Clinical use of antibiotics

Question 1

Describe the principles that determine empirical antibiotic use.

Answer 1

1) What is the infectious syndrome (site of infection) that I will be treating?
2) What are the common pathogens that might be causing the syndrome?
3) What is the likely antibiotic resistance of the organisms being considered?
4) what is the most appropriate antibiotic to use?

Question 2

Describe the difference between bactericidal and bacteriostatic antibiotics and how they are defined based on MIC and MBC levels.

Answer 2

A bacteriostatic antibiotic is one that stops bacteria from reproducing, while a bactericidal antibiotic is one that kills bacteria.

MIC is the lowest concentration of an antimicrobial that will inhibit visible growth of a microorganism following incubation.

MBC is the minimal concentration of antibiotic that will kill 99.9% of organisms.

GENERALLY:
A bactericidal antibiotic has MBC/MIC 4

Question 3

Understand the different methodologies used to determine MIC and MBC

Answer 3

MIC:
1) Tube dilution (broth dilution) susceptibility testing–> serial dilutions of an antibiotic are made in a liqued medium, inoculated with a standardized number of organisms and incubated from a prescribed time. Tubes are examed for evidence of bacterial growth (cloudy or turbid appearance).

2) Disk diffusion (Kirby-Bauer): suspension of isolate at a specified concentration is pepared and then spread evenly onto a large agar plate. Disked are impregnated with defined concentrations of different antiobiotics, after incubation, the diameter of a clear circular zone of no growth in the immediate vicinity of disk is measured, diameter correlates to MIC.
3) E test- variation of kirby-bauer, uses strip with gradations of different concentrations of antiobiotic in an agar plate spread with suspension of the isolate. After incubation and growth, ellipse of no growth occurs, Strip determines where MIC is.

MBC- sample from each of the clear tubes (i.e., the ones lacking growth) is removed and plated on growth medium lacking antimicrobial. Growth on plates indicates that viable cells were present in the tube. The concetration of antibiotic that killed 99.9% of the organisms in the initial inoculum is the MBC.

Question 4

Describe the principles involved in setting antimicrobial breakpoints.

Answer 4

• Cp of antimicribial should be >MIC
• Pharmacokinetics/pharmacodynamics of antimicrobial
• Pattern of susceptibility
• Clinical experience

Question 5

Describe the potential pitfalls in setting AND interpreting antimicrobial breakpoints.

Answer 5

Breakpoints are not adjusted for:

• site of infections
• Number of organisms in an infection
• condtions of the host (i.e. pH)
• host’s defenses

Breakpoints change over time b/c of clinical data.

Question 6

Describe the relationship between maximal serum concentration (Cp) and MIC in order for a bacterium to be potentially considered “susceptible” to a given drug.

Answer 6

Cp must be >MIC for a bacterium to be considered suscpetible to a given drug.