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Transcript
Chemical Disinfection
衛生署 疾病管制局
中區傳染病防治醫療網
王任賢 指揮官
Chemicals
n
n
Use depends on
spectrum of
antimicrobial activity
and compatibility
with materials
Also limited by
dangers of
chemicals
themselves
n
Examples
n
n
n
n
n
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n
Halogens
Alcohols
Alkylating agents
Ethylene oxide
Phenolics
cetrimide (QAC)
chlorhexidine
(diguanide)
The Ideal Disinfectant
Ø Resistant to inactviation
Ø Broadly active (killing pathogens)
Ø Not poisonous (or otherwise harmful)
Ø Penetrating (to pathogens)
Ø Not damaging to non-living materials
Ø Stable
Ø Easy to work with
Ø Otherwise not unpleasant
Disinfectant殺菌效果之決定因素
Ø Disinfectant concentrations
Ø Length (time) of administration
Ø Temperature during administration (usual chemical reaction
2x increase in rate with each 10°C increase in temperature)
Ø Microbe type (e.g., mycobacteria, spores, and certain viruses
can be very resistant to disinfection—in general vegetative
cells in log phase are easiest to kill)
Ø Substrate effects (e.g., high organic content interferes with
disinfection—stainless steel bench easier to disinfect than
turd)
Ø It is easier (and faster) to kill fewer microbes than many
microbes
Factors determining usefulness
of chemical disinfection
n
Spectrum of antimicrobial activity
n
n
is it the right agent for the job?
Used at correct concentration
n
n
n
n
concept of 'in use concentration’
diluted down from high concentration
stored for <24 hours
no topping up of old solutions
Factors determining usefulness
of chemical disinfection
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Time of exposure
n
n
n
Correct pH?
Inactivating materials
n
n
You cannot disinfect an endoscope in 5
minutes glutaraldehyde!
Pus, blood vomit, cork, soaps etc
Is disinfectant sterile?
n
n
Many cases of Gram-negatives living in
disinfectants!
Microbiological “in-use” testing
Agent
Mechanisms of Action
Comments
Moist Heat, boiling
Denatures proteins
Kills vegetative bacterial cells and
viruses Endospores survive
Moist Heat,
Autoclaving
Denatures proteins
121°C at 15 p.s.i. for 30 min kills
everything
Moist Heat,
Pasteurization
Denatures proteins
Kills pathogens in food products
Dry Heat, Flaming
Incineration of contaminants
Used for inoculating loop
Dry Heat, Hot air
oven
Oxidation & Denatures
proteins
170°C for 2 hours; Used for glassware &
instrument sterilization
Filtration
Separation of bacteria from
liquid (HEPA: from air)
Used for heat sensitive liquids
Cold, Lyophilization
(also desiccation)
Desiccation and low
temperature
Used for food & drug preservation; Does
not necessarily kill so used for Long-term
storage of bacterial cultures
Cold, Refrigeration
Decreased chemical reaction
rate
Bacteriostatic
Osmotic Pressure,
Addition of salt or
sugar
Plasmolysis of contaminants
Used in food preservation (less effective
against fungi)
Radiation, UV
DNA damage (thymine dimers)
Limited penetration
Radiation, X-rays
DNA damage
Used for sterilizing medical supplies
Strong vis. Light
Line-drying laundry
Agent
Mechanisms of Action
Comments
Surfactants
Membrane Disruption;
increased penetration
Soaps; detergents
Quats (cationic
detergent)
Denature proteins; Disrupts
lipids
Antiseptic - benzalconium chloride,
Cepacol; Disinfectant
Organic acids and
bases
High/low pH
Mold and Fungi inhibitors; e.g.,
benzoate of soda
Heavy Metals
Denature protein
Antiseptic & Disinfectant; Silver Nitrate
Halogens
Oxidizing agent
Disrupts cell membrane
Antiseptic - Iodine (Betadine)
Disinfectant - Chlorine (Chlorox)
Alcohols
Denatures proteins;
Disrupts lipids
Antiseptic & Disinfectant
Ethanol and isopropyl
Phenolics
Disrupts cell membrane
Disinfectant, Irritating odor
Aldehydes
Denature proteins
Gluteraldehyde - disinfectant (Cidex);
Formaldehyde - disinfectant
Ethylene Oxide
Denaturing proteins
Used in a closed chamber to sterilize
Oxidizing agents
Denature proteins
Hydrogen peroxide – antiseptic;
Hydrogen peroxide – disinfectan;
Benzoyl peroxide – antiseptic
Selection criteria
(chemical antimicrobial agents)
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Antimicrobial efficacy
Corrosivity
Chemical hazard
Environmental concerns
Use solution pH
Stability
Biocidal spectrum
Corrosivity
Chemical hazard
Environmental concerns
Stability
Surfactants
Soap and Detergents
n
n
n
n
Soaps are sodium or potassium salts of fatty
acids, a natural product
Detergents, instead, are artificial surfactants
While soaps are always negatively charged,
some detergents are negatively charged
while others are positively charged
One example of a positively charged
detergent are quaternary ammonium
compounds (a.k.a., quats)
Chlorhexidine (a diguanide)
n
n
n
Used as general purpose
antiseptic for skin and
mucous membranes in
many formulations, e.g.
Hibiscrub, Hibisol, Savlon
Advantages: relatively
non-toxic and good
against S. aureus
Disadvantages: can
support growth of e.g. P.
aeruginosa
Phenolics & QACs
n
n
n
Clear soluble phenolics (e.g. Hycolin) used
as disinfectant on soiled surfaces, relatively
inactive against spores and viruses
Hexachlorophane used as surgical scrub
Quaternary ammonium compounds, e.g.
cetrimide usually only used in combination
with other agents; good detergent
properties.
Phenols and Phenolics
u
Phenol (carbolic acid) was first used by Lister as a
disinfectant.
u
u
u
u
Phenolics are chemical derivatives of phenol
u
u
u
u
Rarely used today because it is a skin irritant and has strong
odor.
Used in some throat sprays and lozenges (錠劑).
Acts as local anesthetic.
Cresols: Derived from coal tar (Lysol).
Biphenols (pHisoHex): Effective against gram-positive
staphylococci and streptococci. Used in nurseries. Excessive
use in infants may cause neurological damage.
Destroy plasma membranes and denature proteins.
Advantages: Stable, persist for long times after applied,
and remain active in the presence of organic compounds.
Phenol, Carbolic Acid, & Phenolics
n
n
n
n
n
n
Phenol (carbolic acid) and derivatives
Affect plasma membrane, inactivates enzymes, and
denature proteins
Stable, persistant, and especially effective when
dealing with disinfecting materials contaminated with
organics…
… but leave residual films, can irritate skin, don’t kill
endospores, and are corrosive to rubber and plastics
Some phenolics are mild enough for use as
antiseptics while others are too harsh or otherwise
dangerous to be employed on living tissue
Hexachlorophene, Triclosan, Lysol, soap
Quaternary Ammonium
Compounds (Quats)
u
u
u
u
u
u
u
u
Widely used surface active agents.
Cationic (positively charge) detergents.
Effective against gram positive bacteria, less effective
against gram-negative bacteria.
Also destroy fungi, amoebas, and enveloped viruses.
Zephiran, Cepacol, also found in our lab spray bottles.
Pseudomonas strains that are resistant and can grow
in presence of Quats are a big concern in hospitals.
Advantages: Strong antimicrobial action, colorless,
odorless, tasteless, stable, and nontoxic.
Diasadvantages: Form foam. Organic matter
interferes with effectiveness. Neutralized by soaps
and anionic detergents.
Quats
Ø Quats are cationic detergents that act by disrupting lipid
bilayers
Ø Quats are bactericidal, fungicidal, viricidal (enveloped),
and amoebicidal
Ø Quats are most effective against Gram-positive bacteria
Ø Quats do not kill endospores, Mycobacteria spp., nor
non-enveloped viruses
Ø Quats are rapidly inactivated by organics including
cotton and soap
Ø Zephiran à Benzalkonium chloride
Ø Cepacol àCetylpyridinium chloride
Halogens
n
n
Hypochlorites
(household bleach) &
chlorine
Advantages
n
n
active against viruses,
spores, fungi
Disadvantages
n
inactivated by organic
matter, freshness & pH
critical (go off if diluted),
corrosive to metals
n
Practical Uses
n
n
n
n
0.1% hypochlorite used as
general disinfectant
Strong hypochlorite (0.25%)
used in lab & on wounds
Extra strong (1%) used on
HBV blood spills
Chlorine used to treat
drinking water and control
Legionella
Halogens
n
n
n
n
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n
Two halogens are regularly employed as
antimicrobials: Iodine and Chloride
Iodine: commonly used as an antiseptic against all
microbes, fungi, and viruses
Iodine: It inhibits protein synthesis and oxidizes –SH
groups of amino acids
Chlorine: Used as a disinfectant (10% bleach)
Chlorine: Hypochlorous acid (HOCl) is a product,
formed in water, that is the active form of the
disinfectant
Chlorine: Applied in treatment of drinking water,
swimming pool, and sewage
Halogens
n
n
Iodophors & iodine
Advantages
n
n
Disadvantages
n
n
Some activity against viruses, spores, fungi
inactivated by organic matter, can stain skin,
irritant, expensive
Practical Uses
n
n
Pre-op skin disinfection
Povidone iodine used as surgical scrub, as
powder on ulcers
Halogens
Effective alone or in compounds
A. Iodine:
u Tincture of iodine (alcohol solution) was one of first
antiseptics used.
u Combines with amino acid tyrosine in proteins and
denatures proteins.
u Stains skin and clothes, somewhat irritating.
u Iodophors: Compounds with iodine that are slow
releasing, take several minutes to act. Used as skin
antiseptic in surgery. Not effective against bacterial
endospores.
u Betadine
u Isodine
Halogens
Effective alone or in compounds
B. Chlorine:
u When mixed in water forms hypochlorous acid:
Cl2 + H2O ------>
H+
+ Cl- + HOCl
Hypochlorous acid
u
u
u
u
Used to disinfect drinking water, pools, and sewage.
Chlorine is easily inactivated by organic materials.
Sodium hypochlorite (NaOCl): Is active ingredient
of bleach.
Chloramines: Consist of chlorine and ammonia.
Less effective as germicides
Chlorination
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1744 discovered in Sweden
1810 identified as an element
1835 first used to control odors
1890’s started to be used as a disinfectant
1896 earliest recorded use in experiments on water supplies
1897 used in England to sterilize water mains following typhoid
outbreak
1902 first continuous use in water supplies in Belgium
1909 liquid chlorine (compressed gas) became commercially
available
Subsequent rapid spread in use of chlorine throughout the world
WWI: Chlorine gas used as chemical warfare ag
Chlorination and Typhoid fever
Chlorination
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Hypochlorite may either be added directly (i.e., in the form of
bleach) or created within water by bubbling chlorine gas through
the water
Chlorine gas - preferred for medium to large disinfection
systems
Sodium Hypochlorite (liquid) - typically used for small
disinfection systems and large swimming pools
Calcium Hypochlorite (powder, tablet) - typically used for private
swimming pools
For water purification, do not use scented bleach
Bromine sometimes used as a less-smelly alternative
Hypochlorite is less effective in the presence of significant
organic compounds
Chlorination
n
n
“What is known as modern chemical warfare began during
World War I. The first chemical agent to be used was large
amounts of chlorine gas, about one hundred sixty tons, which
was released from 6,000 pressurized cylinders into the wind by
the Germans against the Allies. The chlorine floated in a huge
clouds toward the Allies until it reached the Allied lines causing
men to die from the effects of the chlorine gas. Because of the
large amounts of gas released the chlorine caused large
amounts of yellowish fluid to form in the lungs of its victim, also
causing eye, nose, and throat burning before causing death by
choking.”
http://www.geocities.com/CapeCanaveral/Lab/4239/chemweapo
ns/history.html
Iodine
Iodophores
Alcohols
n
n
Isopropanol & ethanol
Advantages
n
n
Disadvantages
n
n
n
n
kill vegetative bacteria on clean surfaces in 30
seconds
inactive against spores, fungi
Inflammable
Need to be at correct % with water (65-80%)
Practical uses
n
n
n
Skin antisepsis before venepuncture
Hand rubs
Disinfection of e.g. trolley tops
Alcohols
u
u
u
u
u
Kill bacteria, fungi, but not endospores or naked
viruses.
Act by denaturing proteins and disrupting cell
membranes.
Evaporate, leaving no residue.
Used to mechanically wipe microbes off skin before
injections or blood drawing.
Not good for open wounds, because cause proteins
to coagulate.
u
u
Ethanol: Drinking alcohol. Optimum concentration is 70%
Isopropanol: Rubbing alcohol. Better disinfectant than
ethanol. Also cheaper and less volatile.
Alcohols
n
n
n
n
n
n
n
Aqueous ethanol (60-95%) and isopropanol are used
as disinfectants
Effectively kill bacteria and fungi but not endospores
nor nonenveloped viruses
Fast acting, no residue (evaporate away), no staining
But not very penetrating and no residual activity
(once gone gone)
Exert their action by denaturing proteins and
dissolving lipids
In tinctures, they enhance the effectiveness of other
antimicrobial chemicals
Flammable; also may damage rubber, plastic, etc.
Tinctures
A tincture is a nonvolatile substance
(medicine) presented as an alcohol solution,
e.g., (for fun with numerous [sic])…
Tincture
Ø “Formulae: Fresh juice of
Organic Habanero peppers,
New Mexico Jalapeno, African
Bird peppers and Hatch Chili
peppers.
Ø Dosage: Five to thirty drops,
three times daily. CAUTION ~
EXTREMELY HOT!!
Ø Therapeutic Action: Cayenne
is the greatest herbal aid to
circulation and should be used
on a regular basis. The extract
is very concentrated and gets
into the bloodstream quickly and
makes it a perfect first aid
remedy for heart attacks, stroke,
fainting, shock, dizziness,
hemorrhage, internal and
external bleeding. Use a few
drops to 10 droppers full. It has
saved many lives.
Tincture II
Tincture II
n
n
n
“Formulae: Fresh Garlic Juice, Goldenseal root, Usnea lichen, Myrrh
gum, Pine resin, Echinacea root juice, Tea Tree oil, Kelp, Black Walnut
inner hulls, Oak galls and Cayenne pepper in 80% grain alcohol.
Dosage: Generally for external use but can be used in the oral
cavity. Soak a cotton swab in the tincture and scrub into the infected
area, let air dry. It has a burning sensation. If the wound is tender, just
flush it with multiple droppers full of the tincture but no need to scrub it
in.
Therapeutic Action: There has never been an infected occur when
this formula has been used. It's excellent for treating any cut or wound
and it is anti-bacterial, anti-viral and anti-fungal. The tree resins in this
formula leave an invisible protective, anti-bacterial coating over the
wound. This formula was use on a man in England who had the top of
his knee torn off in an automobile accident. In 24 hours it literally
glued his knee back together. A nurse from Ireland on the scene said
in all the years in the hospital, she had never seen such a severe
wound close right up and heal, and with no infections.”
Heavy Metals
n
n
n
n
Ag, Cu, Hg, Ni, Zn, Ag(NO3)2, CuSO4, ZnCl2,
HgCl2
These metals (and metal ions) react with
sulfhydral (–SH) groups of proteins, denaturing
proteins
Silver nitrate is used to treat Ophthalmia
neonatorum in newborns as caused by
Neisseria gonorrhoeae
Oligodynamic action: the ability of very small
amounts of heavy metals (especially silver and
copper) to exert antimicrobial activity
Heavy Metals
Include copper, selenium, mercury, silver, and zinc.
u Oligodynamic action: Very tiny amounts are effective.
A. Silver:
u 1% silver nitrate used to protect infants against
gonorrheal eye infections until recently.
B. Mercury
u Organic mercury compounds like merthiolate and
mercurochrome are used to disinfect skin wounds.
C. Copper
u Copper sulfate is used to kill algae in pools and fish
tanks.
u
Heavy Metals
D. Selenium (硒)
u Kills fungi and their spores. Used for fungal
infections.
u Also used in dandruff (去頭皮屑) shampoos.
E. Zinc
u Zinc chloride is used in mouthwashes.
u Zinc oxide is used as antifungal agent in
paints.
Alkylating agents
n
n
Glutaraldehyde and Formaldehyde
Advantages
n
n
Disdvantages
n
n
n
n
n
Good activity against spores, virues, fungi
Glutaraldehyde only moderately active against TB
Need long exposure time for full effect (3 hours)
freshness & pH critical
TOXIC!
Practical uses
n
n
n
Disinfection of endoscopes
Blood spills
Fumigation
Aldehydes
Include some of the most effective antimicrobials.
u Inactivate proteins by forming covalent crosslinks
with several functional groups.
A. Formaldehyde gas:
u Excellent disinfectant.
u Commonly used as formalin, a 37% aqueous
solution.
u Formalin was used extensively to preserve biological
specimens and inactivate viruses and bacteria in
vaccines.
u Irritates mucous membranes, strong odor.
u Also used in mortuaries for embalming.
u
Aldehydes
B. Glutaraldehyde:
u Less irritating and more effective than formaldehyde.
u One of the few chemical disinfectants that is a
sterilizing agent.
u A 2% solution of glutaraldehyde (Cidex) is:
u
u
u
u
Bactericidal, tuberculocidal, and viricidal in 10 minutes.
Sporicidal in 3 to 10 hours.
Commonly used to disinfect hospital instruments.
Also used in mortuaries for embalming.
Glutaraldehyde
Glutaraldehyde is capable of effectiving
sterilization—at room temperature,
even against endospores,
and even in the presence of organics,
but achieving sterilization requries many
hours of exposure… and it is nasty stuff to
work with!
Gaseous Chemosterilizers
n
n
n
n
n
Propylene oxide (C3H6O)
Chlorine gas (Cl2)
Chlorine dioxide (ClO2)
Ozone (O3)
Ethylene oxide (C2H4O)…
Gaseous Chemosterilizers
n
n
n
n
n
n
to sterilize heat- or moisture-sensitive items
for items damaged by heat or moisture
is not corrosive, not damaging to delicate
instruments, microscopes, disposable plastic
instruments and materials
permeates porous materials
dissipates rapidly from material
but is costly, toxic, carcinogenic, explosive,
and relatively lengthy process
Gaseous Sterilizers
Chemicals that sterilize in a chamber similar to an
autoclave.
u Denature proteins, by replacing functional groups
with alkyl groups.
A. Ethylene Oxide:
u Kills all microbes and endospores, but requires
exposure of 4 to 18 hours.
u Toxic and explosive in pure form.
u Highly penetrating.
u Most hospitals have ethylene oxide chambers to
sterilize mattresses and large equipment.
u
Ethylene oxide
n
n
n
n
Highly toxic flammable gas, kills spores!
Used for bulky items such as heart lung
machines
Can be used on glutaraldehyde-labile
endoscopes
Use limited by safety issues
Oxidizing Agents
n
n
n
n
n
n
HOOH, hydrogen peroxide, is most common
HOOH is not a terribly effective disinfectant or
anticeptic
This is because bacteria and body tissues contain
enzymes (catalase) that inactivate hydrogen peroxide
However, the oxygen released upon inactivation can
help oxygenate deep wounds and thus kill strictanaerobe contaminants, e.g., Clostridium tetani
Ozone and peracetic acid are also oxidizing
antimicrobial agents
They exert their effect by oxidizing cell
macromolecules (e.g., proteins, DNA, etc.)
Peroxygens (Oxidizing Agents)
Oxidize cellular components of treated microbes.
u Disrupt membranes and proteins.
A. Ozone:
u Used along with chlorine to disinfect water.
u Helps neutralize unpleasant tastes and odors.
u More effective killing agent than chlorine, but less
stable and more expensive.
u Highly reactive form of oxygen.
u Made by exposing oxygen to electricity or UV light.
u
Peroxygens (Oxidizing Agents)
B. Hydrogen Peroxide:
u Used as an antiseptic.
u Not good for open wounds because quickly broken
down by catalase present in human cells.
u Effective in disinfection of inanimate objects.
u Sporicidal at higher temperatures.
u Used by food industry and to disinfect contact lenses.
C. Benzoyl Peroxide:
u Used in acne medications.
Peroxygens (Oxidizing Agents)
D. Peracetic Acid:
u One of the most effective liquid sporicides
available.
u Sterilant :
u
u
u
Kills bacteria and fungi in less than 5 minutes.
Kills endospores and viruses within 30 minutes.
Used widely in disinfection of food and
medical instruments because it does not leave
toxic residues.
Efficiency of Different
Chemical Antimicrobial Agents
Chemical Antimicrobials
* Type of Disinfectant: H = High level; I = Intermediate level; L = Low level
The Problem of CJD and
TSEs
n
n
n
Creutzfeld-Jakob syndrome and other transmissible
spongiform encephalopathies caused by highly
resistant proteinaceous particles, prions
can survive 3 years of environmental exposure and
are unusually resistant to conventional
decontamination methods
Iatrogenic CJD documented in three circumstances
n
n
n
use of contaminated medical equipment (2 cases)
use of extracted pituitary hormones (> 130 cases)
implantation of contaminated grafts from humans (cornea, 3
cases; dura mater, > 110 cases)
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