Antimicrobial Agents Flashcards
What is selective toxicity?
substance is toxic to the microbe and not the host
bactericidal vs bacteriostatic antibiotic classes
bactericidal: cell wall synthesis, cell membrane, DNA replication, DNA-dependent RNA polymerase
bacteriostatic: folic acid metabolism, protein synthesis inhibitors
bactericidal agent
kill agent; causes cell wall explosion; most dependent on peak concentration-dependent antibiotics; can be given in longer dosing intervals
bacteriostatic agent
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)
post-antibiotic effect
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
minimal bactericidal concentration (MBC)
?
minimal inhibitory concentration (MIC)
applies more to bacteriostatic drug than bactericidal; **antibiotic in blood should exceed the MIC by 2-8X to offset tissue barriers to infection site
What is resistance in terms of MIC?
if MIC is higher than the amt of drug you can safely give a pt, then the microbe is considered resistant to that drug
**concentration-dependent antibiotics
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
**time-dependent antibiotics
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
narrow spectrum antibiotic
effective against either Gm+ or Gm- microbes; lower risk for superinfections
extended spectrum antibiotic
affects a variety of Gm+ and Gm- bacteria
broad spectrum antibiotic
affects both Gm+ and Gm- bacteria, +/- other microorganisms as well
chemotherapeutic index
reflects the margin of safety expected when using an antimicrobial agent at its effective dose
maximal efficacy
limit of the dose-response relation; *measures the clinical effectiveness of a drug
**acquired microbial resistance
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
how to avoid drug resistance
**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
definitive antimicrobial therapy
identification of specific pathogen prior to treatment; determine the organism w/ drug sensitivity test and cultures of the infection
empiric antimicrobial therapy
treatment w/out formal identification of specific pathogen; *often start this tx, take culture, switch to definitive; clears the infections faster
mechanism of action of beta-lactam antibiotics
inhibit transpeptidases
activate autolytic enzymes in cell wall
bactericidal
time-dependent action
Why are beta-lactam antibiotics most effective against dividing cells?
b/c organism starts to lyse its own cell wall to allow for division; not effective against organisms that already have a cell wall
Why are beta-lactam antibiotics time-dependent?
they take a while to work; you have to wait for all of the cells to go through the division process
other beta-lactamase general characteristics
wide distribution except in CNS
renal excretion, not metabolized
mainly gram+ aerobes
resistance to beta-lactam antibiotics
*beta lactamases/penicillinases cleave these drugs & destroy their binding to the transpeptidases (PBPs) where they act
