-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)