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PHARMACOLOGY 3 > 5 – Principles of Antimicrobial Therapy > Flashcards

5 – Principles of Antimicrobial Therapy Flashcards

1
Q

What is an antibiotic?

A
  • Substance produced by bacteria and active against other bacteria
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2
Q

What is an antimicrobial?

A
  • Substance (either naturally produced or synthetic) that is active against microbes
    o Bacteria
    o Fungi
    o Protozoa
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3
Q

How is it possible that there is salmonella in ‘free from’ chicken with resistance? (even when never treated with it)

A
  • INTRINSIC RESISTANCE
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4
Q

What do you consider when choosing an antimicrobial therapy? (questions you will ask)

A
  • Where is the infection located?
  • Will the antimicrobial distribute to the infection site?
  • Will the antimicrobial be effective in the pathogen’s environment
  • What is the appropriate drug formulation and dosage regimen?
  • What is the most appropriate DURATION of therapy?
  • What adverse drug reactions or toxicities may occur?
  • For food animals, can you stay ‘on label’?
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5
Q

Where is the infection located?

A
  • If in urine=easier
  • If have a ‘barrier’=harder to get microbials there
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6
Q

Will the antimicrobial be effective in pathogen’s environment? Ex. abscess

A
  • Rifampin, florfenicol and tetracycline work well
  • *pH is different in abscesses
  • Various that are not effective
  • *superficial: usually don’t treat with antimicrobials (usually open it and clean it)
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7
Q

What antimicrobials are INEFFECTIVE in abscess? (ex. in horses)

A
  • Aminoglycosides
  • Beta-lactams
  • Trimethoprim/sulpha
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8
Q

What is appropriate drug formulation and dosage regimen?

A
  • Ideal to have the drug concentrated
  • Avoid GI being exposed to them
  • Ex. IV regional infusion (occlude vein and will leak out)
  • Ex. interosseous infusion (into medullary cavity of the bone)
  • Ex. ‘beads’ with surgeries
  • *none are foul proof
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9
Q

What is the most appropriate DURATION of therapy?

A
  • Ex. Convenia lasts in body for a LONG time
  • Less control
  • Especially if drugs lasts multiple weeks but infection is cleared in a few days
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10
Q

What does successful antimicrobial therapy require? (2 thoughts)

A
  • Administering sufficient dose so that bacteria at site of injection are KILLED?
  • Sufficiently SUPPRESSED so that they can be eliminated by host’s immune system?
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11
Q

High plasma drug concentrations are ASSUMED to be advantageous

A
  • Large concentration of drug to DIFFUSE from plasma into various tissues and body fluids
  • Soft tissue infections: most bacteria are located in ECF
    o So concentration in plasma will resemble amount in the ECF (equilibrium between them)
  • *exception: new macrolide drugs have very low plasma concentrations, but extremely high tissue concentrations
    o Bind to leukocytes and are carried to site of infection (ex. lungs)
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12
Q

Minimum inhibitory concentration (MIC)

A
  • Lowest drug concentration that INHIBITS bacterial growth
  • Dose to reach target plasma concentration of 2-10x the MIC
    o Depends on the drug
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13
Q

Minimum bactericidal concentration (MBC)

A
  • Lowest drug concentration to KILL 99.9% of the bacteria
  • Often can’t reach it as the concentration is so high
    o May reach toxic levels
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14
Q

Mutant prevention concentration (MPC)

A
  • MIC of the LEAST-susceptible (ex. more resistant) single-step mutant bacterial population
  • Hard to reach or unsafe (SUPER HIGH!)
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15
Q

What happens if local drug concentration is less than MIC? (susceptibility testing)

A
  • No effect
  • *Resistant
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16
Q

What happens if local drug concentration equals MIC? (susceptibility testing)

A
  • Doubtful effect
  • *intermediate
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17
Q

What happens if local drug concentration is more than MIC? (susceptibility testing)

A
  • Effective
  • *susceptible
18
Q

What are S, I and R based on?

A
  • Achievable PLASMA levels
  • But concentration at site of infection, may be very different
  • *works well for things like septicemia or wounds
19
Q

MIC determination using microdilution

A
  • Low drug concentration=lots of growth
  • MIC is when there is NO more growth
  • Ex. can get no growth but then growth reappears
20
Q

Agar disk diffusion

A
  • Measure zones of inhibition
  • Qualitative, NOT quantitative
21
Q

E-test

A
  • Strip with antimicrobial gradient
  • Expensive
  • MIC like results
22
Q

MIC of bacterial populations

A
  • MIC50 or MIC90
  • It can help and give you an idea of how susceptible it is, but does not guarantee efficacy
23
Q

What are some key points for antimicrobial susceptibility testing with Culture & Susceptibility (C&S) panel?

A
  • Guides your decision by providing, which pathogen and susceptibility of them
  • Does NOT guarantee drug success or failure
  • Wont have C&S result immediately
    o Need to select initial therapy empirically
    o Why its worth remembering likely pathogen and susceptibility
24
Q

What does susceptibility testing NOT account?

A
  • Host immune system
  • Drug distribution in body
  • Drug efficacy in plasma/tissue vs. broth/agar
  • Bacterial growth rate and inoculum size
  • Mixed infections
  • Infection environment
  • In vivo antimicrobial
25
Q

When assessing antimicrobial efficacy what do you want to compare?

A
  • Those with therapy to those without therapy
  • *animals will also get better on their own, compare the 2 percentages!
26
Q

Genomics for susceptibility testing

A
  • ID key genetic determinants of resistance (eg. mecA, ampC genes)
  • *future diagnostic approach for fast, accurate and cheap antimicrobial susceptibility testing
  • **end goal: that clinics will be able to test genes and then treat
    o Just because it has the gene, does not mean it will be resistant, but it likely will be
27
Q

What are the antimicrobial categories?

A
    1. Bactericidal
    1. Bacteriostatic
  • **not absolute, do NOT choose therapy based on them
    o NOT that relevant
28
Q

Bactericidal antimicrobials

A
  • Ratio of MBC to MIC is <4-6
  • Ex. possible to obtain concentrations in the patient that will kill 99.9% of bacteria
29
Q

Bacteriostatic antimicrobials

A
  • Ratio of MBC to MIC is large
  • Ex. its not safe or feasible to administer enough antimicrobial to kill 99.9% of bacteria
30
Q

What is the Post-Antibiotic Effect (PAE)

A
  • Bacterial growth remains suppressed after the [antimicrobial] has dropped below MIC (‘no drug’)
  • may be reason that many dosage regimens are effective, despite not maintaining concentrations >MIC
    o *may allow for LONGER INTERVAL BETWEEN DOSES (convenience, $, AE)
  • *dependent on specific combo of antimicrobial and bacteria
31
Q

PAE and fluroquinolones

A
  • Long with gram positives and gram negatives
32
Q

What are important drugs with short PAE?

A
  • Penicillins
  • Cephalosporins
  • Trimethoprim/sulphas
  • *likely need to dose them for longer
33
Q

When looking at bacterial kill-curve studies, they show 2 ‘categories’ of antimicrobials, what are they?

A
  1. Concentration dependent
  2. Time dependent
34
Q

Concentration dependent antimicrobials

A
  • More drug you have and more exposure you have relative to MIC=better it will be
    a. AUC : MIC want it at least 10x
    b. Cmax : MIC want it 125x
35
Q

How do you know if a antimicrobial is concentration dependent?

A
  • As concentration of drug goes up=getter stepper=killing more
36
Q

Time dependent antimicrobials

A
  • Time above MIC is important!
    o Doesn’t matter if 2x, 5x, or 10x over MIC
  • *important concentrations do NOT drop quickly or too much over time
  • When does the tissue or plasma concentration ‘hit’ the MIC?
  • *want at least 50% of dosing interval want concentration to be above MIC
  • *dosing more often is better (x2 a day is likely fine, but going to 4x not necessary)
    o May be poor client compliance
37
Q

If doing infrequent dosing, what can be used to prolong exposure?

A
  • ‘long-acting form’
    o Slow absorbing (‘flip-flop’) formulations (ex. long-acting OTC)
    o High protein binding (cefovecin)
  • *sometimes concentrations reached are NOT high enough=not sufficient
38
Q

Problems interpreting time over MIC: oral vs IV

A
  • IV: increase and then decrease, lots of time not above MIC
  • Oral: above MIC for first bit and then lower
  • *both have same time above MIC, but way they get there is different
  • *neither is ideal, but either could be effective
39
Q

How do you know if an antimicrobial is time dependent?

A
  • When you increase dose but there is not benefit past a point
  • *longer you have concentrations above MIC=max efficacy
40
Q

Why is getting the dose right so important?

A
  • *Important to know HOW TO DOSE
41
Q

How are vet antimicrobials categorized?

A
  • *based on importance in HUMAN HEALTH
    1. Very high: limited or no alternatives
      o *can be appropriate to use in some cases, but need to UNDERSTAND WHY
    1. High: not limited
    1. Medium: not used in human med, but maybe limited alternatives
    1. Low: not used in human med at all (ex. ionophores)

PHARMACOLOGY 3 (15 decks)

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