L27 - O'Keefe - Intro to Antibiotics Part 2

Question 1

How does antibiotic selection differ for empiric vs directed/targeted therapy?

Answer 1

For directed therapy, since you know the organism and susceptibility, you can use a drug with a more narrow spectrum

*also, for directed therapy the antibiotic is given for a pre-defined duration

Question 2

Compare the duration of therapy for the 2 causes of meningitis…

Answer 2

Meningitis due to strep pneumoniae = treat for 10-14 days

meningitis due to Niesseria meningitidis = 7 days

Question 3

What are two types of therapies that can be employed for the use of antibiotics?

Answer 3

Prophylactic therapy and combination therapy

Question 4

Define prophylactic therapy

Answer 4

antibiotics are give to PREVENT the development of infection

choose therapy based on drug of choice for the most probably organism and susceptibility patterns of the region

administer as long as the patient is at risk

Question 5

Define Combination therapy (specifically…what are 3 things it can be used to do?)

Answer 5

1. broaden bacterial coverage to all organisms causing infection
2. decrease the emergence of resistance
3. take advantage of synergy by using more than 1 antibiotic

Question 6

What are two examples of prophylaxis (prevention) that were discussed in lecture?

Answer 6

peri-operative surgical prophylaxis

endocarditis prophylaxis

Question 7

Explain peri-operative surgical prophylaxis

Answer 7

wound infections can be caused by skin flora

during operations, antibiotics are given against skin flora to reduce wound infection

Question 8

explain endocarditis prophylaxis

Answer 8

to prevent endocarditis, antibiotic is given against oral flora for dental procedures

applies if person has a damaged or prosthetic heart valve or previous endocarditis

Question 9

For both prophylaxis examples, what is the overall dosing regimen?

Answer 9

single dose given only

no benefit from prolonged antibiotic use

Question 10

What are the 3 possible effects from combination therapy?

Answer 10

synergy
additive
antagonism

Question 11

Define synergy

Answer 11

the antimicrobial effect of the two drugs together is greater than the additive activity of each one separately

(A + B) > A + B

Question 12

Define additive

Answer 12

the antimicrobial activity of the drugs used together is equal to the sum of each one separately

(A + B) = A + B

Question 13

Define antagonism

Answer 13

the antimicrobial activity of the drug combo is less than what you would expect from the addition of each one

(A + B)

Question 14

Give an example of synergy

Answer 14

For enterococcal endocarditis:

penicillins don’t kill enterococcus, but if you add gentomyacin (aminoglycoside) you get rapid killing

Question 15

Compare and contrast bacteriostatic vs bactericidal (definitions)

Answer 15

Bacteriostatic = antibiotic INHIBITS bacterial growth, killing depends on host defense mechanisms (to “cure” the infection)

Bactericidal = antibiotic KILLS bacteria, is less dependent on host defense mechanisms

*note: he said to know whether classes are bacteriostatic or bactericidal

Question 16

What are disadvantages of bacteriostatic antibiotics?

Answer 16

If host defenses are inadequate, organisms that were only partially inhibited could survive/replicate and give a recurrent infection upon stopping use of the antibiotic (or if serum conc of the antibiotic go below the MIC)

Question 17

Give an example where host defenses won’t be sufficient to get ride of infection

Answer 17

Endocarditis = infection on a clot in a valve

because there’s no blood supply to the clot, host defenses don’t reach it

Question 18

What are examples of bacteriostatic antibiotics?

Answer 18

macrolides, ketolides, tetracyclines, glycylcylines, sulfonamides, clindamycin, Synercid, and linezolid

*note: he said to know whether classes are bacteriostatic or bactericidal

Question 19

When would you want to use a bactericidal antibiotic (overall)?

Answer 19

it’s preferable if the host immune system is compromised or doesn’t function well (ex: neutropenia or immunosuppresion)

*remember: neutropenia = low neutrophil levels

Question 20

Bactericidals are required for the treatment of…? (give 4 examples)

Answer 20

meningitis (host defenses aren’t effective in sub-arachnoid space)
endocarditis
osteomyelitis
febrile neutropenia

Question 21

What are examples of bactericidal antibiotics?

Answer 21

penicillins, cephalosporins, carbanpenems, aztreonam, fluoroquinolones, aminoglycosides, vancomycin, daptomycin, Bactrim, and metronidazole

*note: he said to know whether classes are bacteriostatic or bactericidal

Question 22

What is plotted for a pk graph? pd graph? pk/pd graph?

Answer 22

PK graph = conc vs time
PD graph = conc vs effect (aka dose response curve)
PK/PD graph = effect vs time

Question 23

What are two important PD parameters for antibiotics?

Answer 23

AUC/MIC

Time above MIC

Question 24

What is PAE?

Answer 24

Post-antibiotic effect

it’s the time it takes for the bacteria to re-grow once serum conc of antibiotic fall BELOW the MIC (is drug and organism specific!)

ex: sometimes the organism starts to grow immediately but sometimes there’s a gap (the gap is the PAE)

Question 25

What is the benefit of a long PAE?

Answer 25

You can safely spread the dose out and allow serum concentrations to fall below MIC

Question 26

Describe the PAE for gram positive bacteria

Answer 26

all antibiotics have some PAE | beta-lactams have a PAE of 2 hours

Question 27

Describe the PAE for gram negative bacteria

Answer 27

prolonged PAEs seen with: protein or nucleic acid synthesis inhibitors (ex: aminoglycosides or fluoroquinolones)

Question 28

Define concentration dependent killing

Answer 28

Get more rapid and extensive killing with higher serum concentrations...the higher the level of drug in serum, the more rapid the killing Prolonged persistent effects (post-antibiotic)

Question 29

Give an example of concentration dependent killing

Answer 29

Once daily aminoglycosides | give a high "once a day" dose and avoid toxicity

Question 30

Define time dependent killing

Answer 30

killing depends on time of exposure above MIC (not higher serum concentrations) seen with highly resistant organisms

Question 31

How would dosing differ for time dependent killing?

Answer 31

can extend dosing (ex: infuse for 4 hours instead of 1) so the drug stays in the patient for a longer period of time even if the peak level is lower *you're increasing exposure of patient to a concentration of drug that's effective against the organism

Question 32

what is the general approach to the selection of an antimicrobial? (give 5 "steps")

Answer 32

1. confirm presence of infection 2. select empiric therapy (start therapy before you know what the organism is) 3. identify the pathogen 4. modify/streamline the antibiotic therapy 5. monitor therapeutic response

Question 33

What are the 3 infection-specific parameters to consider when choosing an antibiotic?

Answer 33

1. severity of infection 2. site of infection 3. infecting organism (ex: don't give orally for sepsis)

Question 34

What are 6 host-specific factors to consider when choosing an antibiotic and why?

Answer 34

1. allergies (and degree of cross-reactivity) 2. age (elderly have dec renal function and thus maintain antibiotics for longer) 3. pregnancy or nursing (potential effect on fetus and there's also increased in Vd as well as renal clearance) 4. rental and hepatic function 5. concomitant drug therapy 6. underlying disease states

Question 35

Why is renal/hepatic function important for choosing antibiotics?

Answer 35

Diminished function may lead to drug accumulation and undue toxicity so you have to adjust doses

Question 36

What antibiotics are primarily eliminated by the kidneys? (7)

Answer 36

``` most beta-lactams vancomycin aminoglycosides some fluoroquinolones Bactrim daptomycin tetracycline ```

Question 37

What antibiotics are primarily eliminated/metabolized by the liver? (9)

Answer 37

``` macrolides Synercid linezolid clindamycin metronidazole some fluoroquinolones Bactrim doxycyline tigecycline ```

Question 38

What is one example where you must consider concomitant drug therapy when choosing an antibiotic?

Answer 38

azoles for fungal infections inhibit the cyp system ex: in the case of a kidney transplant, cyclosporins are given and azole would increase the levels of cyclosporins

Question 39

what disease states may predispose patients to infection/pathogens?

Answer 39

diabetes and soft tissue infections burns and skin infections trauma patients

Question 40

What are the 7 drug factors you must consider when choosing an antibiotic?

Answer 40

1. in-vitro activity and current susceptibilities 2. established clinical efficacy 3. drug of choice charts 4. PK and tissue penetration (MUST get sufficient concentrations at the site of infection) 5. PD (type of bacterial activity needed for organism and infection type) 6. side effect profiles 7. cost

Question 41

Which is more costly...IV or oral antibiotics?

Answer 41

IV

Question 42

Monitoring serum concentrations and toxicity can be costly. This is done for which group of antibiotics?

Answer 42

Aminoglycosides