non randomized historical control Patients hospital wide (ages not specified) Adult patients hospital wide 11.5 cases per 1000 admissions 3.24 cases per patient care days 9.5 cases per 1000 admissions (P=0.02) 3.38 cases per patient care days (P=0.78)

22 SPORICIDES AND SURFACE DISINFECTION IN SITU HYPOCHLORITE DISINFECTANTS Hsu et al. Am J Gastroenterol 2010;105: TRIAL STUDY DESIGN POPULATION RESULTS Pre-intervention Post-intervention Mayfield et al. Clin Infect Dis 2000; 31: Wilcox et al. J Hosp Infect 2003:54: McMullen et al. Infect Control Hosp Epidemiol 2007; 28:205-7 Interventional beforeafter; historical control Non randomized cross-over control Interventional beforeafter; Outbreak Adult patients in the bone marrow transplant unit, the neurosurgical intensive care unit and a general medicine unit Elderly patients on two elected medicine wards Medical and surgical intensive care units 8.6 cases per 1000 patient days 8.9 cases per 100 admissions MICU: 16.6 cases per 1000 patient days SICU: 10.4 cases per 1000 patient days 3.3 cases per 1000 patient days 5.3 cases per 100 admissions (P<0.05) (decline only in one unit) MICU: 3.7 cases per 1000 patient days SICU: 3.9 cases per 1000 patient days

23 SPORICIDES AND SURFACE DISINFECTION IN SITU HYDROGEN PEROXIDE VAPOUR Hsu et al. Am J Gastroenterol 2010;105: TRIAL STUDY DESIGN POPULATION RESULTS Boyce et al. Infect Control Hosp Epidemiol 2008; 29:723-9 Prospective interventional before-after Five inpatient units All room vacated by patients Pre-intervention 2.28 cases per 1000 patient days 1.89 cases per 1000 patient days Postintervention 1.28 cases per 1000 patient days (P=0.047) 0.88 cases per 1000 patient days (P=0.047)

24 SURFACE DISINFECTION AND SPORICIDES SURFACE DISINFECTION WITH LIQUID SPORICIDES HIGH CONCENTRATION LONG CONTACT TIME (5-10 min) LOW CONCENTRATION SHORT CONTACT TIME (< 5 min) USE OF SPORISTATIC BIOCIDE INAPPROPRIATE EFFICACY TEST PROTOCOL In vitro - in situ FAILURE OF SPORICIDE - spore survival - spore persistence SPORICIDAL WIPES -removing bioburden -killing spores (in the wipe) NEED OF ADDITIONAL CONTROL MEASURES

25 SURFACE DISINFECTION AND SPORICIDES Ensuring efficacy of sporicidal activity EFFICACY Clear understanding of the product limitations Clear understanding of the factors affecting activity Clear understanding of product application Clear manufacturer s instructions including limitations of the products Ease of use (e.g. avoiding dilution / appropriate dispenser) KNOWLEDGE Efficacy test protocols Matching product and application

26 SURFACE DISINFECTION AND SPORICIDES ARHAI/HIS task force on sporicidal disinfectants Wilcox et al. J Hosp Infect 2011; 77: A taskforce has now been formed with representatives from the Department of Health's Advisory Committee on Antimicrobial Resistance and Healthcare Associated Infection (ARHAI), the Hospital Infection Society (HIS) HIS, the Department of Health (England) and the Health Protection Agency. AIMS: 1.to develop an accepted standard for laboratory testing of disinfectants which claim to have activity against C. difficile spores; 2.to develop a network of laboratories with capability to perform in vitro assays of sporicidal activity of disinfectants 3.to explore the creation of a national quality assessment scheme for laboratories which perform in vitro assays of sporicidal activity of disinfectants.

27 SURFACE DISINFECTION AND WIPES

28 THANK YOU Sporicidal wipes - Harsha Siani - Callum Cooper Lovleen Joshi