1. -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

2. Mechanisms of Bacterial Attack
Adhesion – how bacteria bind to host.
*2 Basic ways*
1. Pili (Fimbria)
2. Glycocalyx (capsule or slime layer)

3. 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-

4. 2. Endotoxins- poisons released only when bacteria lyse (burst)
*Found in all gram- Bacteria

7. 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. 7

8. 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 8

9. Figure 10.1 Antibiotic effect of the mold Penicillium chrysogenum
Staphylococcus aureus (bacterium)
Penicillium chrysogenum (fungus)
Zone where bacterial growth is inhibited

10. 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 10

11. XIII. Controlling Microbes
Method 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

12. Method Description Mode of Action Used For
C. Dry Oven Items placed in Dehydration and denatures Sterilize tools
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 minutes

13. Method Description Mode of Action Used For
E. 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

14. Method Description Mode of Action Used For
H. 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

15. Method Description Mode of Action Used For
J. UV Rays Exposing items to Damages DNA disinfects items
UV Rays “Water-goggles”
K. Filtration Filtering bacteria Physical removal Sterilizes heat
from fluid and air sensitive liquids
such as blood
2. cleans hospital air

16. Method Description Mode of Action Used For
L. Chlorine Adding chlorine gas Denatures proteins Bleach
to liquids – “Bleach” Chlorine in tapwater Chlorine in pools
M. Iodine Iodine in solution Denatures proteins On skin
2. disinfects

17. Method Description Mode of Action Used For
N. Alcohol % Ethyl alcohol Destroys cell membrane Disinfects surfaces
70-90% Isopropyl and tools
alcohol also cleans wounds
O. H2O Liquid Hydrogen Protein and DNA damage disinfects surface
“Hydrogen peroxide *also damages CW and tools
Peroxide” also cleans wounds

18. 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 18

20. Figure 10.2 Mechanisms of action of microbial drugs
Inhibition of cell wall synthesis
Penicillins
Cephalosporins Vancomycin
Bacitracin
Isoniazid
Ethambutol
Echinocandins (antifungal)
Inhibition of pathogen’s attachment to, or recognition of, host
Arildone Pleconaril
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

22. Inhibit Cell Wall synthesis:
prevent cross-linkage of NAM subunits
Bacteria have weakened cell walls and eventually lyse
a. Penicillin
b. Cephalosporins

23. No Folic Acid = No RNA or DNA synthesis

24. 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

25. 5. Inhibition of Metabolic Pathways
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

26. 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 26

27. 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 27

28. Figure 10.8 Spectrum of action for selected antimicrobial agents

29. Determining Susceptibility of Bacterial to Antimicrobial Drug
MIC = Minimum Inhibitory Concentration

30. Determining Susceptibility of Bacterial to Antimicrobial Drug
Kirby-Bauer disc diffusion method
size of clearing zone indicates if susceptible or resistant

31. 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

32. Figure 10.11 An Etest combines aspects of Kirby-Bauer and MIC tests

33. 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 33

34. 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

35. Step 3- All Bacteria die except the ones with the resistant gene Step 4- Ab. Resistant Bacteria Flourish without many competitors

36. 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 36

37. 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

42. Which Antibiotic are least effective
*Which Antibiotic are least effective? >Older ones like Penicillin< **Why are new antibiotics still made? >To keep up with evolving bacteria< >> Vancomycin ……….Zyvox<<

43. 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 43

44. Figure 10.17 An example of synergism between two antimicrobial agents
Disk with semisynthetic amoxicillin–clavulanic acid
Disk with semisynthetic aztreonam

45. 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 45

46. 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

47. 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

48. 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

49. 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

50. 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)