Transcript The History of Antimicrobial Agents

-cidal or -static
• -cidal means to kill
• Bacteriocidal agent kills bacteria
• -static means to inhibit or prevent
• Bacteriostatic agent will only inhibit or
prevent bacterial growth
Mechanisms of Bacterial Attack
A. Adhesion – how bacteria bind to host.
*2 Basic ways*
1. Pili (Fimbria)
2. Glycocalyx (capsule or slime layer)
B. Bacterial Toxins – poisons released by
certain bacteria.
1.Exotoxins – poisons are released by live bacteria
a. They are tissue specific.
-Example: Hemolysins – Exotoxins that
cause red blood cells to burst
b. Found in some gram+ and gram-
2. Endotoxins- poisons released only when bacteria
lyse (burst)
*Found in all gram- Bacteria
The History of Antimicrobial Agents
• Chemicals that affect physiology in any
manner
• Chemotherapeutic agents
– Drugs that act against diseases
• Antimicrobial agents
– Drugs that treat infections
© 2012 Pearson Education Inc.
The History of Antimicrobial Agents
• Paul Ehrlich
– “Magic bullets”
• Arsenic compounds that killed microbes
• Alexander Fleming
– Penicillin released from Penicillium
• Gerhard Domagk
– Discovered sulfanilamide
• Selman Waksman
– Antibiotics
• Antimicrobial agents produced naturally by organisms
Figure 10.1 Antibiotic effect of the mold Penicillium chrysogenum
Staphylococcus
aureus
(bacterium)
Penicillium
chrysogenum
(fungus)
Zone where
bacterial growth
is inhibited
The History of Antimicrobial Agents
• Semisynthetics
– Chemically altered antibiotics that are more
effective than naturally occurring ones
• Synthetics
– Antimicrobials that are completely synthesized in a
lab
XIII. Controlling Microbes
Method Description
Mode of Action
Used For
A. Open Flame
Stick in hot flame for Combust to Ash
a few seconds
Sterilize tools
B. Incinerator
Furnace with flames
Disposing
hospital waste
Combust
Method Description
Mode of Action
C. Dry Oven Items placed in
Dehydration and denatures
150-180 degree C
oven for 2-4 hours
for 10-40 minutes
Sterilize tools
Proteins
D. Autoclave Steam pressure oven - Destroys CM and DNA
15PSI at 121 degrees C
Used For
- Denatures Proteins
Sterilize tools
(Dentist Office)
Method
Description
Mode of Action
Used For
E. Tyndallization unpressurized
“Intermittent
Sterilization”
-Destroys CM and DNA Items that can’t
steam at 121 degrees C - Denatures proteins tolerate autoclave
-3 days in a row
and food containing
“bibib”
endospores
F.Boiling Water 100 degree C
water bath
G. Pasteurization 1. Batch Method:
64 C for 30 minutes
2.Flash Method:
71 C for 15 seconds
-Destroys DNA and CM Can kill all except
-Denatures proteins
-Destroys DNA and CM
Endospores
Kills many pathogens
that spoil
beverages
Method
Description
H. Cold
Refrigerator or
freezer
I. Irradiation
Exposing items to
X-rays, gamma rays
or cathode rays
Mode of Action
Used For
Slows microbe reproduction Preserving food
Damages DNA
Sterilizes food
Method
Description
Mode of Action
Used For
J. UV Rays
Exposing items to
UV Rays
Damages DNA
disinfects items
“Water-goggles”
K. Filtration
Filtering bacteria
from fluid and air
Physical removal
1. Sterilizes heat
sensitive liquids
such as blood
2. cleans hospital
air
Method
Description
L. Chlorine
Adding chlorine gas
to liquids – “Bleach”
Mode of Action
Denatures proteins
Used For
1. Bleach
2. Chlorine in tapwater
3. Chlorine in pools
M. Iodine
Iodine in solution
Denatures proteins
1. On skin
2. disinfects
Method
N. Alcohol
Description
Mode of Action
Used For
50-95% Ethyl alcohol
70-90% Isopropyl
alcohol
Destroys cell membrane Disinfects surfaces
and tools
O. H2O2
Liquid Hydrogen
Protein and DNA damage
“Hydrogen
Peroxide”
peroxide
also cleans wounds
*also damages CW
disinfects surface
and tools
also cleans wounds
Mechanisms of Antimicrobial Action
• Key is selective toxicity
• Antibacterial drugs constitute largest number
and diversity of antimicrobial agents
• Fewer drugs to treat eukaryotic infections
• Even fewer antiviral drugs
Figure 10.2 Mechanisms of action of microbial drugs
Inhibition of pathogen’s
attachment to, or
recognition of, host
Arildone
Pleconaril
Inhibition of cell
wall synthesis
Penicillins
Cephalosporins
Vancomycin
Bacitracin
Isoniazid
Ethambutol
Echinocandins
(antifungal)
Inhibition of
protein synthesis
Aminoglycosides
Tetracyclines
Chloramphenicol
Macrolides
Human
cell membrane
Inhibition of DNA
or RNA synthesis
Actinomycin
Nucleotide
analogs
Quinolones
Rifampin
Disruption of
cytoplasmic membrane
Polymyxins
Polyenes (antifungal)
Inhibition of general
metabolic pathway
Sulfonamides
Trimethoprim
Dapsone
1. Inhibit Cell Wall synthesis:
– prevent cross-linkage of NAM subunits
– Bacteria have weakened cell walls and eventually lyse
a. Penicillin
b. Cephalosporins
No Folic Acid =
No RNA or
DNA synthesis
3. Inhibit Protein Synthesis (Translation)
*Tetracyclines, Erythromycin, and
Chloramphenicol
– Prokaryotic ribosomes are 70S (30S and 50S)
– Eukaryotic ribosomes are 80S (40S and 60S)
– Mitochondria of animals and humans contain 70S
ribosomes
• Can be harmful
– protein’s denature
4. Damage Cell Membrane.
• form channel through membrane
and damage its integrity
• the cell loses its selective
permeability
• Most are toxic to human cells
• Polymyxins, Polyenes and Imidazoles
are selective for microbe cell
membranes
5. Inhibition of Metabolic
Pathways
• Heavy metals inactivate
enzymes
• effective when metabolic
processes of pathogen and host
differ
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
• act against the pathogen and not the host
Clinical Considerations in Prescribing Antimicrobial Drugs
• Spectrum of Action
– Narrow-spectrum effective against few organisms
• Targets specific aspects or types of bacteria
– Broad-spectrum effective against many organisms
• May allow for secondary or superinfections to develop
• Killing of normal flora reduces microbial antagonism
Figure 10.8 Spectrum of action for selected antimicrobial agents
Determining Susceptibility of
Bacterial to Antimicrobial Drug
• MIC = Minimum Inhibitory Concentration
Determining Susceptibility of
Bacterial to Antimicrobial Drug
• Kirby-Bauer disc diffusion
method
size of clearing zone indicates if
susceptible or resistant
• E-test
– Uses strips with gradient concentration of antibiotic
– Test organism will grow and form zone of inhibition
• Zone is tear-drop shaped
• Zone will intersect strip at inhibitory concentration
Figure 10.11 An Etest combines aspects of Kirby-Bauer and MIC tests
Clinical Considerations in Prescribing Antimicrobial Drugs
• Safety and Side Effects
– Disruption of normal microbiota
• May result in secondary infections
• Overgrowth of normal flora causes superinfections
• Of greatest concern for hospitalized patients
Bacteria and Antibiotics Resistance
*How do Bacteria Resistant Bacteria Form?
Step 1- Variations exist (In DNA) among members
of all species. -Including drug resistant traits
(usually in plasmid DNA)
Acquisition of R-plasmids via transformation, transduction, and
conjugation
Step 2- Bacteria Exposed to Antibiotic
Step 3- All Bacteria die except
the ones with the resistant gene
Step 4- Ab. Resistant Bacteria
Flourish without many competitors
• Multiple 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
Methicillin-resistant Staphylococcus
aureus (MRSA)
• a strain of bacteria that's become resistant to the
antibiotics
– hospitals
– invasive procedures or devices, such as surgeries,
intravenous tubing or artificial joints
• Another type of MRSA infection has occurred in
the wider community — among healthy people
– often begins as a painful skin boil
– It's spread by skin-to-skin contact
– high school wrestlers, child care workers and people
who live in crowded conditions
*Which Antibiotic are least effective?
>Older ones like Penicillin<
**Why are new antibiotics still made?
>To keep up with evolving bacteria<
>> Vancomycin ……….Zyvox<<
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
Figure 10.17 An example of synergism between two antimicrobial agents
Disk with semisynthetic
amoxicillin–clavulanic acid
Disk with semisynthetic
aztreonam
Resistance to Antimicrobial Drugs
• Retarding Resistance
– Use antimicrobials only when necessary
– Develop new variations of existing drugs
• Second and third -generation drugs
– Search for new antibiotics, semisynthetics, and
synthetics
• Design drugs complementary to the shape of microbial
proteins to inhibit them
Chemical METHODS OF DISINFECTION
• Heavy metals (Ag, Hg, Cu)
• Silver is an antimicrobial agent
• Used in dressings for burn victims
• Incorpotated into indwelling catheters
– CuSO4 used to destroy green algae in swimming
pools and fish tanks
– Cu + Zn treated shingles are available to create
anti-fungal roofs
– ZnCl2 is common ingredient in mouthwash
Chemical Food Preservatives
• SO2 (wine)
• Na-benzoate, Ca-propionate, sorbic acid
(cheese, soft drinks, breads)
• NaNO3 or NaNO2 (ham, bacon, hot dogs)
–Very effective against Clostridium botulinum
Chemical Food Preservative
•Nabenzoate in coke/cheese prevents growth of
molds
•Foods w/ low pH tend to be susceptible to
mold
•NaNO3/NO2 are added to meat products (ham,
bacon, hot dogs etc.)
•Salts prevents growth of some types of
bacteria that are responsible for meat spoilage
Nitrates/Nitrites
•NaNO3/NO2 are added to meat products (ham,
bacon, hot dogs etc.)
•Salts prevents growth of some types of
bacteria that are responsible for meat spoilage
Nitrates in food
Nitrite in meat greatly delays the development of
botulinal toxin (botulism)
Sugar is added to cured meats as well to reduce
the harshness of salts
Sodium nitrite (NaNO2), rather than sodium nitrate
(NaNO3), is commonly used for curing
NO2 is converted to Nitric oxide
Nitric oxide combines with myoglobin (responsible
for the natural red color of uncured meat)