Why is the disk-diffusion technique not a perfect indication of how the drug will perform in vivo?

Question

What other factors are considered before using the antimicrobial agent in vivo?

Answer 1

The human body is not an agar gel plate but a complex environment that may alter the desired outcome of delivery of the drug to the site of action:

Absorption / route of administration and site of infection
Vancomycin is a great antibiotic and kills lots of stuff. Give it orally for a systemic infection and it won't be absorbed! Give it intravenously for pseudomembranous colitis and it won't get into the GIT to affect the clostridia.

Otitis externa and external ocular infections are best treated with topical antibiotics rather than systemic antibiotics.

Topical antibiotics are not likely to penetrate an intact ear drum to reach an otitis media.

(First pass) Metabolism
Orally administered drugs absorbed from the GIT have to go through the liver which usually gets first shot at messing about with them. Some drugs take advantage of this and are given as prodrugs which are metabolized to the active form. Other drugs are metabolized to an inactive form by the liver and then excreted.

Organism defence
One of the classic ways bacteria can protect themselves is by formation of an abscess. A thick walled cyst containing bacteria and pus inside, but walled off from the rest of the body by inflamed connective tissue - this can be difficult for antibiotics to penetrate and may require surgical excision and drainage.

Drug resistance - organisms in the human body interact with other organisms, eg bacterial flora in the gut. They can exchange plasmids encoding proteins that will promote bacterial resistance to the antibiotics.

Other factors
Patient intolerance to drug: drug side effects / allergy / anaphylaxis

Drug interactions: patients may be on other medications which would make it undesirable to administer that antibiotic (eg. giving erythromycin to patients taking terfenadine has resulted in sudden cardiac death)

Patient disease states: patients may have other conditions which would make it undesirable to administer that antibiotic (eg. giving erythromycin to patients with long QT syndrome has resulted in sudden cardiac death)

Other patient states: a pregnant patient should not receive antibiotics that may cause harm to the development of their unborn foetus/embryo.

Answer 2

Variable such as serum, body pH, ionic content, O2 level are not tested. Also you can not tell how the drug is metabolized and excreted or the side effects of the drug.