Antimicrobials 1

Question 1

6 MAJOR groups of antimicrobials (there are others too):

Answer 1

1. Beta-Lactams
2. Aminoglycosides
3. Tetracyclines
4. Sulfonamides
5. Macrolides
6. Fluoroquinolones

Others: Chloramphenicol, rifampin, metronidazole, clindamycin, etc.

Question 2

bacteriocidal vs bacteriostatic

Answer 2

Bactericidal: a drug that kills bacteria independent of host immune function

Bacteriostatic: a drug that inhibits bacterial growth and division; immune system can then more rapidly eradicate the non-multiplying bacteria

Question 3

why are label directions important for antimicrobials?

Answer 3

Some antimicrobials approved for one species can be lethal in another, and some drugs that are safe to give by one route of administration can kill if given by another.

Question 4

time vs concentration dependent AMDs

Answer 4

Time-dependent AMDs:
Efficacy is associated with length of time drug concentration remains above MIC
>Levels should remain above MIC throughout course of therapy

Concentration-dependent AMDs:
Efficacy depends on peak concentration (may be well in excess of MIC)
>Not necessary to maintain levels above MIC for the entire interval between doses

Question 5

what route of administration do we generally avoid in ruminants and why?

Answer 5

Antimicrobial drugs are not administered orally to ruminants
* They may be destroyed in the rumen, or
* They may destroy rumen microflora causing rumen stasis

It is acceptable to give AMDs by the oral route to pre-ruminant calves

Question 6

what do we have to be cautious of in terms of route of administration of antimicrobials for hind-gut fermenters?

Answer 6

Some drugs that are safe to administer parenterally will, if given orally, trigger the release of toxins from gut bacteria
* These toxins may be lethal

Question 7

is drug resistance an all-or-nothing characteristics? why or why not?

Answer 7

it is not:
* Each infection contains a mix of bacteria of different sensitivities; therapy may leave the most resistant
* Different strains of the same bacterium from different patients may differ in sensitivity to a given drug, even in the same geographic area

Question 8

sulfonamides main mechanism of action

Answer 8

Inhibition of folic acid synthesis

Question 9

many antifungals use this mechanism of action

Answer 9

damage to plasma membrane

Question 10

beta-lactams mechanism of action

Answer 10

Inhibition of cell wall synthesis

Question 11

which main classes of antimicrobials work by inhibiting protein synthesis?

Answer 11

Aminoglycosides
Tetracyclines
Macrolides

Question 12

what is the mechanism of action of fluoroquinolones?

Answer 12

damage to DNA

Question 13

Determination of Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) by serial drug dilution:

Answer 13

• To determine MIC, serial 1:2 dilutions of an antimicrobial drug are added to tubes containing bacterial growth medium (usually expressed in μg/mL)
• Each tube is then seeded with a standard quantity of bacteria
• After a set time (usually 24 h) the tubes are assessed for visible bacterial growth (turbidity of the growth medium)
• The tube showing no turbidity at lowest drug concentration is designated the MIC (No visible growth, but bacteria may be alive)
• By culturing samples from each tube in drug-free medium, the MBC can be determined (the drug concentration that sterilized the tube, resulting in no growth in this step)

Question 14

what does the Kirby-Bauer test do?

Answer 14

Kirby-Bauer disk diffusion test;
Antibacterial drug susceptibility testing:
* Paper disks impregnated with different drugs placed on plate uniformly swabbed with bacteria
> drugs diffuse into agar
* Zone of inhibition around each disk measured after specified time and compared to a regression curve

> reported as Sensitive, Intermediate, or Resistant to the drug

Question 15

Principles for Selecting & Administering Antimicrobial Drugs

Answer 15

1. If possible, identify the organism
   * Gram & other stains; cytology
   * Knowledge of the most common pathogens at the site
   => Culture & sensitivity testing for serious infections
2. Select a drug. Consider:
   * Bacterial sensitivity
   * Bacteriostatic vs. bactericidal
   * Adverse effects
   * Distribution
   * Cost
3. Dosage
   * Use label recommendations, or consult a reference text
4. Initiate treatment ASAP
5. Food safety
   * Use approved drugs according to the label directions unless you have good grounds for going off-label
   * Adhere to withdrawal times

Question 16

What considerations do we have to make regarding bacterial sensitivity to drugs when selecting an antimicrobial for use? why?

Answer 16

Use narrow-spectrum drugs when possible, to avoid selecting for AMD- resistant commensal bacteria

Question 17

when do we want to choose a bactericidal drug over a bacteriostatic drug?

Answer 17

Want bactericidal drug if immune system compromised, or infection is life- threatening

Question 18

what two anatomic locations is it difficult for antimicrobials to enter?

Answer 18

CNS and prostate

Question 19

disease processes requiring special consideration for antimicrobial use:

Answer 19

osteomyelitis
foreign body
implants
abscess
intracellular pathogens
dysfunctional host defences

Question 20

why is osteomyelitis an annoying condition to treat with AMDs? what issues can arise?

Answer 20

Avascular bone fragments can provide a site in which bacteria can avoid exposure to AMD
>source of bacteria for reinfection

Question 21

if we are dealing with an intracellular pathogen, the antimicrobial we select should be able to:

Answer 21

enter cells readily

Question 22

in what situations does prophylactic use of antimicrobials make sense?

Answer 22

Medical
a) High risk of serious infection following trauma
- e.g., meningitis, mastitis, cellulitis
b) Patient’s condition will allow a serious infection
- E.g., immune system defects

Surgical
>goal is to have adequate AMD levels in tissue at time of incision

Question 23

Appropriate AMD selection requires knowledge of:

Answer 23

• General spectrum of activity
• Mechanism of action
• Major adverse effects
• Distribution / elimination
• “First line”, “second line”, or emergency classification
• Possible routes of administration
• Cost