Chap 12 Antimicrobial Therapy

Selective Toxicity

• Development and use of drugs that targets microbe w/out targeting and damaging the host.

• Made by microbes that target microbes

Prophylaxis

Use drug to prevent infection for a person at risk

Selective Toxicity

• Development and use of drugs that targets microbe w/out targeting and damaging the host.

• Made by microbes that target microbes

Prophylaxis

Use drug to prevent infection for a person at risk

Discovery of antibiotics

Alexander Fleming (1928), discovery Penicillin from Penicillium species of fungus

Antibiotic made from

Bacteria and Fungi

Kirby-Bauer test

To see how affected drug are on certain microbes.

Bigger circles = more susceptible

Smaller circles = less susceptible

Broad spectrum drug

Effective against more than 1 group of bacteria

ex) tetracyclines

Narrow spectrum drugs

Only target a specific group

ex) polymyxin and penicillins

Isoniazid target

Mycobacteria

Streptomycin target

Mycobacteria

Gram negative bacteria

Tobramycin target

Mycobacteria

Polymyxin target

Mycobacteria

Gram negative bacteria

Carbapenems target

Mycobacteria

Gram-negative bacteria

Gram-positive bacteria

Tetracyclines target

Gram-negative bacteria

Gram-positive bacteria

Chlamydias

Rickettsias

Sulfonamides Cephalosporins target

Gram-negative bacteria

Gram -positive bacteria

Penicillin target

Gram-negative bacteria

Gram-positive bacteria

Chlamydias

Protein synthesis inhibitors

Erythromycin

Clindamycin

Aminoglycosides

Tetracyclines

Cell Wall Inhibitor

Penicillin

Cephalosporins

Bacitracin

Vancomycin

Cell Membrane inhibitors

Polymyxins

Nucleic acid inhibitors

Fluoroquinolones

Rifampin

Folic Acid synthesis inhibitors

Sulfonamides

Trimethoprim

Penicillins

• History: uses to treat syphilis, Staphylococcus, Streptococcus.

• Block cross-link of peptidoglycan (only new cell wall are affected)

Drug Resistance

Intrinsic: bacteria must resistant to any antibiotic that they themselves created.

Accquired: bacterial resistance to drug that been previously exposes to

Instrinsic mechanism

Resistance through spontaneous mutation

Acquired mechanism

Resistance through horizontal transfer

Mechanisms of Horizontal Gene Transfer

Conjugation: DNA fragments “plasmid” transferred through pilus

Transformation: Uptake DNA from surrounding environment

Transduction: Introduction of DNA via phage/virus infection of bacteria

Transposons: DNA sequences move to different locations (within genomes or onto plasmid)

How drug resistance genes cause resistance

• New enzymes are synthesized: inactivated drug and occur when new genes are acquired

• Permeability/uptake of drug into bacterium is decreased: via mutation

• Drug is immediately eliminated: via acquisition of new genes

• Binding sites for drug decreased: via mutation/acquisition of new genes.

• Affected metabolic shut down/alternative pathway is used: mutation of og enzyme

Prevent drug resistance

Limit drug use

Proper drug use

Narrow range antibiotics

Multiple drug treatments

New Approaches for bacteria antibiotic

Probiotic: introduced live microbes from food/oral supplements

Prebiotics: nutrients that encourage growth of beneficial microbes

Bacteriophage: target specific bacterial species.

Interaction btw drug and host

Organ toxicity:

• nephrotoxic “kidney”

• hepatoxic “liver”

• hematoxic

• Gl

• cardio toxicities

• neurotoxic

• respiratory

• skin, bones, teeth

Loss of normal flora:

• Yeast infection

• Clostridium difficile

Allergic Responses