Microbial Control

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Microbial Control
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Basic Principles of
Microbial Control
                                                         3




Basic Principles of Microbial Control

• Action of Antimicrobial Agents
  ▫ Alteration of cell walls and membranes
    Cell wall maintains integrity of cell
      Cells burst due to osmotic effects when damaged
    Cytoplasmic membrane controls passage of
     chemicals into and out of cell
      Cellular contents leak out when damaged
    Non-enveloped viruses have greater tolerance of
     harsh conditions
                                                             4




Basic Principles of Microbial Control
• Action of Antimicrobial Agents
  ▫ Damage to proteins and nucleic acids
    Protein function depends on 3-D shape
      Extreme heat or certain chemicals denature proteins
    Chemicals, radiation, and heat can alter or destroy
     nucleic acids
      Can produce fatal mutants
      Can halt protein synthesis through action on RNA
                                                       5




The Selection of Microbial Control Methods

• Ideally, agents should be
  ▫   Inexpensive
  ▫   Fast-acting
  ▫   Stable during storage
  ▫   Capable of controlling microbial growth while
      being harmless to humans, animals, and objects
                                                             6




The Selection of Microbial Control Methods

• Factors Affecting the Efficacy of
  Antimicrobial Methods
  ▫ Site to be treated
     Harsh chemicals and extreme heat cannot be used on
      humans, animals, and fragile objects
     Method of microbial control based on site of medical
      procedure
                                                                    7


Relative susceptibilities of microbes to antimicrobial agents




                                                       Figure 9.2
                                                                   8



The Selection of Microbial Control Methods

• Factors Affecting the Efficacy of
  Antimicrobial Methods
  ▫ Relative susceptibility of microorganisms
     Germicides classified as high, intermediate, or low
      effectiveness
       High-level kill all pathogens, including endospores
       Intermediate-level kill fungal spores, protozoan cysts,
        viruses, and pathogenic bacteria
       Low-level kill vegetative bacteria, fungi, protozoa, and
        some viruses
                                                           9

Effect of temperature on the efficacy of an
antimicrobial chemical




                                              Figure 9.3
                                                               10


The Selection of Microbial Control Methods

• Methods for Evaluating Disinfectants and
  Antiseptics
  ▫ Phenol coefficient
     Evaluates efficacy of disinfectants and antiseptics by
      comparing an agent’s ability to control microbes to
      phenol
     Greater than 1.0 indicates agent is more effective
      than phenol
     Has been replaced by newer methods
                                                                 11



The Selection of Microbial Control Methods

• Methods for Evaluating Disinfectants and Antiseptics
  – Use-dilution test
    • Metal cylinders dipped into broth cultures of bacteria
    • Contaminated cylinder immersed into dilution of
      disinfectant
    • Cylinders removed and placed into tube of medium to see
      how much bacteria survived
    • Most effective agents entirely prevent growth at highest
      dilution
    • Current standard test in the U.S.
    • New standard procedure being developed
                                                           12




The Selection of Microbial Control Methods

• Methods for Evaluating Disinfectants and
  Antiseptics
  ▫ Kelsey-Sykes capacity test
     Alternative assessment approved by the
      European Union
     Bacterial suspensions added to the chemical
      being tested
     Samples removed at predetermined times and
      incubated
     Lack of bacterial reproduction reveals minimum
      time required for the disinfectant to be effective
                                                          13




The Selection of Microbial Control Methods

• Methods for Evaluating Disinfectants and
  Antiseptics
  ▫ In-use test
     Swabs taken from objects before and after
      application of disinfectant or antiseptic
     Swabs inoculated into growth medium and
      incubated
     Medium monitored for growth
     Accurate determination of proper strength and
      application procedure for each specific situation
                                                               14



Physical Methods of Microbial Control

• Heat-Related Methods
  ▫ Effects of high temperatures
     Denature proteins
     Interfere with integrity of cytoplasmic membrane
      and cell wall
     Disrupt structure and function of nucleic acids
  ▫ Thermal death point
     Lowest temperature that kills all cells in broth in 10
      min
  ▫ Thermal death time
     Time to sterilize volume of liquid at set temperature
                                                                  15




Physical Methods of Microbial Control

• Heat-Related Methods
  ▫ Moist heat
     Used to disinfect (remove organisms and spores), sanitize
      (kill organisms but not necessarily their spores), and
      sterilize (kill all organisms and spores)
     Denatures proteins and destroys cytoplasmic membranes
     More effective than dry heat
     Methods of microbial control using moist heat
         Boiling
         Autoclaving
         Pasteurization
         Ultrahigh-temperature sterilization
                                                                  16




Physical Methods of Microbial Control

• Heat-Related Methods
  ▫ Moist heat
     Boiling
       Kills vegetative cells of bacteria and fungi, protozoan
        trophozoites, and most viruses
       Boiling time is critical
        ▫ Different elevations require different boiling times
       Endospores, protozoan cysts, and some viruses can
        survive boiling
                                                                17




Physical Methods of Microbial Control

• Heat-Related Methods
  ▫ Moist heat
     Autoclaving
       Pressure applied to boiling water prevents steam from
        escaping
       Boiling temperature increases as pressure increases
       Autoclave conditions – 121ºC, 15 psi, 15 min
                                                          18


The relationship between temperature and pressure




                                             Figure 9.5
                                   19


Sterility indicator




                      Figure 9.7
                                                                   20



Physical Methods of Microbial Control

 • Heat-Related Methods
   ▫ Moist heat
      Pasteurization
        Used for milk, ice cream, yogurt, and fruit juices
        Not sterilization
        ▫ Heat-tolerant microbes survive
        Pasteurization of milk
        ▫ Batch method
        ▫ Flash pasteurization (High temp, short time)
        ▫ Ultrahigh-temperature pasteurization (very short time)
                                                              21



Pasteurization of milk
 Batch method
• The batch method uses a vat pasteurizer which consists
  of a jacketed vat surrounded by either circulating water,
  steam or heating coils of water or steam.

   In the vat the milk is heated and
   held throughout the holding period
   while being agitated. The milk may
   be cooled in the vat or removed hot
   after the holding time is completed
   for every particle.
                                                                 22


Pasteurization of milk
Flash method
• High Temperature Short Time (HTST)
• Milk is heated to 72°C (161.6°F) for at least 15 seconds.
• Used for perishable beverages like fruit and vegetable
  juices, beer, and some dairy products. Compared to
  other pasteurization processes, it maintains color and
  flavor better.
• It is done prior to filling into containers in order to kill
  spoilage microorganisms, to make the products safer and
  extend their shelf life. Flash pasteurization must be used
  in conjunction with sterile fill technology.
                                                             23


Pasteurization of milk
 Ultrahigh-temperature method
• Heating for 1-2 seconds at a temperature exceeding
  135°C (275°F), which is the temperature required to kill
  spores in milk.
• The most common UHT product is milk, but the process
  is also used for fruit juices, cream, soy milk, yogurt,
  wine, soups, and stews.
• Can cause browning and change the taste and smell of
  dairy products.
• UHT canned milk has a typical shelf life of six to nine
  months, until opened.
                                                            24



Physical Methods of Microbial Control

• Heat-Related Methods
  ▫ Moist heat
     Ultrahigh-temperature sterilization
       140ºC for 1 sec, then rapid cooling
       Treated liquids can be stored at room temperature
                                                          25



Physical Methods of Microbial Control


• Heat-Related Methods
  ▫ Dry heat
     Used for materials that cannot be sterilized with
      moist heat
     Denatures proteins and oxidizes metabolic and
      structural chemicals
     Requires higher temperatures for longer time than
      moist heat
     Incineration is ultimate means of sterilization
                                                            26



Physical Methods of Microbial Control

• Refrigeration and Freezing
  ▫ Decrease microbial metabolism, growth, and
    reproduction
     Chemical reactions occur slower at low temperatures
     Liquid water not available
  ▫ Psychrophilic microbes can multiply in
    refrigerated foods
  ▫ Refrigeration halts growth of most pathogens
  ▫ Slow freezing more effective than quick freezing
  ▫ Organisms vary in susceptibility to freezing
                                                           27



Physical Methods of Microbial Control

• Dessication and Lyophilization
  ▫ Drying (98% of the water is removed) inhibits
    growth due to removal of water
  ▫ Lyophilization (freeze-drying)
     Substance is rapidly frozen and sealed in a vacuum
     Substance may also be turned into a powder
  ▫ Used for long-term preservation of microbial
    cultures
     Prevents formation of damaging ice crystals
                                                               28


The use of dessication as a means of preserving
apricots




                                                  Figure 9.8
                                                               29



Filtration equipment used for microbial control




                                                  Figure 9.9
                                                                         30



The role of HEPA filters in biological safety cabinets


                                     High-Efficiency Particulate
                                     Arresting (HEPA) air filters are
                                     used in medical facilities,
                                     automobiles, aircraft, and
                                     homes. The filter must remove
                                     99.97% of all particles greater
                                     than 0.3 micrometer from the
                                     air that passes through.




                                                           Figure 9.10
                                                          31




Physical Methods of Microbial Control

• Osmotic Pressure
  ▫ High concentrations of salt or sugar in foods to
    inhibit growth
  ▫ Cells in hypertonic solution of salt or sugar lose
    water
  ▫ Fungi have greater ability than bacteria to survive
    hypertonic environments
                                                              32



Physical Methods of Microbial Control

• Radiation
  ▫ Ionizing radiation
     Wavelengths shorter than 1 nm
        Electron beams, gamma rays
     Ejects electrons from atoms to create ions
     Ions disrupt hydrogen bonding, cause oxidation, and
      create hydroxide ions
        Hydroxide ions denature other molecules (DNA)
     Electron beams – effective at killing but do not
      penetrate well
     Gamma rays – penetrate well but require hours to kill
      microbes
                                                                  33

Increased shelf life of food achieved by ionizing
radiation




                                                    Figure 9.11
34
                                                               35




Physical Methods of Microbial Control

• Radiation
  ▫ Nonionizing radiation
     Wavelengths greater than 1 nm
     Excites electrons, causing them to make new covalent
      bonds
       Affects 3-D structure of proteins and nucleic acids
     UV light causes pyrimidine dimers in DNA
     UV light does not penetrate well
     Suitable for disinfecting air, transparent fluids, and
      surfaces of objects
                                                                  36



Physical Methods of Microbial Control

• Biosafety Levels
  ▫ Four levels of safety in labs dealing with
    pathogens
     Biosafety Level 1 (BSL-1)
       Handling pathogens that do not cause disease in
        healthy humans
     Biosafety Level 2 (BSL-2)
       Handling of moderately hazardous agents
     Biosafety Level 3 (BSL-3)
       Handling of microbes in safety cabinets
     Biosafety Level 4 (BSL-4)
       Handling of microbes that cause severe or fatal disease
                                  37




A BSL-4 worker carries
Ebola virus cultures




                    Figure 9.12
                                                   38




Chemical Methods of Microbial Control

• Affect microbes’ cell walls, cytoplasmic
  membranes, proteins, or DNA
• Effect varies with differing environmental
  conditions
• Often more effective against enveloped viruses
  and vegetative cells of bacteria, fungi, and
  protozoa
                                                       39



Chemical Methods of Microbial Control

• Phenol and Phenolics
  ▫ Intermediate- to low-level disinfectants
  ▫ Denature proteins and disrupt cell membranes
  ▫ Effective in presence of organic matter
  ▫ Remain active for prolonged time
  ▫ Commonly used in health care settings, labs, and
    homes
  ▫ Have disagreeable odor and possible side effects
                                                    40




Chemical Methods of Microbial Control

• Alcohols
  ▫ Intermediate-level disinfectants
  ▫ Denature proteins and disrupt cytoplasmic
    membranes
  ▫ More effective than soap in removing bacteria
    from hands
  ▫ Swabbing of skin with 70% ethanol prior to
    injection
                                                        41




Chemical Methods of Microbial Control


• Halogens
  ▫ Intermediate-level antimicrobial chemicals
  ▫ Believed to damage enzymes via oxidation or by
    denaturation
  ▫ Widely used in numerous applications
     Iodine tablets, iodophores, chlorine treatment,
      bleach, chloramines, and bromine disinfection
                                                    42



Pre-op preparation for hand surgery




                                      Figure 9.14
43
                                                               44




Chemical Methods of Microbial Control

 • Oxidizing Agents
   ▫   Peroxides, ozone, and peracetic acid
   ▫   Kill by oxidation of microbial enzymes
   ▫   High-level disinfectants and antiseptics
   ▫   Hydrogen peroxide (H2O2) can disinfect and
       sterilize surfaces
        Not useful for treating open wounds due to catalase
         activity: the tissues convert it into H20 and 0ygen
         bubbles.
   ▫ Ozone treatment of drinking water
   ▫ Peracetic acid is an effective sporocide used to
     sterilize equipment
                                                              45



Chemical Methods of Microbial Control

• Surfactants
  ▫ “Surface active” chemicals
     Reduce surface tension of solvents
  ▫ Soaps and detergents
     Soaps have hydrophilic and hydrophobic ends
       Good degerming agents but not antimicrobial
     Detergents are positively charged organic surfactants
  ▫ Quats (Quaternary ammonium cations)
     Low-level disinfectants; disrupts cell membranes
     Ideal for many medical and industrial application
     Good against fungi, amoeba, and enveloped viruses,
      but not endospores, Mycobacterium tuberculosis and
      non-enveloped viruses.
                                                           46



Chemical Methods of Microbial Control

 • Heavy Metals
   ▫ Heavy-metal ions denature proteins
   ▫ Low-level bacteriostatic and fungistatic agents
   ▫ 1% silver nitrate to prevent blindness caused by N.
     gonorrhoeae
   ▫ Thimerosal used to preserve vaccines
   ▫ Copper inhibits algal growth
                                                        47



Chemical Methods of Microbial Control


• Aldehydes
  ▫ Compounds containing terminal –CHO groups
  ▫ Cross-link functional groups to denature proteins
    and inactivate nucleic acids
  ▫ Glutaraldehyde disinfects and sterilizes
  ▫ Formalin used in embalming and disinfection of
    rooms and instruments
                                                       48




Chemical Methods of Microbial Control

• Gaseous Agents
  ▫ Microbicidal and sporicidal gases used in closed
    chambers to sterilize items
  ▫ Denature proteins and DNA by cross-linking
    functional groups
  ▫ Used in hospitals and dental offices
  ▫ Disadvantages
       Can be hazardous to people
       Often highly explosive
       Extremely poisonous
       Potentially carcinogenic
                                                           49




Chemical Methods of Microbial Control

 • Enzymes
   ▫ Antimicrobial enzymes act against microorganisms
   ▫ Human tears contain lysozyme
      Digests peptidoglycan cell wall of bacteria
   ▫ Enzymes to control microbes in the environment
      Lysozyme used to reduce the number of bacteria in
       cheese
      Prionzyme can remove prions on medical
       instruments
                                                      50




Chemical Methods of Microbial Control


• Antimicrobials
  ▫ Antibiotics, semi-synthetic, and synthetic
    chemicals
  ▫ Typically used for treatment of disease
  ▫ Some used for antimicrobial control outside the
    body
                                                          51



Chemical Methods of Microbial Control


• Development of Resistant Microbes
  ▫ Little evidence that products containing antiseptic
    and disinfecting chemicals is beneficial to human
    or animal health
  ▫ Use of such products promotes development of
    resistant microbes
                                                   52




Antimicrobial Agents

• Chemicals that affect physiology in any manner
• Chemotherapeutic agents
 ▫ Drugs that act against diseases
• Antimicrobial agents
 ▫ Drugs that treat infections
                                                       53




The History of Antimicrobial Agents

• Semi-synthetics
 ▫ Chemically altered antibiotics that are more
   effective than naturally occurring ones
• Synthetics
 ▫ Antimicrobials that are completely synthesized in
   a lab
                                                  54



Mechanisms of Antimicrobial Action

• Key is selective toxicity
• Antibacterial drugs constitute largest number
  and diversity of antimicrobial agents
• Fewer drugs to treat eukaryotic infections
  (protozoa, fungi, helminthes)
• Even fewer antiviral drugs
                                                             55



Mechanisms of Antimicrobial Action
• Inhibition of Cell Wall Synthesis
 ▫ Inhibition of bacterial wall synthesis
    Most common agents prevent cross-linkage of NAM
     subunits
    Beta-lactams are most prominent in this group
      Functional groups are beta-lactam rings
      Beta-lactams bind to enzymes that cross-link NAM
       subunits
    Bacteria have weakened cell walls and eventually lyse
                                                       56



Mechanisms of Antimicrobial Action
 • Inhibition of Cell Wall Synthesis
  ▫ Inhibition of synthesis of bacterial walls
     Semi-synthetic derivatives of beta-lactams
         More stable in acidic environments
         More readily absorbed
         Less susceptible to deactivation
         More active against more types of bacteria
     Simplest beta-lactams – effective only against
      aerobic Gram-negatives
                                                         57



Mechanisms of Antimicrobial Action
• Inhibition of Cell Wall Synthesis
 ▫ Inhibition of synthesis of bacterial walls
    Vancomycin and cycloserine
      Interfere with particular bridges that link NAM
       subunits in many Gram-positives
    Bacitracin
      Blocks secretion of NAG and NAM from cytoplasm
      Effective against Gram positives
    Isoniazid and ethambutol
      Disrupt mycolic acid formation in mycobacterial
       species
                                                      58




Mechanisms of Antimicrobial Action
• Inhibition of Cell Wall Synthesis
 ▫ Inhibition of synthesis of bacterial walls
    Prevent bacteria from increasing amount of
     peptidoglycan
    Have no effect on existing peptidoglycan layer
    Effective only for growing cells
                                                      59




Mechanisms of Antimicrobial Action

• Inhibition of Protein Synthesis
 ▫   Prokaryotic ribosomes are 70S (30S and 50S)
 ▫   Eukaryotic ribosomes are 80S (40S and 60S)
 ▫   Drugs can selectively target translation
 ▫   Mitochondria of animals and humans contain 70S
     ribosomes
      Can be harmful
                                                    60




Mechanisms of Antimicrobial Action

• Inhibition of Protein Synthesis
 ▫ Aminoglycosides: excellent against Gram negatives,
   partially effective against Gram positives
      amikacin (Amikin®)
      gentamicin (Garamycin®)
      kanamycin (Kantrex®)
      neomycin (Mycifradin®)
      streptomycin
      tobramycin (TOBI Solution®, TobraDex®)
                                                    61


Antimicrobial inhibition of protein
synthesis




                                      Figure 10.4
                                                        62



Mechanisms of Antimicrobial Action
• Disruption of Cytoplasmic Membranes
  ▫ Some drugs form channel through cytoplasmic
    membrane and damage its integrity
  ▫ Amphotericin B attaches to ergosterol in fungal
    membranes
     Humans somewhat susceptible because cholesterol
      similar to ergosterol
     Bacteria lack sterols; not susceptible
                                                          63



Mechanisms of Antimicrobial Action
 • Disruption of Cytoplasmic Membranes
  ▫ Azoles and allyamines inhibit ergosterol synthesis
  ▫ Polymyxin disrupts cytoplasmic membranes of
    Gram-negatives
     Oral form is toxic to human kidneys, so only used
      topically
  ▫ Some parasitic drugs act against cytoplasmic
    membranes
                                                                                64




Which topical ointment is best?
• Neomycin is an aminoglycoside antibiotic (disrupts protein synthesis). It
  has excellent activity against Gram-negative bacteria, and has
  partial activity against Gram-positive bacteria.

• Polymixin disrupts bacterial cell membranes by interacting with its
  phospholipids. They are selectively toxic for Gram-negative bacteria.

• Bacitracin disrupts cell wall synthesis. Its action is on Gram-positive
  organisms. It can cause contact dermatitis and cross-reacts with allergic
  sensitivity to sulfa-drugs.

• Which topical ointment is best: Neomycin or Triple Antibiotic (contains all
  three)
                                                   65



Mechanisms of Antimicrobial Action
• Inhibition of Metabolic Pathways
  ▫ Antimetabolic agents can be effective when
    pathogen and host metabolic processes differ
  ▫ Quinolones interfere with the metabolism of
    malaria parasites
  ▫ Heavy metals inactivate enzymes
  ▫ Some agents disrupt glucose uptake by many
    protozoa and parasitic worms
  ▫ Some drugs block activation of viruses
                                                         66



Mechanisms of Antimicrobial Action
• Inhibition of Metabolic Pathways
 ▫ Antiviral agents can target unique aspects of viral
   metabolism
    Amantadine, rimantadine, and weak organic bases
     prevent viral uncoating
 ▫ Protease inhibitors interfere with an enzyme that
   HIV needs in its replication cycle
                                                        67



Mechanisms of Antimicrobial Action

• Inhibition of Nucleic Acid Synthesis
 ▫ Several drugs block DNA replication or mRNA
   transcription
 ▫ Drugs often affect both eukaryotic and prokaryotic
   cells
 ▫ Not normally used to treat infections
 ▫ Used in research and perhaps to slow cancer cell
   replication
                                                            68



Mechanisms of Antimicrobial Action

• Inhibition of Nucleic Acid Synthesis
 ▫ Nucleotide analogs
    Interfere with function of nucleic acids
    Distort shapes of nucleic acid molecules and prevent
     further replication, transcription, or translation
    Most often used against viruses
    Effective against rapidly dividing cancer cells
                                   69




Nucleotides and some
of their antimicrobial
analogs

                     Figure 10.7
                                                                                70



Acyclovir
 • Acyclovir is used to decrease pain and speed the healing of herpes sores or
   blisters in people who have varicella (chickenpox), herpes zoster (shingles;
   a rash that can occur in people who have had chickenpox in the past), and
   first-time or repeat outbreaks of genital herpes (a herpes virus infection
   that causes sores to form around the genitals and rectum from time to
   time).
 • Acyclovir is also sometimes used to prevent outbreaks of herpes sores in
   people who are infected with the virus.
 • Acyclovir disrupts nucleic acid function. It works by stopping the spread of
   the herpes virus in the body. Acyclovir will not cure herpes or protect others
   from catching it.
                                                          71


Mechanisms of Antimicrobial Action
• Inhibition of Nucleic Acid Synthesis
  ▫ Quinolones and fluoroquinolones
    Act against prokaryotic DNA gyrase (enzyme that is
     needed for DNA to unwind during replication)
  ▫ Inhibitors of RNA polymerase (enzyme used
    during transcription)
  ▫ Reverse transcriptase inhibitors
    Act against an enzyme HIV uses in its replication
     cycle
    Does not harm people because humans lack reverse
     transcriptase
                                                      72



Mechanisms of Antimicrobial Action

• Prevention of Virus Attachment
 ▫ Attachment antagonists block viral attachment or
   receptor proteins
 ▫ New area of antimicrobial drug development
                                                        73



Clinical Considerations in Prescribing
Antimicrobial Drugs
• Ideal Antimicrobial Agent
  ▫ Readily available
  ▫ Inexpensive
  ▫ Chemically stable
  ▫ Easily administered
  ▫ Nontoxic and nonallergenic
  ▫ Selectively toxic against wide range of pathogens
                                                               74



Clinical Considerations in Prescribing
Antimicrobial Drugs
• Spectrum of Action
  ▫ Number of different pathogens a drug acts against
    Narrow-spectrum effective against few organisms
    Broad-spectrum effective against many organisms
      May allow for secondary or superinfections to develop
      Killing of normal flora reduces microbial antagonism
                                                75


Spectrum of action for selected
antimicrobial agents




                                  Figure 10.8
                                               76



Clinical Considerations in Prescribing
Antimicrobial Drugs
• Efficacy
  ▫ Ascertained by
    Diffusion susceptibility test
    Minimum inhibitory concentration test
    Minimum bactericidal concentration test
                                               77


Diffusion Susceptibility Test:
Zone of inhibition




                                 Figure 10.9
                                                78


Minimum inhibitory concentration test




                                 Figure 10.10
                                               79


A minimum bactericidal concentration
test




                                Figure 10.12
                                                          80


Clinical Considerations in Prescribing
Antimicrobial Drugs
 • Routes of Administration
  ▫ Topical application of drug for external infections
  ▫ Oral route requires no needles and is self-
    administered
  ▫ Intramuscular administration delivers drug via
    needle into muscle
  ▫ Intravenous administration delivers drug directly
    to bloodstream
  ▫ Must know how antimicrobial agent will be
    distributed to infected tissues
                                    81




               Effect of route of
               administration on
               chemotherapeutic
               agent




Figure 10.13
                                                          82


Clinical Considerations in Prescribing
Antimicrobial Drugs
• Safety and Side Effects
  ▫ Toxicity
     Cause of many adverse reactions poorly understood
     Drugs may be toxic to kidneys, liver, or nerves
     Consideration needed when prescribing drugs to
      pregnant women
  ▫ Allergies
     Allergic reactions are rare but may be life
      threatening
     Anaphylactic shock
                                                  83


Side effects resulting from toxicity of
antimicrobial agents




                                   Figure 10.14
                                                          84



Clinical Considerations in Prescribing
Antimicrobial Drugs

• Safety and Side Effects
  ▫ Disruption of normal microbiota
    May result in secondary infections
    Overgrowth of normal flora causing superinfections
    Of greatest concern for hospitalized patients
                                                        85




Resistance to Antimicrobial Drugs
• The Development of Resistance in
  Populations
  ▫ Some pathogens are naturally resistant
  ▫ Resistance by bacteria acquired in two ways
    New mutations of chromosomal genes
    Acquisition of resistance genes (R-plasmids) via
     transformation, transduction, and conjugation
                                                86




The development of a resistant strain
of bacteria




                                 Figure 10.15
                                                             87



Resistance to Antimicrobial Drugs
• Mechanisms of Resistance
 ▫ At least six mechanisms of microbial resistance
    Production of enzyme that destroys or deactivates
     drug
    Slow or prevent entry of drug into the cell
    Alter target of drug so it binds less effectively
    Alter their metabolic chemistry
    Pump antimicrobial drug out of the cell before it can
     act
    Mycobacterium tuberculosis produces MfpA protein
      Binds DNA gyrase preventing the binding of
       fluoroquinolone drugs
                                               88




How -lactamase renders penicillin
inactive




                                Figure 10.16
                                                        89




Resistance to Antimicrobial Drugs
• Multiple Resistance and Cross Resistance
 ▫ Pathogen can acquire resistance to more than one
   drug
 ▫ Common when R-plasmids exchanged
 ▫ Develop in hospitals and nursing homes
    Constant use of drugs eliminates sensitive cells
 ▫ Superbugs
 ▫ Cross resistance
                                                               90



Resistance to Antimicrobial Drugs

• Retarding Resistance
 ▫ Maintain high concentration of drug in patient for
   sufficient time
    Kills all sensitive cells and inhibits others so immune
     system can destroy
 ▫ Use antimicrobial agents in combination
    Synergism vs. antagonism
                                             91


Example of synergism between two
antimicrobial agents




                              Figure 10.17
                                                      92



Resistance to Antimicrobial Drugs
• Retarding Resistance
 ▫ Use antimicrobials only when necessary
 ▫ Develop new variations of existing drugs
    Second-generation drugs
    Third-generation drugs
 ▫ Search for new antibiotics, semi-synthetics, and
   synthetics
    Bacteriocins
    Design drugs complementary to the shape of
     microbial proteins to inhibit them
                                                              93

Vaccination
• Vaccine – use the immune system to protect
  against infectious disease
• Types of vaccines
 ▫ attenuated (weakened) microbe; virulence factors are
   removed
 ▫ heat-killed / chemically killed microbe
 ▫ toxoids
• Passive versus Adaptive vaccination
 ▫ passive – immune system products from another
    mothers milk (presence of IgA)
    gamma-globulin (anti-bee venom, anti-hepatitis A, etc)
 ▫ active – stimulate individuals immune system to produce
   memory cells
                                  94

 Effect of smallpox vaccine




Initial “modern” vaccine: 1796.
                              95



U.S. cases
against
diseases for
which there
are vaccines.




SSPE: sub-acute sclerosing
panencephalitis (late stage
measles)
                                               96




• Why Your Cellphone Has More Bacteria
  Than a Toilet Seat
• By Susan E. Matthews, MyHealthNewsDaily
  Staff Writer | LiveScience.com – 3 hrs ago


• http://news.yahoo.com/why-cellphone-more-
  bacteria-toilet-seat-124147769.html
97

				
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