Lecture 16: Antibiotics 1

Question 1

What are the factors that influence infection?

Answer 1

Virulence of bacteria

Number of bacteria

Host resistance (systemic and local)

Question 2

What are the local host resistance mechanisms to infection?

Answer 2

Cleaning

Closure

Contraction

Question 3

Considerations when selecting antibiotics

Answer 3

Identification of the organism (antibiotic targeted to specific organism is better)

Susceptibility of organism to a particular agent

Site of infection (CNS, brain, bone, prostate are sites of limited penetration)

Drug characteristics (lipid solubility, molecular weight, protein binding)

Pharmacodynamics (drug concentration vs effects)

Pharmacokinetics (drug absorption, distribution, elimination)

Route of administration

Patient factors

Safety (adverse effects, allergies)

Cost

Question 4

Why is it important to identify the organism while selecting antibiotics

Answer 4

Helps preserve the normal microflora of the person

Question 5

Why are different routes of administration chosen?

Answer 5

Oral route (for infections that are mild and can be treated on outpatient basis)

Intravenous (most serious infections)

Intramuscular (acts rapidly)

Topical (infections on to the skin surface)

Question 6

Patient factors in selecting antimicrobial agents

Answer 6

Immune system (weakened?)

Renal function (most antibiotics are cleared through kidneys)

Hepatic function

Poor perfusion

Age (young and elderly are at higher risk of infection)

Pregnancy/lactation

Question 7

What is empiric therapy

Answer 7

Different from directed therapy

Empiric therapy is when we select therapy based on our best guess, which is based on knowledge of the patient’s symptoms

We don’t wait for all the diagnostic tests to come back

Question 8

Why would we choose empiric therapy instead of directed therapy?

Answer 8

Site of infection

If the person is immunocompromised (might die before we get tests back)

Neutropenia (low neutrophils)

Hospital acquired infection (we might know what infections are circulating, which will help select antibiotics)

Age (very young and very old respond best to empiric)

Question 9

What are the three ways to use antimicrobials?

Answer 9

Prophylaxis (surgery)

Therapy

Suppression

Question 10

Define bactericidal

Answer 10

Kill bacteria at concentrations achievable in the patient

Needs to be at least 3log10 kills to be considered bactericidal

See figure

Question 11

Define bacteriostatic

Answer 11

Arrest the growth and replication of organisms, limiting the spread of infection

See figure

Question 12

What are the two types of dosing strategies?

Answer 12

Concentration dependent killing

Time-dependent killing (concentration independent)

Question 13

What is concentration dependent killing?

Answer 13

A significant increase in the rate of bacterial killing with higher concentrations of the drug

Useful property for rapid killing of infective pathogens

See figure

Question 14

What is time-dependent killing?

Answer 14

Require time to achieve effective killing

Increase in time will result in more bacteria dying

Higher concentrations of the drug do not increase the rate of bacterial killing

See figure

Question 15

Different spectrums of antimicrobial activity

Answer 15

Narrow

Extended

Broad

Question 16

Narrow spectrum antimicrobial agents

Answer 16

Act on a limited group of microorganisms

example: isoniazid

Question 17

Extended spectrum antimircobial agents

Answer 17

Effective against one class of organisms as well as a significant number in a different class

ex: ampicillin

Question 18

Broad spectrum antimicrobials

Answer 18

Kill a range of antimicrobial species

Question 19

When are combinations of antimicrobials used?

Answer 19

Unkown organism

Polymicrobial infection (need to increase spectrum of treatment)

Antibiotic synergy (one antibiotic can increase effectiveness of another)

Patient/population factors

Question 20

Why are combinations of antimicrobials used?

Answer 20

What is known in the hospital

Dose related toxicity

Question 21

Disadvantages of antimicrobial combinations

Answer 21

Superinfection

Eradication of normal microflora

Resistance (MDR organisms)

Adverse effects (greater toxicity)

Patient adherence to therapy

Increased cost

Question 22

What is synergism

Answer 22

When the effect of two drugs in combination is greater than the sum of the effect when two drugs are administered independently

Question 23

What is antagonism

Answer 23

When the effect of two drugs in combination is less than the sum of the effect when the two drugs are used independently

Question 24

How is antibiotic synergy tested?

Answer 24

Checkerboard method in 96 well plate

Question 25

What are the different mechanisms of synergy?

Answer 25

One drug enhances uptake of the second

One drug enhances the metabolic effect of the other

Drugs act sequentially in a common pathway

Drugs inhibit the same target but in different ways

Two or more drugs inhibit targets in different pathways

Question 26

What are the different mechanisms of antagonism?

Answer 26

Not very well studied because it is disadvantageous for clinical therapy