CHP 14- ANTIMICROBIAL THERAPY

Any chemical agent used to treat any disease

chemotherapy

chemical agents used to treat diseases caused by microbes

antimicrobial therapy

chemical substances produced by microorganisms which has the capacity to inhibit the growth of bacteria

antibiotic

chemical agent produced in a laboratory

synthetic drugs

anything taken internally/harms microbes without damage to host cells (dose, exposure, metabolism); if an antimicrobial agent is toxic to take systemically (used topically or on skin)

selective toxicity

Side effects

toxicity and allergy

can affect normal host tissues, such as the liver

toxicity

host immune system/treats drug as foreign (penicillin)

allergy

normal microflora inhabit the skin, digestive, respiratory, and urogenital tracts

killed off = other microbes can take over/invade their area (SUPERINFECTION)

disruption of microflora

The microbe used to be susceptible to an antibiotic no longer affected by it

-make genetic changes

-change to "L" form/stop making a cell wall

-evade antibiotics by "hiding" in tissues

resistance of microorganisms

What are the mechanisms of resistance?

Alt of target, Alt of membrane permeability, development of enzymes, alteration of an enzyme, alteration of a metabolic pathway

What is the ideal of an antimicrobial agent?

-Soluble body fluids

-Toxicity NOT altered by foods, other drugs, or diseases in the host

-Selective toxicity

-Stable over many hours

-Few strains resistant to it

-Long shelf life

-Cost-effective

-Patient compliance

resistance to two or more antimicrobial agents because they share a common mechanism.

cross resistance

A mutation in DNA changes a protein so that an antibiotic no longer binds to it

Alt of the targets

A mutation in DNA changes the membrane so that the antibiotic no longer penetrates the cell

Alt of Membrane permeability

New enzyme breaks down as an antibiotic

Development of an Enzyme

Change in some way to function even in the presence of a noncompetitive inhibitor

Alt of an Enzyme

Bacteria can pass through a metabolic pathway inhibited by an antibiotic

Alt of a Metabolic Pathway

The first drug used to treat microbial infection, as new resistant strains evolve, there may be a need for a 2nd, 3rd, etc

First-line drug

What are the modes of action?

1. Inhibition of cell wall synthesis

2. Disruption of cell membrane function

3. Inhibition of protein synthesis

4. Inhibition of nucleic acid synthesis

5. Action as antimetabolites

Inhibition of cell wall synthesis

penicillin

Disruption of cell membrane function

Polymyxin

work on bacteria/gram-negative

Polymyxin

work on fungal cells

polyenes

Inhibition of protein synthesis

Aminoglycoside antibiotics (streptomycin and erythromycin)

Inhibition of nucleic acid synthesis

Rifamycin binds to RNA polymerase

Ametabolites

competitive inhibitors of enzymes

How do we test microbes for sensitivity to antimicrobial agents?

-Disk Diffusion

-Dilution method

-Serum killing power

-Automated Methods

Filter paper disks with different concentrations of antimicrobial agents are placed on agar containing a known microbe.

(Clear areas around disks indicate that it inhibited the microbe)

Disk Diffusion

organism inoculated into broth in a culture dish w/many wells; decreasing concentrations of antimicrobial agent added to wells.

Dilution method

uses blood from a patient receiving antimicrobial therapy; the microbe is added to the patient's serum/measured for growth.

Serum killing power

Trays w/ wells support the growth of a variety of microbes.

Automated Methods