Antimicrobials Flashcards
Define Minimum Inhibitory Concentration (MIC)
lowest concentration of an antimicrobial agent that prevents visible growth in agar or broth dilution susceptibility test
Define breakpoint
- MIC or zone diameter value used to indicate susceptible (S), intermediate (I), and resistant (R)
- some labs report NI (not interpreted) if no established breakpoint
Define the efficacy ratio
- divide resistant breakpoint MIC by the MIC obtained by broth dilution
- tool to evaluate relative efficacy of different antimicrobial drugs
Which antimicrobials are considered broad spectrum?
- tetracyclines
- phenicols
- quinolones
- 3rd- and 4th-generation cephalosporins
What antimicrobials are considered narrow spectrum?
- Glycopeptides & bacitracin (G+)
- Polymixins (G-)
- Aminoglycosides & sulfonamides (aerobes)
- Nitroimidazoles (anaerobes)
What is the MOA of beta-lactams?
- target and bind to penicillin-binding proteins (PBPs), inhibiting bacterial cell wall synthesis
What is the bacterial mechanism of resistance to beta-lactams?
- enzymatic destruction of beta-lactam rings
- target PBP modification
- reduced intracellular accumulation
What is the MOA of glycopeptides?
inhibit the last stages of cell wall assembly by preventing cross-linking reactions
What is the bacterial mechanism of resistance to glycopeptides?
- target modification
- production of false targets
What is the MOA of quinolones?
targets DNA gyrase and topoisomerase IV of the bacteria and inhibits the necessary step of supercoiling
What is the bacterial mechanism of resistance to quinolones?
- target modification
- reduced intracellular accumulation
What is the MOA of aminoglycosides?
target and bind to the 30s ribosomal subunit to cause misreading of the genetic code which results in inhibition of protein synthesis
What is the bacterial mechanism of resistance to aminoglycosides?
- antibiotic (structural) modification
- target modification
- reduced uptake
What is the MOA of macrolides?
target and bind to 50S ribosomal subunit to inhibit translocation and transpeptidation process, resulting in inhibition of protein synthesis
What is the bacterial mechanism of resistance to macrolides?
- reduced intracellular uptake
- target modification
What is the MOA of tetracyclines?
target and bind to 30S ribosomal subunit to prevent aminoacyl-tRNA to attach to RNA-ribosome complex, inhibiting protein synthesis
What is the bacterial mechanism of resistance to tetracyclines?
- reduced intracellular accumulation
- target modification
What is the MOA of rifampin?
interacts with the beta-subunit of the bacterial RNA polymerase to block RNA synthesis
What is the bacterial mechanism of resistance to rifampin?
- target modification
What is the MOA of sulfonamides?
targets dyhydropteroate synthase (DHPS) and prevents addition of para-aminobenzoic acid (PABA), inhibiting folic acid synthesis
What is the bacterial mechanism of resistance to sulfonamides?
- target modification
What are some examples of narrow-spectrum aminoglycosides?
- streptomycin and dihydrostreptomycin
- active against aerobic gram neg
What are some expanded spectrum aminoglycosides?
- neomycin, kanamycin
- active against several gram pos and many gram neg aerobes
- gentamicin, amikacin
- extended spectra that includes Pseudomona aeruginosa
What are aminoglycosides used for?
- control local and systemic infections caused by aerobic bacteria (generally gram neg)
- e.g. septicemia; tracheobronchitis, pneumonia, osteoarthritis, infections of urinary tract
- potential for nephrotoxicity so contraindicated if plasma creatinine (>5 mg/dL)