What are the 3 phenotypes of vancomycin resistance?
vanA, vanB, vanC
What group of organisms is vancomycin capable of killing? (name the class and the 5 major targets)
Gram-pos ONLY - *MRSA, *MSSA, *coag-negative staph, *PRSP, *c-dif (clostridium spp.) - Also targets other strep pneumoniae, viridians strep, group strep, enterococcus, corynebacterium, bacillus, listeria, actinomyces, clostridium spp., peptococcus, peptostreptococcus.
Since vanc is distributed widely in the tissues, you should use ________________ for dosing.
TBW (total body weight?)
How long does it take for vanc to distribute into the tissues?
1 hour - Peak should be drawn 1 hr post-infusion
For vancomycin, elimination T1/2 depends on _______ function.
Can pts who are allergic to PCNs be given vancomycin?
Yes! (different structure)
What's an e.g. of a target of vancomycin that is a multi-drug-resistant bacterium?
PCN-resistant streptococcus pneumoniae (PRSP)
Vanc treats ______-______ c-dif colitis.
Recall: what drug is used to treat mild-mod c-diff?
How does Red Man Syndrome occur? - Which drug is it a/w?
Infusion of vancomycin at too high a RATE - Also a/w other glycopeptides
In what specific type of infection would you prefer the 2nd gen glycopeptide dalbavancin to vancomycin? - Which genes must be present?
VRE (must have vanB or vanC gene, not vanA.)
What is the MoA of vancomycin?
Binds D-ala-D-ala to inhibit cell wall synthesis
What is the MoA of linezolid? (is resistance common or uncommon?)
Binds 50S ribosomal binding site (resistance rare)
What is the major class that linezolid can inhibit? List the main targets. - What is the other class?
Gram-pos: - *MSSA - *MRSA - *VRSA, - strep-pneumoniae (including *PRSP), - **enterococcus faecium and faecalis (including *VRE) Also: viridian streptococci, group streptococci, coag-neg staph, bacillis, listeria, clostridium spp (except c-diff), peptostreptococcus, c. acnes. Atypical bacteria: mycobacteria
What is unique about the pharmacology of linezolid?
What major category of pathogens is linezolid generally used for? What body area category is it NOT used for?
* Serious/complicated infections caused by resistant gram-positive bacteria: - Not used for UTIs
What is linezolid contraindicated with and what condition does it cause?
- SSRIs, MAOIs - Serotonin syndrome
What are the major side effects a/w linezolid?
* Thrombocytopenia/anemia - SSRIs/MAOIs: serotonin syndrome. - Lactic acidosis - BM suppression - Neuropathy
What category of drugs are linezolid and tedizolid?
What's the advantage of tedizolid over linezolid? Why isn't tedizolid prescribed more often?
- Doesn't cause serotonin syndrome - It's even more expensive than linezolid
What class of drugs does daptomycin belong in?
What class of bacteria is daptomycin active against? Name the bacteria. (*or at least the targeted ones).
Gram-pos: *MRSA *MSSA *VRSA coag-neg staph strep pneumoniae (including *PRSP) viridians streptococi group streptococci *Enterococcus faecium and farcalis (including *VRE)
*Daptomycin should NOT be used in the treatment of _____________.
*What is the major adverse effect a/w daptomycin?
Myopathy and CPK elevation (must continually monitor them)
Glycopeptides: mech of action (be specific)? - Time or conc-dependent? - Static or cidal?
Inhibits cell wall synth at a site different than beta-lactams, binding to D-alanyl-D-alanine portion of cell wall, preventing cross-linking. - Time-dependent - Bacteriocidal
Vancomycin: mech of resistance? - In what 2 organisms, specifically, is this an issue?
Resistant in VRE/VRSA due to change in D-alanyl-D-alanine binding site of PG.
Which glycopeptide is more potent than vanc?
How can linezolid be administered?
PO or IV
What class of drug is the quinupristin-dalfopristin combo? - MoA? - Static or cidal?
Synercid - Streptogramins - Protein synthesis inhibitor (50S ribosomal subunits; late stages) - Bacteriostatic, but syngeristic together to be bacteriocidal.
What organism class are quinupristin-dalfopristin effective against? - What is the main target organism? What others are its targets?
Gram-positives, namely VRE. Gram-positive organisms (developed for VRE) - Enterococcus faecium (including VRE)* - MSSA, MRSA - Coagulase-negative staphylococci* - PRSP*, and many more. Also coverage vs. gram-neg aerobes and atypical bacteria (in vitro).
How is quinupristin-dalfopristin cleared?
What are the glycopeptides we need to know?
VDTO - Vancomycin - Dalbavancin - Telavancin - Oritavancin
Name the 3 major side effects a/w vancomycin.
- Red man syndrome - Nephrotoxicity - Ototoxicity
Name the major side effects a/w dalbavancin.
GI s/s, skin rxns + flushing - Can also get red man syndrome
Name drugs that are highly active/focused towards vs. resistant gram-pos organisms.
Vancomycin Dalbavancin Telavancin Oritavancin Linezolid Tedizolid Daptomycin Quinupristin-dalfopristin
Quinupristin-dalfopristin: mech of resistance?
- Alterations in ribosomal binding sites (erm) - Enzymatic inactivation - Active transport out of the cell
Via what route is quinupristin-dalfopristin absorbed? - Does it penetrate CSF?
Parenterally - Minimally
How is quinupristin-dalfopristin eliminated?
Both via hepatic and biliary
What are the main clinical uses for Synercid (quinupristin-dalfopristin)? (2)
- VRE bacteremia - Complicated skin and soft tissue infections due to MSSA or Streptococcus pyogenes
Does quinupristin-dalfopristin affect CYP450?
P450 3A4 Inhibitor
Adverse effects of quinupristin-dalfopristin?
- Sever GI intolerance (N/V/D) - Venous irritation