-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. tissue specific
i.e. Hemolysins – 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 negative 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
• Semisynthetics– Chemically altered antibiotics that are more effective
than naturally occurring ones
• Synthetics– Antimicrobials that are completely synthesized in a lab
© 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
Controlling MicrobesMethod Description Mode of Action Used For
A. Open Flame Stick in hot flame for Combust to Ash Sterilize tools
a few seconds
B. Incinerator Furnace with flames Combust Disposing hospital waste
Method Description Mode of Action Used For
C. Dry Oven Items placed in Dehydration and denatures Sterilize tools150-180 degree C Proteins
oven for 2-4 hours
D. Autoclave Steam pressure oven - Destroys CM and DNA Sterilize tools
15PSI at 121 degrees C - Denatures Proteins (Dentist Office)
for 10-40 minutes
Method Description Mode of Action Used ForE. Tyndallization unpressurized -Destroys CM and DNA Items that can’t “Intermittent steam at 121 degrees C - Denatures proteins tolerate autoclave
Sterilization” -3 days in a row and food containing “bibib” endospores
F.Boiling Water 100 degree C -Destroys DNA and CM Can kill all except
water bath -Denatures proteins Endospores
G. Pasteurization 1. Batch Method: -Destroys DNA and CM Kills many pathogens
64 C for 30 minutes that spoil beverages
2.Flash Method:
71 C for 15 seconds
Method Description Mode of Action Used ForH. Cold Refrigerator or Slows microbe reproduction Preserving food
freezer
I. Irradiation Exposing items to Damages DNA Sterilizes food
X-rays, gamma rays
or cathode rays
Method Description Mode of Action Used ForJ. UV Rays Exposing items to Damages DNA disinfects items
UV Rays “Water-goggles”
K. Filtration Filtering bacteria Physical removal 1. Sterilizes heat
from fluid and air sensitive liquids
such as blood
2. cleans hospital air
Method Description Mode of Action Used ForL. Chlorine Adding chlorine gas Denatures proteins 1. Bleach
to liquids – “Bleach” 2. Chlorine in tapwater
3. Chlorine in pools
M. Iodine Iodine in solution Denatures proteins 1. On skin
2. disinfects
Method Description Mode of Action Used ForN. Alcohol 50-95% Ethyl alcohol Destroys cell membrane Disinfects surfaces
70-90% Isopropyl and tools
alcohol also cleans wounds
O. H2O2 Liquid Hydrogen Protein and DNA damage disinfects surface
“Hydrogen peroxide *also damages CW and tools
Peroxide” 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
Humancell membrane
Inhibition of pathogen’sattachment to, orrecognition of, hostArildonePleconaril
Inhibition of cellwall synthesisPenicillinsCephalosporinsVancomycinBacitracinIsoniazidEthambutolEchinocandins(antifungal)
Inhibition of DNAor RNA synthesisActinomycinNucleotide
analogsQuinolonesRifampin
Inhibition of generalmetabolic pathwaySulfonamidesTrimethoprimDapsone
Disruption ofcytoplasmic membranePolymyxinsPolyenes (antifungal)
Inhibition ofprotein synthesisAminoglycosidesTetracyclinesChloramphenicolMacrolides
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
Narrow vs. Broad Spestrum
– 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– 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
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 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
• Slow down 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
Resistance to Antimicrobial Drugs
• Delaying 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)