# Presentation: 502771

## CJD: Recommendations for Disinfection and Sterilization in Health Care

- William A. Rutala, Ph.D., M.P.H.
- University of North Carolina (UNC) Hospitals and UNC School of Medicine

## CJD: Disinfection and Sterilization Topics

- Rationale for US recommendations
- Epidemiological studies of prion transmission
- Infectivity of human tissues
- Efficacy of removing microbes by cleaning
- Prion inactivation studies
- Recommendations to prevent cross-transmission from medical devices contaminated with prions
- Methodology-how methodology affects results

## CJD: DISINFECTION AND STERILIZATION

- Rationale for US recommendations
- Epidemiological studies of prion transmission
- Epidemiological studies of prion transmission via surgical instruments
- Infectivity of human tissues
- Efficacy of removing microbes by cleaning
- Prion inactivation studies
- Risk associated with instruments

## Transmissibility of Prions

- Transmission
- Not spread by contact (direct, indirect, droplet) or airborne
- Not spread by the environment
- Experimentally-all TSEs are transmissible to animals, including the inherited forms
- Epidemiology of CJD: sporadic-85%; familial-15%; iatrogenic-1% (primarily transplant of high risk tissues, ~250 cases worldwide)

## Iatrogenic Transmission of CJD

- Contaminated medical instruments
- Electrodes in brain (2)
- Neurosurgical instruments in brain (4)
- Dura mater grafts (>110)
- Corneal grafts (3)
- Human growth hormone and gonadotropin (>130)

## CJD: DISINFECTION AND STERILIZATION

- Rationale for US recommendations
- Epidemiological studies of prion transmission
- Epidemiological studies of prion transmission via surgical instruments
- Infectivity of human tissues
- Efficacy of removing microbes by cleaning
- Prion inactivation studies
- Risk associated with instruments

## CJD and Medical Devices

- Six cases of CJD associated with medical devices
- 2 confirmed cases-depth electrodes; reprocessed by benzene, alcohol and formaldehyde vapor
- 4 cases-CJD following brain surgery, index CJD identified-1, suspect neurosurgical instruments
- Cases occurred before 1980 in Europe
- No known cases since 1980 and no known failure of steam sterilization

## CJD: DISINFECTION AND STERILIZATION

- Rationale for US recommendations
- Epidemiological studies of prion transmission
- Epidemiological studies of prion transmission via surgical instruments
- Infectivity of human tissues
- Efficacy of removing microbes by cleaning
- Prion inactivation studies
- Risk associated with instruments

## Risk of CJD Transmission

- Epidemiologic evidence (eye, brain) linking specific body tissue or fluids to CJD transmission
- Experimental evidence in animals demonstrating that body tissues or fluids transmit CJD
- Infectivity assays a function of the relative concentration of CJD tissue or fluid

## Risk of CJD Transmission

| Risk of Infection | Tissue |
| --- | --- |
| High | Brain (including dura mater), spinal cord, and eye |
| Low | CSF, liver, lymph node, kidney, lung, spleen, placenta, olfactory epithelium |
| No | Peripheral nerve, intestine, bone marrow, whole blood, leukocytes, serum, thyroid gland, adrenal gland, heart, skeletal muscle, adipose tissue, gingiva, prostate, testis, tears, nasal mucus, saliva, sputum, urine, feces, semen, vaginal secretions, and milk |

- High-transmission to inoc animals >50%; Low-transmission to inoc animals >10-20% but no epid evidence of human inf

## CJD: DISINFECTION AND STERILIZATION

- Rationale for US recommendations
- Epidemiological studies of prion transmission
- Epidemiological studies of prion transmission via surgical instruments
- Infectivity of human tissues
- Efficacy of removing microbes by cleaning
- Prion inactivation studies
- Risk associated with instruments

## CJD: DISINFECTION AND STERILIZATION

- Effectiveness must consider both removal by cleaning and inactivation
- Probability of a device remaining capable of transmitting disease depends on the initial contamination and effectiveness of C/D/S.
- Cleaning results in a 4 log10 reduction of microbes and ~2 log10 reduction in protein contamination

## CJD: DISINFECTION AND STERILIZATION

- Rationale for US recommendations
- Epidemiological studies of prion transmission
- Epidemiological studies of prion transmission via surgical instruments
- Infectivity of human tissues
- Efficacy of removing microbes by cleaning
- Prion inactivation studies
- Risk associated with instruments

## Decreasing Order of Resistance of Microorganisms to Disinfectants/Sterilants

- Prions
- Spores
- Mycobacteria
- Non-Enveloped Viruses
- Fungi
- Bacteria
- Enveloped Viruses

## Ineffective or Partially-Effective Disinfectants:CJD

- Alcohol
- Ammonia
- Chlorine dioxide
- Formalin
- Glutaraldehyde
- Hydrogen peroxide
- Iodophors/Iodine
- Peracetic acid
- Phenolics

## Ineffective or Partially Effective Processes: CJD

- Gases
- Ethylene oxide
- Formaldehyde
- Physical
- Dry heat
- UV
- Microwave
- Ionizing
- Glass bead sterilizers
- Autoclave at 121oC, 15m

## Effective Disinfectants(>4 log10 decrease in LD50  with 1 hour)

- Sodium hydroxide
- 1 N for 1h (variable results)
- Sodium hypochorite
- 5000 ppm for 15m
- Guanidine thiocyanate
- 4M
- Phenolic (LpH)
- 0.9% for 30m

## Effective Processes: CJD

- Autoclave
- 134oC-138oC for 18m (prevacuum)
- 132oC for 60m (gravity)
- Combination (chemical exposure then steam autoclave, potentially deleterious to staff, instruments, sterilizer)
- Soak in 1N NaOH, autoclave 134oC for 18m
- Soak in 1N NaOH, autoclave 121oC  for 30m

## CJD: DISINFECTION AND STERILIZATION

- Rationale for US recommendations
- Epidemiological studies of prion transmission
- Epidemiological studies of prion transmission via surgical instruments
- Infectivity of human tissues
- Efficacy of removing microbes by cleaning
- Prion inactivation studies
- Risk associated with instruments

## Disinfection and Sterilization

- EH Spaulding believed how an object will be D/S depended on the objects intended use
- CRITICAL-objects that enter normally sterile tissue or the vascular system should be sterile
- SEMICRITICAL-objects that touch mucous membranes or skin that is not intact requires a disinfection process (high level disinfection) that kills all but bacterial spores (prions?)
- NONCRITICAL-objects that touch only intact skin require low-level disinfection

## CJD : potential for secondary

- spread through contaminated
- surgical instruments

## Risk Assessment: Patient, Tissue, Device

- Patient
- Known or suspected CJD or other TSEs
- Rapidly progressive dementia
- Dura mater transplant, HGH injection
- Tissue
- High risk-brain,  spinal cord, eyes
- Device
- Critical or semicritical

## Examples: CJD D/S

- High risk patient, high risk tissue, critical/semicritical device-special prion reprocessing
- High risk patient, **low/no risk tissue**, critical/semicritical device-conventional D/S
**Low risk patient**, high risk tissue, critical/semicritical device-conventional D/S
- High risk patient, high risk tissue, **noncritical device**-conventional disinfection

## Conclusions

- Epidemiologic evidence suggests nosocomial CJD transmission via medical devices is very rare
- Guidelines based on epidemiologic evidence, tissue infectivity, risk of disease via medical devices, and inactivation data
- Risk assessment based on patient, tissue and device
- Only critical/semicritical devices contacting high risk tissue from high risk patients require special prion reprocessing

## CJD: Disinfection and Sterilization Conclusions

- Cleaning with special prion reprocessing
- NaOH and steam sterilization (e.g., 1N NaOH 1h, 121oC 30 m)
- 134oC for 18m (prevacuum)
- 132oC for 60m (gravity)
- No low temperature sterilization technology effective
- Four disinfectants (e.g., chlorine) effective (4 log decrease in LD50 within 1h)

## CJD: Sterilization in Health Care

- Used Instrument
- 
- Keep Wet (do not let tissue/fluid dry)
- 
- Clean (Washer Disinfector)
- 
- Steam Sterilize (NaOH and SS; 134oC, 18 min)
- 
- Sterile Instrument

## CJD: Environmental Surfaces

- High/Low/No Risk Tissue, High Risk Patient, **Noncritical Surface/Device**
- Environmental surfaces contaminated with high risk tissues (autopsy table in contact with brain tissue) should be cleaned and then spot decontaminated with a 1:10 dilution of bleach
- Environmental surfaces contaminated with low/no risk tissue require only routine disinfection

## CJD: Disinfection and Sterilization Topics

- Rationale for US recommendations
- Epidemiological studies of prion transmission
- Infectivity of human tissues
- Efficacy of removing microbes by cleaning
- Prion inactivation studies
- Recommendations to prevent cross-transmission from medical devices contaminated with prions
- Methodology-how methodology affects results

## Decreasing Order of Resistance of Microorganisms to Disinfectants/Sterilants

- Prions
- Spores
- Mycobacteria
- Non-Enveloped Viruses
- Fungi
- Bacteria
- Enveloped Viruses

## Prion Inactivation Studies

- Problems
- Investigators used aliquots of brain tissue macerates vs. intact tissue (smearing, drying); weights of tissue (50mg-375mg)
- Studies do not reflect reprocessing procedures in a clinical setting (e.g., no cleaning)
- Factors that affect results include: strain of prion (22A), prion conc in brain tissue, animal used, exposure conditions, validation and cycle parameters of sterilizers, resistant subpopulation, different test tissues, different duration of observations, screw cap tubes with tissue (air), etc

## STERILIZATION

**Factors affecting the efficacy of sterilization**
- Bioburden
- Cleaning
- Pathogen type
- Protein and salt
- Biofilm accumulation
- Lumen length and diameter
- Restricted flow

## Slide 32

## Slide 33

## Penicylinders Sterilized by Various Low-Temperature Sterilization Methods

- Challenge:	12/88		100%ETO	HCFC-ETO	Sterrad
- 10% Serum,
- 0.65% Salt
- (7 organisms, N=63)		97%	   60.3%		95.2%		37%
- No Serum or Salt,
- (3 organisms, N=27)		100%		100%		96%		100%
- Alfa et al. Infect Cont Hosp Epidemiol 1996;17:92-100. The three organisms included: *E. faecalis*, *M. chelonei, B. subtilis* spores. The seven organisms included: *E. faecalis*, *P. aeruginosa, E.coli*, *M. chelonei, B. subtilis* spores, *B. stearothermophilus* spores, *B. circulans* spores

## Slide 35

## Lumens Sterilized by VariousLow-Temperature Sterilization Methods

- Challenge:	12/88		100%ETO	HCFC-ETO	Sterrad
- 10% Serum,
- 0.65% Salt
- (7 organisms, N=63)		44%		39.7%		49.2%		35%
- No Serum or Salt,
- (3 organisms, N=27)		ND		96.3%		96.3%		ND
- Alfa et al. Infect Cont Hosp Epidemiol 1996;17:92-100. The three organisms included: *E. faecalis*, *M. chelonei, B. subtilis* spores. The seven organisms included: *E. faecalis*, *P. aeruginosa, E.coli*, *M. chelonei, B. subtilis* spores, *B. stearothermophilus* spores, *B. circulans* spores

## Low-Temperature Sterilization Technologies (LTST)Conclusions

- All technologies have limitations
- LTST (ETO, HP gas plasma) demonstrate a significant number of failures in presence of serum or salt
- Salt and serum provide protection for spores and bacteria
- Salt and serum combined with a narrow lumen provide extraordinary protection with LTST

## STERILIZATION

**Factors affecting the efficacy of sterilization**
- Bioburden
- Cleaning
- Pathogen type
- Protein and salt
- Biofilm accumulation
- Lumen length and diameter
- Restricted flow

## Effect of Rinsing with Water on Sterilization Results

- Method
- Inoculate scalpel blade with tissue culture media with 10% fetal bovine serum containing 1.5x106 *Geobacillus stearothermophilus* spores dried for 12 hours at room temperature

## Slide 40

## Slide 41

## Slide 42

## Slide 43

## Slide 44

## Removal of Soil and Microorganisms from Medical Devices

- Method
- Inoculate 0.02 ml of FBS containing 106 *B. stearothermophilus* spores onto scalpel blade
- Dry for 30 min at 35oC followed by 30 min at RT
- Samples placed in distilled water at room temperature for specified time
- Chloride, protein and spore concentration measured

## Slide 46

## Removal of Soil and Microorganisms from Medical DevicesConclusions

- Inorganic, organic and microbial contaminants on a device are dramatically reduced during a washing process
- 96.3% (or 2.5 x 106 organisms) removed from blade in 150 sec

## Slide 48

## Removal of Soil and Microorganisms from Medical DevicesConclusions

- Inorganic, organic and microbial contaminants on a device are dramatically reduced during a washing process
- Contact with water for short period of time rapidly leads to the dissolution of salt crystals. Studies in 1950’s and 1960’s show that spores occluded inside crystals were very resistant to sterilization (e.g., ETO, steam).
- Minimal cleaning eliminates the effect of salt
- Simulated use tests that do not include washing would not represent conditions that exist in use situation

## Slide 50

- You can clean
- without sterilization
- but you NEVER
- can sterilize
- without cleaning

## Conclusions

- All sterilization processes effective in killing spores
- Salt favors crystal formation and impairs sterilization by occlusion of organisms
- Cleaning removes salts and proteins and must precede sterilization
- Failure to clean or ensure exposure of microorganisms to sterilant (e.g. connectors) could affect effectiveness of sterilization process
- CJD inactivation studies should be consistent with actual clinical practice

## CJD: Disinfection and Sterilization Topics

- Rationale for US recommendations
- Epidemiological studies of prion transmission
- Infectivity of human tissues
- Efficacy of removing microbes by cleaning
- Prion inactivation studies
- Recommendations to prevent cross-transmission from medical devices contaminated with prions
- Methodology-how methodology affects results

**Thank you**

## References

- Alfa MJ, Olson N, DeGagne P, Hizon R.  New low temperature sterilization technologies: Microbicidal activity and clinical efficiency.  In Rutala WA, ed. *Disinfection, Sterilization, and Antisepsis in Healthcare*. Champlain, NY: Polyscience Publications. 1998:67-78.
- Rutala WA, Weber DJ. Clinical effectiveness of low-temperature sterilization technologies. Infect Control Hosp Epidemiol 1998;19:798-804.
- Jacobs P. Cleaning: principles and benefits. In: Rutala WA, ed. *Disinfection, Sterilization, and Antisepsis in Healthcare*.  Champlain, NY: Polyscience Publications. 1998:165-182.

## Disinfection and Sterilization for Prion DiseasesReferences

- Rutala WA, Weber DJ. Creutzfeldt-Jakob Disease: Recommendations for Disinfection and Sterilization. Clin Inf Dis 2001;32:1348-1356.
- Rutala WA, Weber DJ, and HICPAC. CDC Guideline for Disinfection and Sterilization. In preparation
- Weber DJ, Rutala WA. Managing the risks of nosocomial transmission of prion diseases. Current Opinions in Infectious Diseases. 2002;15:421-426.

## Prevent Patient Exposure to CJD Contaminated Instruments

- How do you prevent patient exposure to neurosurgical instruments from a patient who is latter given a diagnosis of CJD?
- Hospitals should use the special prion reprocessing precautions for instruments from patients undergoing brain biopsy when a specific lesion has not been demonstrated (e.g., CT, MRI). Alternatively, neurosurgical instruments used in such cases could be disposable.

## vCJD: Disinfection and Sterilization

- To date no reports of human-to-human transmission of vCJD by blood or tissue
- Unlike CJD, vCJD detectable in lymphoid tissues and prior to onset of clinical illness
- Special prion reprocessing (or single use instruments) proposed in the UK in dental, eye, or tonsillar surgery on high risk patients for CJD or vCJD
- If epidemiological and infectivity data show these tissues represent a transmission risk then special prion reprocessing could be extended to these procedure

## Factors Affecting the Efficacy of LTST

- Cleaning - Failure to clean results in higher bioburden, protein load and salt concentration
- Bioburden - Natural bioburden on surgical devices 100 to 103
- Pathogen - Spore forming organisms most resistant
- Protein - Residual protein decreases efficacy of sterilization
- Salt - Residual salt decreases efficacy of sterilization