sterilization and chemotherapy 王淑鶯微生物免疫學所國立成功大學醫學院分機 :...

Sterilization and ChemotherapySterilization and Chemotherapy

王淑鶯王淑鶯微生物免疫學所微生物免疫學所國立成功大學醫學院國立成功大學醫學院

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Email: [email protected]: [email protected]

Definition of Sterilization and DisinfectionDefinition of Sterilization and Disinfection

Physical and Chemical Methods of Antimicrobial ControlPhysical and Chemical Methods of Antimicrobial Control

Antibiotics and Mechanisms of Antimicrobial ActionAntibiotics and Mechanisms of Antimicrobial Action

References: References:

Chapters 8 & 20 in Medical Microbiology Chapters 8 & 20 in Medical Microbiology

(Murray, P. R. et al; 6(Murray, P. R. et al; 6thth edition) edition)

OutlineOutline

Early civilizations practiced salting, smoking, pickling, Early civilizations practiced salting, smoking, pickling, drying, and exposure of food and clothing to sunlight to drying, and exposure of food and clothing to sunlight to control microbial growth.control microbial growth.Use of spices in cooking was to mask taste of spoiled Use of spices in cooking was to mask taste of spoiled food. Some spices prevented spoilage.food. Some spices prevented spoilage. In mid 1800s Semmelweiss and Lister helped developed In mid 1800s Semmelweiss and Lister helped developed asepticaseptic techniquestechniques to prevent contamination of surgical to prevent contamination of surgical wounds. Before then:wounds. Before then:• Nosocomial infections caused death in 10% of Nosocomial infections caused death in 10% of

surgeries.surgeries.• Up to 25% mothers delivering in hospitals died due to Up to 25% mothers delivering in hospitals died due to

infection infection

Antimicrobial DefinitionsAntimicrobial Definitions

SterilizationSterilization– To completely remove all kinds of microbes (bacteria, To completely remove all kinds of microbes (bacteria,

mycobacteria, viruses, & fungi) by physical or chemical mycobacteria, viruses, & fungi) by physical or chemical methodsmethods

– Effective to kill “bacterium spores”Effective to kill “bacterium spores”– Sterilant: material or method used to remove or kill all Sterilant: material or method used to remove or kill all

microbesmicrobes

Antimicrobial DefinitionsAntimicrobial Definitions

DisinfectionDisinfection– To To reducereduce the number of pathogenic microorganisms to the point the number of pathogenic microorganisms to the point

where they no longer cause diseaseswhere they no longer cause diseases– Usually involves the removal of Usually involves the removal of vegetativevegetative or or non-endosporenon-endospore

formingforming pathogens pathogens– May use physical or chemical methodsMay use physical or chemical methods

Disinfectant: An agent applied to inanimate objects.Disinfectant: An agent applied to inanimate objects.

Antiseptic: A substance applied to living tissue.Antiseptic: A substance applied to living tissue.

Degerming: Removal of most microbes in a limited area. Degerming: Removal of most microbes in a limited area. Example: Alcohol swab on skin.Example: Alcohol swab on skin.

Sanitization: Use of chemical agent on food-handling Sanitization: Use of chemical agent on food-handling equipment to meet public health standards and minimize equipment to meet public health standards and minimize chances of disease transmission. e.g.: Hot soap & waterchances of disease transmission. e.g.: Hot soap & water

Antimicrobial DefinitionsAntimicrobial DefinitionsBacteriostaticBacteriostatic– prevents growth of bacteriaprevents growth of bacteria

GermicideGermicide– An agent that kills certain microorganisms.An agent that kills certain microorganisms.

Bactericide: An agent that kills bacteria. Most do Bactericide: An agent that kills bacteria. Most do not kill endospores.not kill endospores.

Viricide: An agent that inactivates viruses.Viricide: An agent that inactivates viruses.

Fungicide: An agent that kills fungi.Fungicide: An agent that kills fungi.

Sporicide: An agent that kills bacterial endospores of Sporicide: An agent that kills bacterial endospores of fungal spores.fungal spores.

Method of ControlMethod of Control

physical or chemical?physical or chemical?– physical control includes heat, irradiation, filtration physical control includes heat, irradiation, filtration

and mechanical removaland mechanical removal– chemical control involves the use of antimicrobial chemical control involves the use of antimicrobial

chemicalschemicals– depends on the situationdepends on the situation– degree of control requireddegree of control required

air filtersantimicrobial chemicals

Factors influence the effectiveness Factors influence the effectiveness of antimicrobial treatmentof antimicrobial treatment

Number of MicrobesNumber of Microbes: The more microbes present, the more time it : The more microbes present, the more time it takes to eliminate population.takes to eliminate population.

Type of MicrobesType of Microbes: Endospores are very difficult to destroy. : Endospores are very difficult to destroy. Vegetative pathogens vary widely in susceptibility to different Vegetative pathogens vary widely in susceptibility to different methods of microbial control.methods of microbial control.

Environmental influences:Environmental influences: Presence of organic material (blood, Presence of organic material (blood, feces, saliva, pH etc.) tends to inhibit antimicrobials.feces, saliva, pH etc.) tends to inhibit antimicrobials.

Time of Exposure:Time of Exposure: Chemical antimicrobials and radiation Chemical antimicrobials and radiation treatments are more effective at longer times. In heat treatments, treatments are more effective at longer times. In heat treatments, longer exposure compensates for lower temperatures.longer exposure compensates for lower temperatures.

Rate of Microbial DeathRate of Microbial Death

When bacterial populations are heated or treated When bacterial populations are heated or treated antimicrobial chemicals, they usually die at a constant antimicrobial chemicals, they usually die at a constant rate.rate.

Physical Methods of Microbial ControlPhysical Methods of Microbial Control

heatheat

filtrationfiltration

radiationradiation


HeatHeat– Kills microorganisms by denaturing their enzymes and other Kills microorganisms by denaturing their enzymes and other

proteins. Heat resistance varies widely among microbes.proteins. Heat resistance varies widely among microbes.– fast, reliable, inexpensivefast, reliable, inexpensive– does not introduce potential toxic substancesdoes not introduce potential toxic substances

types of heat control includetypes of heat control include– moist heatmoist heat– pasteurizationpasteurization– dry heatdry heat


Moist Heat: Moist Heat: Kills microorganisms byKills microorganisms by coagulating coagulating their proteins. their proteins.

Boiling:Boiling: Heat to 100 Heat to 100ooC or more at sea level. Kills C or more at sea level. Kills vegetative forms of bacterial pathogens. Most pathogens vegetative forms of bacterial pathogens. Most pathogens can be killed within 10 minutes or less. Endospores and can be killed within 10 minutes or less. Endospores and some viruses are not destroyed this quickly. some viruses are not destroyed this quickly.

In general, moist heat is much more effective than In general, moist heat is much more effective than dry heat.dry heat.


Moist Heat (Continued): Moist Heat (Continued):

Reliable sterilization with moist heat requires Reliable sterilization with moist heat requires temperatures above that of boiling water.temperatures above that of boiling water.

Autoclave:Autoclave: Chamber which is filled with hot steam under Chamber which is filled with hot steam under pressure. Preferred method of sterilization, unless material pressure. Preferred method of sterilization, unless material is damaged by heat, moisture, or high pressure.is damaged by heat, moisture, or high pressure.

Temperature of steam reaches Temperature of steam reaches 121121ooC C at twice at twice atmospheric pressure.atmospheric pressure.

All organisms and endospores are killed within 15 All organisms and endospores are killed within 15 minutes.minutes.

Autoclave: Closed Chamber with High Autoclave: Closed Chamber with High Temperature and PressureTemperature and Pressure


Moist Heat (Continued): Moist Heat (Continued): Pasteurization:Pasteurization: Developed by Louis Pasteur to prevent Developed by Louis Pasteur to prevent

the spoilage of beverages. Used to reduce microbes the spoilage of beverages. Used to reduce microbes responsible for spoilage of beer, milk, wine, juices, etc.responsible for spoilage of beer, milk, wine, juices, etc.

Classic Method of PasteurizationClassic Method of Pasteurization: Milk was : Milk was exposed to 65exposed to 65ooC for 30 minutes.C for 30 minutes.

High Temperature Short Time Pasteurization High Temperature Short Time Pasteurization (HTST):(HTST): Used today. Milk is exposed to 72 Used today. Milk is exposed to 72ooC for 15 C for 15 seconds.seconds.


Dry Heat:Dry Heat: Direct Flaming:Direct Flaming: Used to sterilize inoculating loops and Used to sterilize inoculating loops and

needles. Heat metal until it has a red glow.needles. Heat metal until it has a red glow. IncinerationIncineration: Effective way to sterilize disposable items : Effective way to sterilize disposable items

(paper cups, dressings) and biological waste.(paper cups, dressings) and biological waste. Hot Air Sterilization:Hot Air Sterilization: Place objects in an oven. Require Place objects in an oven. Require

2 hours at 1702 hours at 170ooC for sterilization. Dry heat is transfers C for sterilization. Dry heat is transfers heat less effectively to a cool body, than moist heat.heat less effectively to a cool body, than moist heat.


Filtration: Filtration: Removal of microbes by passage of a liquid or Removal of microbes by passage of a liquid or gas through a screen like material with small pores. gas through a screen like material with small pores. Used to sterilize heat sensitive materials like vaccines, Used to sterilize heat sensitive materials like vaccines, enzymes, antibiotics, and some culture media.enzymes, antibiotics, and some culture media.

Membrane FiltersMembrane Filters: Uniform pore size. Used in industry and : Uniform pore size. Used in industry and research. Different sizes:research. Different sizes:

0.22 and 0.45um Pores0.22 and 0.45um Pores: Used to filter most bacteria. Don’t : Used to filter most bacteria. Don’t retain spirochetes, mycoplasmas and viruses.retain spirochetes, mycoplasmas and viruses.

0.01 um Pores0.01 um Pores: Retain all viruses and some large proteins.: Retain all viruses and some large proteins. High Efficiency Particulate Air Filters (HEPA):High Efficiency Particulate Air Filters (HEPA): Used in operating Used in operating

rooms to remove bacteria from air.rooms to remove bacteria from air.


FiltrationFiltrationused for heat sensitive used for heat sensitive fluidsfluids

airair


Low Temperature: Low Temperature: Effect depends on microbe and Effect depends on microbe and treatment applied.treatment applied.

Refrigeration:Refrigeration: Temperatures from 0 to 7 Temperatures from 0 to 7ooC. C. BacteriostaticBacteriostatic effecteffect. .

Reduces metabolic rate of most microbes so they cannot Reduces metabolic rate of most microbes so they cannot reproduce or produce toxins.reproduce or produce toxins.

FreezingFreezing: Temperatures below 0: Temperatures below 0ooC. C.


Desiccation: Desiccation: In the absence of water, microbes cannot In the absence of water, microbes cannot grow or reproduce, but some may remain viable for grow or reproduce, but some may remain viable for years. After water becomes available, they start growing years. After water becomes available, they start growing again.again.

Susceptibility to desiccation varies widely:Susceptibility to desiccation varies widely: Neisseria gonnorrheaNeisseria gonnorrhea: Only survives about one hour.: Only survives about one hour. Mycobacterium tuberculosisMycobacterium tuberculosis: May survive several months.: May survive several months. Viruses are fairly resistant to desiccation.Viruses are fairly resistant to desiccation. Clostridium sppClostridium spp. and . and Bacillus sppBacillus spp.: May survive decades..: May survive decades.


Osmotic Pressure: Osmotic Pressure: The use of high concentrations of salts The use of high concentrations of salts and sugars in foods is used to increase the osmotic and sugars in foods is used to increase the osmotic pressure and create a pressure and create a hypertonichypertonic environment. environment.

PlasmolysisPlasmolysis: As water leaves the cell, plasma membrane : As water leaves the cell, plasma membrane shrinks away from cell wall. shrinks away from cell wall.

Yeasts and molds:Yeasts and molds: More resistant to high osmotic pressures. More resistant to high osmotic pressures. Staphylococci spp.Staphylococci spp. that live on skin are fairly resistant to high osmotic that live on skin are fairly resistant to high osmotic

pressure.pressure.


Radiation: Radiation: Three types of radiation kill microbes:Three types of radiation kill microbes:

1. Ionizing Radiation: 1. Ionizing Radiation: Gamma rays, X rays, electron Gamma rays, X rays, electron beams, or higher energy rays. Have short wavelengths beams, or higher energy rays. Have short wavelengths (less than 1 nanometer). (less than 1 nanometer).

Used to sterilize pharmaceuticals, disposable medical Used to sterilize pharmaceuticals, disposable medical supplies and food.supplies and food.

DisadvantagesDisadvantages: Penetrates human tissues. May cause : Penetrates human tissues. May cause genetic mutations in humans.genetic mutations in humans.

Forms of RadiationForms of Radiation



2. Ultraviolet light (Nonionizing Radiation):2. Ultraviolet light (Nonionizing Radiation): Wavelength is longer than 1 nanometer. Damages DNA Wavelength is longer than 1 nanometer. Damages DNA by producing thymine dimers, which cause mutations.by producing thymine dimers, which cause mutations.

Used to disinfect operating rooms, nurseries, cafeterias. Used to disinfect operating rooms, nurseries, cafeterias.

DisadvantagesDisadvantages: Damages skin, eyes. Doesn’t : Damages skin, eyes. Doesn’t penetrate paper, glass, and cloth.penetrate paper, glass, and cloth.



3.3. Microwave Radiation:Microwave Radiation: Wavelength ranges from 1 Wavelength ranges from 1 millimeter to 1 meter. millimeter to 1 meter.

Heat is absorbed by water molecules. Heat is absorbed by water molecules.

May kill vegetative cells in moist foods. May kill vegetative cells in moist foods.

Bacterial endospores, which do not contain water, are Bacterial endospores, which do not contain water, are not damaged by microwave radiation. not damaged by microwave radiation.

Solid foods are unevenly penetrated by microwaves.Solid foods are unevenly penetrated by microwaves.

Chemical Methods of Microbial ControlChemical Methods of Microbial ControlTypes of DisinfectantsTypes of Disinfectants

1. Phenols and Phenolics:1. Phenols and Phenolics: PhenolPhenol (carbolic acid) was first used by Lister as a (carbolic acid) was first used by Lister as a

disinfectant.disinfectant. Rarely used today because it is a skin irritant and has Rarely used today because it is a skin irritant and has

strong odor.strong odor. PhenolicsPhenolics are chemical derivatives of phenol are chemical derivatives of phenol

Cresols (Lysol)Cresols (Lysol): Derived from coal tar.: Derived from coal tar. BiphenolsBiphenols: Effective against gram-positive staphylococci : Effective against gram-positive staphylococci

and streptococci. Excessive use in infants may cause and streptococci. Excessive use in infants may cause neurological damage.neurological damage.

Destroy plasma membranes and denature proteins.Destroy plasma membranes and denature proteins. AdvantagesAdvantages: Stable, persist for long times after applied, : Stable, persist for long times after applied,

and remain active in the presence of organic compounds.and remain active in the presence of organic compounds.


2. Halogens: 2. Halogens: Effective alone or in compounds.Effective alone or in compounds.A.A. Iodine:Iodine: Iodine tincture (alcohol solution) was one of first Iodine tincture (alcohol solution) was one of first

antiseptics used.antiseptics used.

B. Chlorine:B. Chlorine: When mixed in water forms When mixed in water forms hypochloroushypochlorous acidacid::

ClCl22 + H + H22O ------>O ------> H+ + Cl-H+ + Cl- + HOCl+ HOCl

HypochlorousHypochlorous acidacid

Used to disinfect drinking water, pools, and sewage.Used to disinfect drinking water, pools, and sewage.


3. Alcohols: 3. Alcohols: Kill bacteria, fungi, but not endospores or naked viruses.Kill bacteria, fungi, but not endospores or naked viruses. Act by denaturing proteins and disrupting cell membranes.Act by denaturing proteins and disrupting cell membranes. Used to mechanically wipe microbes off skin before Used to mechanically wipe microbes off skin before

injections or blood drawing.injections or blood drawing. Not good for open wounds, because cause proteins to Not good for open wounds, because cause proteins to

coagulate.coagulate. EthanolEthanol: Drinking alcohol. Optimum concentration is : Drinking alcohol. Optimum concentration is

70%.70%. IsopropanolIsopropanol: Rubbing alcohol. Better disinfectant than : Rubbing alcohol. Better disinfectant than

ethanol. Also cheaper and less volatile.ethanol. Also cheaper and less volatile.


4. Heavy Metals: 4. Heavy Metals: Include copper, selenium, mercury, silver, and zinc.Include copper, selenium, mercury, silver, and zinc. Very tiny amounts are effective.Very tiny amounts are effective.

A. Silver:A. Silver: 1% silver nitrate used to protect infants against gonorrheal 1% silver nitrate used to protect infants against gonorrheal

eye infections, now has been replaced by erythromycin.eye infections, now has been replaced by erythromycin.

B. MercuryB. Mercury Organic mercury compounds like merthiolate and Organic mercury compounds like merthiolate and

mercurochrome are used to disinfect skin wounds.mercurochrome are used to disinfect skin wounds.

C. CopperC. Copper Copper sulfate is used to kill algae in pools and fish tanks.Copper sulfate is used to kill algae in pools and fish tanks.


5. Quaternary Ammonium Compounds (Quats): 5. Quaternary Ammonium Compounds (Quats): Cationic (positively charge) detergents.Cationic (positively charge) detergents. Effective against gram positive bacteria, less effective Effective against gram positive bacteria, less effective

against gram-negative bacteria.against gram-negative bacteria.


6. Aldehydes: 6. Aldehydes: Include some of the most effective antimicrobials.Include some of the most effective antimicrobials. Inactivate proteins by forming covalent crosslinks with Inactivate proteins by forming covalent crosslinks with

several functional groups.several functional groups.A. Formaldehyde:A. Formaldehyde: Excellent disinfectant, 2% aqueous solution.Excellent disinfectant, 2% aqueous solution. Commonly used as Commonly used as formalinformalin, a 37% aqueous solution., a 37% aqueous solution. Formalin was used extensively to preserve biological Formalin was used extensively to preserve biological

specimens and inactivate viruses and bacteria in specimens and inactivate viruses and bacteria in vaccines.vaccines.

Irritates mucous membranes, strong odor.Irritates mucous membranes, strong odor.


6. Aldehydes: 6. Aldehydes: B. Glutaraldehyde:B. Glutaraldehyde: Less irritating and more effective than formaldehyde.Less irritating and more effective than formaldehyde. Commonly used to disinfect hospital instruments.Commonly used to disinfect hospital instruments.

7. Gaseous Sterilizers: 7. Gaseous Sterilizers: Chemicals that sterilize in a chamber similar to an Chemicals that sterilize in a chamber similar to an

autoclave.autoclave. Denature proteins, by replacing functional groups with alkyl Denature proteins, by replacing functional groups with alkyl

groups.groups.

Ethylene Oxide:Ethylene Oxide: Kills all microbes and endospores, but requires exposure of Kills all microbes and endospores, but requires exposure of

4 to 18 hours.4 to 18 hours.

Chemical Methods of Microbial ControlChemical Methods of Microbial ControlTypes of DisinfectantsTypes of Disinfectants8. Oxidizing Agents: 8. Oxidizing Agents: Oxidize cellular components of treated microbes.Oxidize cellular components of treated microbes. Disrupt membranes and proteins.Disrupt membranes and proteins.

A. Ozone:A. Ozone: Used along with chlorine to disinfect water.Used along with chlorine to disinfect water. Helps neutralize unpleasant tastes and odors.Helps neutralize unpleasant tastes and odors. More effective killing agent than chlorine, but less stable and more More effective killing agent than chlorine, but less stable and more

expensive.expensive. Highly reactive form of oxygen.Highly reactive form of oxygen. Made by exposing oxygen to electricity or UV lightMade by exposing oxygen to electricity or UV light

B. Hydrogen Peroxide:B. Hydrogen Peroxide: Not good for open wounds because quickly broken down by catalase Not good for open wounds because quickly broken down by catalase

present in human cells.present in human cells. Effective in disinfection of inanimate objectsEffective in disinfection of inanimate objects

Definition of Sterilization and DisinfectionDefinition of Sterilization and Disinfection

Physical and Chemical Methods of antimicrobial controlPhysical and Chemical Methods of antimicrobial control

Antibiotics and Mechanisms of Antimicrobial ActionAntibiotics and Mechanisms of Antimicrobial Action

OutlineOutline

Definition of an AntibioticDefinition of an Antibiotic

Substance produced by a microorganism or a similar Substance produced by a microorganism or a similar product produced wholly (synthetic) or partially (semi-product produced wholly (synthetic) or partially (semi-synthetic) by chemical synthesis and in low synthetic) by chemical synthesis and in low concentrations inhibits the growth of or kills concentrations inhibits the growth of or kills microorganisms.microorganisms.

Microbial Microbial Sources of Sources of AntibioticsAntibiotics

Antibiotic Antibiotic Spectrum of ActivitySpectrum of Activity

No antibiotic is effective against all microbesNo antibiotic is effective against all microbes

Mechanisms of Antimicrobial ActionMechanisms of Antimicrobial Action

Bacteria have their own enzymes forBacteria have their own enzymes for– Cell wall formationCell wall formation– Protein synthesisProtein synthesis– DNA replicationDNA replication– RNA synthesisRNA synthesis– Synthesis of essential metabolitesSynthesis of essential metabolites

Modes of Antimicrobial ActionModes of Antimicrobial Action

Bacteria cell wall contains Bacteria cell wall contains peptidoglycanpeptidoglycan

Antimicrobials that interfere with the Antimicrobials that interfere with the synthesis of cell wall do not synthesis of cell wall do not interfere with eukaryotic cellinterfere with eukaryotic cell

Antimicrobials of this class includeAntimicrobials of this class include

β- lactam drugsβ- lactam drugs

Vancomycin Vancomycin

DaptomycinDaptomycin

BacitracinBacitracin

Antibacterial AntibioticsAntibacterial Antibiotics Inhibitors of Cell Wall Synthesis Inhibitors of Cell Wall Synthesis

Penicillins and Cephalosporins Penicillins and Cephalosporins – Part of group of drugs called β –Part of group of drugs called β –

lactamslactams

Have shared chemical structure Have shared chemical structure called β-lactam ringcalled β-lactam ring

– Competitively inhibits function of Competitively inhibits function of penicillin-binding proteins (involved in penicillin-binding proteins (involved in the final stages of the synthesis of the final stages of the synthesis of

peptidoglycanpeptidoglycan))Inhibits peptide bridge formation Inhibits peptide bridge formation between glycan moleculesbetween glycan molecules

This causes the cell wall to This causes the cell wall to develop weak points at the growth develop weak points at the growth sites and become fragile.sites and become fragile.


The weakness in the cell wall The weakness in the cell wall causes the cell to lyze.causes the cell to lyze.


Natural penicillinsNatural penicillins

Narrow range of actionNarrow range of action

Susceptible to Susceptible to penicillinase (penicillinase ( lactamase) lactamase)

Semisynthetic PenicillinsSemisynthetic Penicillins– Penicilinase-resistant penicillinsPenicilinase-resistant penicillins

Carbapenems: very broad spectrumCarbapenems: very broad spectrum

Monobactam: Gram negativeMonobactam: Gram negative– Extended-spectrum penicillinsExtended-spectrum penicillins


Antibacterial AntibioticsAntibacterial Antibiotics Inhibitors of Cell Wall Synthesis Inhibitors of Cell Wall SynthesisCephalosporinsCephalosporins– chemical structures make them resistant to chemical structures make them resistant to

inactivation by certain inactivation by certain ββ-lactamases-lactamases– most effective against Gram – bacteria.most effective against Gram – bacteria.– chemically modified to produce family of related chemically modified to produce family of related

compoundscompounds

22ndnd, 3, 3rdrd, and 4, and 4thth generations more effective against generations more effective against gram-negatives (4gram-negatives (4thth generation against almost generation against almost Enterobacteriaceae and Enterobacteriaceae and Pseudomonas aeruginosa) Pseudomonas aeruginosa)

Antibacterial AntibioticsAntibacterial Antibiotics Inhibitors of Cell Wall Synthesis Inhibitors of Cell Wall SynthesisBacitracinBacitracin– Interferes with transport of peptidoglycan precursors Interferes with transport of peptidoglycan precursors

across cytoplasmic membraneacross cytoplasmic membrane– Toxicity limits use to topical applicationsToxicity limits use to topical applications– Common ingredient in non-prescription first-aid Common ingredient in non-prescription first-aid

ointmentsointments


VancomycinVancomycin– Inhibits formation of glycan chainsInhibits formation of glycan chains– Important in treating infections caused by penicillin Important in treating infections caused by penicillin

resistant Gram + organismsresistant Gram + organisms– Acquired resistance most often due to alterations in side Acquired resistance most often due to alterations in side

chain of NAM moleculechain of NAM molecule

Prevents binding of vancomycin to NAM component Prevents binding of vancomycin to NAM component of glycanof glycan

– Important "last line" against antibiotic resistant Important "last line" against antibiotic resistant S. aureusS. aureus

Antibacterial AntibioticsAntibacterial Antibiotics Inhibitors of Inhibitors of Protein SynthesisProtein Synthesis

Inhibition of protein synthesisInhibition of protein synthesis– Structure of prokaryotic ribosome acts as target for Structure of prokaryotic ribosome acts as target for

many antimicrobials of this classmany antimicrobials of this class

Differences in prokaryotic and eukaryotic Differences in prokaryotic and eukaryotic ribosomes responsible for selective toxicityribosomes responsible for selective toxicity

– Drugs of this class includeDrugs of this class include

AminoglycosidesAminoglycosides

TetracyclinsTetracyclins

MacrolidsMacrolids

ChloramphenicolChloramphenicol


AminoglycosidesAminoglycosides– binds to ribosomal subunitsbinds to ribosomal subunits– Examples of aminoglycosides includeExamples of aminoglycosides include

Gentamicin, streptomycin and neomycin Gentamicin, streptomycin and neomycin – Often used in synergistic combination with Often used in synergistic combination with ββ-lactam drugs-lactam drugs

Allows aminoglycosides to enter cells that are often Allows aminoglycosides to enter cells that are often resistantresistant

– Side effectsSide effectsNephrotoxicityNephrotoxicity


TetracyclinsTetracyclins– Reversibly bind 30S ribosomal subunitReversibly bind 30S ribosomal subunit

Blocks attachment of tRNA to ribosome Blocks attachment of tRNA to ribosome – Effective against certain Gram + and Gram –Effective against certain Gram + and Gram –– Can cause discoloration of teeth if taken as young childCan cause discoloration of teeth if taken as young child


MacrolidsMacrolids– Reversibly binds to 50S ribosomeReversibly binds to 50S ribosome

Prevents continuation of protein Prevents continuation of protein synthesissynthesis

– Effective against variety of Gram + Effective against variety of Gram + organisms and those responsible for organisms and those responsible for atypical pneumoniaatypical pneumonia

– Often drug of choice for patients Often drug of choice for patients allergic to penicillinallergic to penicillin

– Macrolids includeMacrolids includeErythromycin, clarithromycin and Erythromycin, clarithromycin and azithromycinazithromycin


ChloramphenicolChloramphenicol– Binds to 50S ribosomal subunitBinds to 50S ribosomal subunit

Prevents peptide bonds from forming and blocking Prevents peptide bonds from forming and blocking proteins synthesisproteins synthesis

– Effective against a wide variety of organismsEffective against a wide variety of organisms– Generally used as drug of last resort for life-threatening Generally used as drug of last resort for life-threatening

infectionsinfections– Rare but lethal side effect is aplastic anemia (because it Rare but lethal side effect is aplastic anemia (because it

disrupts protein synthesis in human bone marrow cells)disrupts protein synthesis in human bone marrow cells)

Antibacterial AntibioticsAntibacterial Antibiotics Inhibitors of Inhibitors of Nucleic Acid SynthesisNucleic Acid SynthesisFluoroquinolonesFluoroquinolones– Inhibit action of topoisomerase DNA gyraseInhibit action of topoisomerase DNA gyrase– Examples includeExamples include

Ciprofloxacin and ofloxacinCiprofloxacin and ofloxacin– Urinary tract infections Urinary tract infections

RifamycinsRifamycins– Block prokaryotic RNA polymeraseBlock prokaryotic RNA polymerase– Primarily used to treat tuberculosis and preventing Primarily used to treat tuberculosis and preventing

meningitis after exposure to meningitis after exposure to N. meningitidisN. meningitidis

Antibacterial AntibioticsAntibacterial Antibiotics Inhibitors of Inhibitors of Metabolic PathwayMetabolic Pathway

Sulfonamides (sulfa drugs)Sulfonamides (sulfa drugs)– Inhibit folic acid synthesisInhibit folic acid synthesis– Structurally similar to para-aminobenzoic acidStructurally similar to para-aminobenzoic acid

Substrate in folic acid pathwaySubstrate in folic acid pathway

Through competitive inhibition of enzyme that aids Through competitive inhibition of enzyme that aids in production of folic acidin production of folic acid

– Inhibit growth of Gram + and Gram - organismsInhibit growth of Gram + and Gram - organisms

Antibacterial AntibioticsAntibacterial Antibiotics Disruption of Plasma Membrane Disruption of Plasma Membrane

Polymyxin BPolymyxin B– Binds membrane of Gram - cellsBinds membrane of Gram - cells

Alters permeabilityAlters permeability– Leads to leakage of cell Leads to leakage of cell

and cell deathand cell deathAlso bind eukaryotic cells but Also bind eukaryotic cells but to lesser extentto lesser extent

– Limits use to topical Limits use to topical applicationapplication

– Common ingredient in first-aid Common ingredient in first-aid skin ointmentsskin ointments

Mechanisms of Antibiotic ResistanceMechanisms of Antibiotic Resistance

Enzymatic destruction of drugEnzymatic destruction of drug– Some organisms produce Some organisms produce

enzymes that chemically enzymes that chemically modify drugmodify drug

Penicillinase breaks Penicillinase breaks ββ--lactam ring of penicillin lactam ring of penicillin antibioticsantibiotics

Alteration of drug's target siteAlteration of drug's target site– Minor structural changes in Minor structural changes in

antibiotic target can prevent antibiotic target can prevent bindingbinding

Changes in ribosomal RNA Changes in ribosomal RNA prevent macrolids from prevent macrolids from binding to ribosomal binding to ribosomal subunitssubunits

Mechanisms of Antibiotic ResistanceMechanisms of Antibiotic Resistance

Prevention of penetration of drugPrevention of penetration of drug– Alterations in porin proteins decrease Alterations in porin proteins decrease

permeability of cellspermeability of cellsPrevents certain drugs from Prevents certain drugs from enteringentering

Rapid ejection of the drugRapid ejection of the drug– Some organisms produce efflux Some organisms produce efflux

pumpspumpsIncreases overall capacity of Increases overall capacity of organism to eliminate drugorganism to eliminate drug

– Enables organism to resist Enables organism to resist higher concentrations of drughigher concentrations of drug

– Tetracycline resistanceTetracycline resistance

EFFECTS OF COMBINATIONS OF DRUGSEFFECTS OF COMBINATIONS OF DRUGS

SynergismSynergism– the chemotherapeutic effects of two drugs given the chemotherapeutic effects of two drugs given

simultaneously is simultaneously is greatergreater than the effect of either than the effect of either given alonegiven alone

– For example, penicillin and streptomycin in the For example, penicillin and streptomycin in the treatment of bacterial endocarditis. Damage to treatment of bacterial endocarditis. Damage to bacterial cell walls by penicillin makes it easier for bacterial cell walls by penicillin makes it easier for streptomycin to enterstreptomycin to enter

EFFECTS OF COMBINATIONS OF DRUGSEFFECTS OF COMBINATIONS OF DRUGS

AntagonismAntagonism– the chemotherapeutic effects of two drugs given the chemotherapeutic effects of two drugs given

simultaneouslysimultaneously reduce reduce the effect of either given alone the effect of either given alone– For example, the simultaneous use of penicillin and For example, the simultaneous use of penicillin and

tetracycline is often less effective than when wither tetracycline is often less effective than when wither drugs is used alone. By stopping the growth of the drugs is used alone. By stopping the growth of the bacteria, the bacteriostatic drug tetracycline interferes bacteria, the bacteriostatic drug tetracycline interferes with the action of penicillin, which requires bacterial with the action of penicillin, which requires bacterial growth.growth.

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sterilization and chemotherapy 王淑鶯微生物免疫學所國立成功大學醫學院分機 :...