Testing for drug susceptibility

Question 1

Describe the Tube dilution tests:

Answer 1

• More sensitive and quantitative than the Kirby-Bauer test
• Antimicrobial is diluted serially in tubes of broth.
  -Each tube is inoculated with a small uniform sample of pure culture.
  -Minimum inhibitory concentration (MIC): the smallest concentration (highest dilution) of drug that visibly inhibits growth
  Useful in determining the effective dosage and providing a comparative index against other antimicrobials

Question 2

The MIC: In vitro activity of a drug is not always correlated with the in vivo effect

Failure of antimicrobial treatment is due to

Answer 2

• The inability of the drug to diffuse into that body compartment (brain, joints, skin)
• Resistant microbes in the infection that didn’t make it into the sample collected for testing
• An infection caused by more than one pathogen (mixed), some of which are resistant to the drug

Question 3

Therapeutic Index definition
What does smaller ratio mean
Which is the risky choice and what is the safer choice?

Answer 3

Therapeutic index: the ratio of the dose of the drug that is toxic to humans as compared to its minimum effective (therapeutic) dose:
The smaller the ratio, the greater the potential for drug reactions
TI = 1.1 is a risky choice
TI = 10 is a safer choice
The drug with the highest therapeutic index has the widest margin of safety.

Question 4

The physician must take a careful history before prescribing an antibiotic:

Answer 4

Preexisting conditions that might influence the activity of the drug
History of allergy to a certain class of drugs
Underlying liver or kidney disease
Infants, the elderly, and pregnant women require special precautions
Intake of other drugs can result in increased toxicity or failure of one or more drugs
Genetic or metabolic abnormalities
Site of infection, route of administration, cost

Question 5

Goal of antimicrobial drugs on a microbe

Answer 5

Disrupt cell processes or structures of bacteria, fungi, or protozoa
Inhibit virus replication
Interfere with the function of enzymes required to synthesize or assemble macromolecules
Destroy structures already formed in the cell

Question 6

kill or inhibit the actions or synthesis of molecules in microorganisms but not vertebrate cells

Answer 6

selectively toxic

Question 7

Drugs with excellent selective toxicity block the synthesis of the_________

Answer 7

Drugs with excellent selective toxicity block the synthesis of the bacterial cell wall (penicillins).
Human cells lack the chemical peptidoglycan and are unaffected by the drug.

Question 8

What makes drugs most toxic to humans?

Answer 8

Drugs that act upon a structure common to both the infective agent and the host cell (cell membrane)
As characteristics of the infectious agent are more and more similar to the host cell, selective toxicity becomes more difficult to achieve

Question 9

Goals of chemotherapy

Answer 9

identifying structural and metabolic needs of a living cell and removing, disrupting, or interfering with these requirements

Question 10

What are the antimicrobial drug categories

Answer 10

-Inhibition of cell wall synthesis
-Inhibition of nucleic acid structure and function
- Inhibition of protein synthesis
-Interference with cell membrane structure and function
-Inhibition of folic acid synthesis