Antimicrobial Agents

Question 1

What is selective toxicity?

Answer 1

substance is toxic to the microbe and not the host

Question 2

bactericidal vs bacteriostatic antibiotic classes

Answer 2

bactericidal: cell wall synthesis, cell membrane, DNA replication, DNA-dependent RNA polymerase
bacteriostatic: folic acid metabolism, protein synthesis inhibitors

Question 3

bactericidal agent

Answer 3

kill agent; causes cell wall explosion; most dependent on peak concentration-dependent antibiotics; can be given in longer dosing intervals

Question 4

bacteriostatic agent

Answer 4

suppresses growth or cell division; might not be permanent; allows time for immune system to take over; maybe not a choice for immunocompromised pts; time-dependent (time above MIC is important)

Question 5

post-antibiotic effect

Answer 5

persistent suppression of microbial growth after antimicrobial agent has been cleared; **long with intracellular bacteriostatic agents; **short or no PAE with beta-lactams; helps bacteriostatic agents be more effective; **might make length of dosing interval versus the drug half-life less of a concern

Question 6

minimal bactericidal concentration (MBC)

Answer 6

?

Question 7

minimal inhibitory concentration (MIC)

Answer 7

applies more to bacteriostatic drug than bactericidal; **antibiotic in blood should exceed the MIC by 2-8X to offset tissue barriers to infection site

Question 8

What is resistance in terms of MIC?

Answer 8

if MIC is higher than the amt of drug you can safely give a pt, then the microbe is considered resistant to that drug

Question 9

**concentration-dependent antibiotics

Answer 9

effectiveness dependent on achieving peak concentration periodically in multiple dosing regimen; Peak/MIC or AUC/MIC; common for bactericidal agents that show conc-dependent toxicity

Question 10

**time-dependent antibiotics

Answer 10

effectiveness dependent on time (%) that concentration remains above MIC; Time/MIC; common for drugs whose slow killing requires maintained concentrations; **requires minimization of dosing interval relative to drug half-life or IV infusion

Question 11

narrow spectrum antibiotic

Answer 11

effective against either Gm+ or Gm- microbes; lower risk for superinfections

Question 12

extended spectrum antibiotic

Answer 12

affects a variety of Gm+ and Gm- bacteria

Question 13

broad spectrum antibiotic

Answer 13

affects both Gm+ and Gm- bacteria, +/- other microorganisms as well

Question 14

chemotherapeutic index

Answer 14

reflects the margin of safety expected when using an antimicrobial agent at its effective dose

Question 15

maximal efficacy

Answer 15

limit of the dose-response relation; *measures the clinical effectiveness of a drug

Question 16

**acquired microbial resistance

Answer 16

occurs as a result of antimicrobial therapy, esp. when a therapy has been used a lot in the environment; alterations in membrane or in transporters can mean drug fails to reach the target; maybe inactivated by efflux pumps

Question 17

how to avoid drug resistance

Answer 17

**administer antibiotics at doses sufficient to establish an effective concentration for a sufficient period of time (and throughout dosing interval for time-dependent drugs); terminate dosing when infection is resolved

Question 18

definitive antimicrobial therapy

Answer 18

identification of specific pathogen prior to treatment; determine the organism w/ drug sensitivity test and cultures of the infection

Question 19

empiric antimicrobial therapy

Answer 19

treatment w/out formal identification of specific pathogen; *often start this tx, take culture, switch to definitive; clears the infections faster

Question 20

mechanism of action of beta-lactam antibiotics

Answer 20

inhibit transpeptidases
activate autolytic enzymes in cell wall
bactericidal
time-dependent action

Question 21

Why are beta-lactam antibiotics most effective against dividing cells?

Answer 21

b/c organism starts to lyse its own cell wall to allow for division; not effective against organisms that already have a cell wall

Question 22

Why are beta-lactam antibiotics time-dependent?

Answer 22

they take a while to work; you have to wait for all of the cells to go through the division process

Question 23

other beta-lactamase general characteristics

Answer 23

wide distribution except in CNS
renal excretion, not metabolized
mainly gram+ aerobes

Question 24

resistance to beta-lactam antibiotics

Answer 24

*beta lactamases/penicillinases cleave these drugs & destroy their binding to the transpeptidases (PBPs) where they act

Question 25

adverse effects of beta-lactam antibiotics

Answer 25

cross-sensitization
delayed rxns like rashes
acute anaphylactic rxns
minimal toxicity

Question 26

What are the repository forms of PenG and what do they do?

Answer 26

procaine-PenG & benzathine-PenG for IM injections;
repository forms prolong the half-life; water-insoluble so dissolve slowly and have a slow release into the bloodstream so they are in circulation longer

Question 27

Why does Stevens-Johnson syndrome occur?

Answer 27

pts w/ renal insufficiency cannot clear the penicillin

Question 28

pharmacokinetics of aminopenicillins vs PenV

Answer 28

aminopenicillins have better bioavailability and half-life

Question 29

mechanism of action of beta-lactamase inhibitors

Answer 29

irreversibly inhibit the beta-lactamases to combat beta-lactamase activity in eliciting resistance to other beta-lactam antibiotics such as penicillins

Question 30

**What is the most widely prescribed class of antibiotic in the hospital setting?

Answer 30

cephalosporins

Question 31

general characteristics of cephalosporins

Answer 31

• -similar to penicillins (structure, inhibit cell wall synthesis, can cause allergy)
• -grouped into 4 generations based on spectra of activity
• -acid stable 1st generation
• -no topical application
• -disulfiram-like rxn w/ 2nd and 3rd gen, pseudomembranous colitis (CDAC) w/ 3rd and 4th gen

Question 32

early vs later generations of cephalosporins

Answer 32

early: better against gram+ (S aureus)
later: resistance to beta-lactamases, CNS penetration, more gram-, less gram+, anti-pseudomonal activity

Question 33

activity of carbapenems

Answer 33

bind to PBPs better than pens/cephs; penetrate outer membrane of gram- bacteria therefore **broadest activity of all beta-lactam drugs; resistant to most beta-lactamases but induce those that inactivate pens/cephs so antagonize their action; **active against extended-spectrum beta-lactamase producing organisms

Question 34

How does Daptomycin work?

Answer 34

pokes holes in bacterial cell membranes; forms complexes in presence of Ca that causes leakages of ions from bacteria; membrane depolarization