Dr. Cluck Clinical Application Gram(+) Flashcards
What is required for every patient on VNC?
Therapeutic Drug Monitoring
AUC or through-based monitoring
What are other nephrotoxic agents interacting with VNC?
Aminoglycosides
Pip-Tazo
Adverse effects of VNC
-possible Nephrotoxicity/Ototoxicity
-VNC Infusion Reaction (painful)
What is the VNC Infusion Reaction?
-Histamin-related reaction (rash)
-IV administered too quickly
-Normal infusion rate 1g/hr
What is the disadvantage of the VNC + Pip-Tazo combination?
-Synergistic Nephrotoxicity (both are nephrotoxic)
still a common combo
Pip-Tazo: for gram (-) coverage (also Pseudo and anaerobes)
VNC: mainly for MRSA, Gram (+) coverage
Which drug is appropriate to substitute with Pip-Tazo?
-Cefepime(4) for Gram(-) also: Pseudomonas, Gr(+), MSSA
-but no anaerobes coverage (anaerobes are often bystanders)
Spectrum of Activity for VNC
EXAM!!!
-Only Gram (+)
-MRSA
-Streptococcus (not to best option, there are better drugs -> ß-lactams work well)
-Enterococci
Why is VNC not the best choice for Streptococcus?
-ß-lactams cover Streptococcus well
-It damages the kidneys
How would C. diff be treated with VNC?
-PO (bc the absorption is weak and it works in the gut where C. Diff is present)
-IV has no activity
Drug Class of Zyvox
Linezolid
-Gram (+) coverage
-MRSA
-Streptococcus (fine for superficial, skin tissue)
-VRE
-Hepatic eliminated (metabolites can accumulate)
Why are Linezolids used for superficial infections rather than invasive (Bacterimia, CNS) infections?
It is bacteriostatic
MOA of Linezolids?
Binds to 50S and block 50S + 30S (70S) formation
Drug formulations of Zyvox
-IV and PO (2x daily)
-100% IV to PO conversion
Adverse effects of Linezolid
!!!
-Myelosuppression (bone marrow) after 14 days of use (dip in platelets)
-lactic acidosis, teeth coloring (not seen by Dr. Cluck)
-optic neuritis
-weak MOA inhibitor
! -interacts with SSRI and other drugs with serotonergic activity
Cubicin
!!!
-Daptomycin
-IV Only
-Gram (+), MRSA, Strepto, VRE - same as VNC
-cannot treat pneumonia (inactivated by pulmonary surfactant) !!!
-drug interaction with statins !!!
Adverse effects of Daptomycin
!!!
-Eosinophilic pneumonia (hypersensitivity)
-if used with statins: Myopathy
-> Monitor weekly CPK (creatine phosphate kinase) !!
3 big drugs for invasive Gram (+) infections
-VNC (DOC for MRSA)
-Linezolid (also MRSA)
-Daptomycin (also MRSA)
What is VISA?
-Subpopulation that can not be treated with VNC
-treat with Daptomycin, Linezolid, or Ceftaroline(5)
-VNC intermediate Staph aureus (more often than VRSA)
(VRSA - VNC resistant Staph aureus)
-cell wall starts to thicken, tolerance to VNC
When is Linezold preferred over VNC (Gold-standard)?
-MRSA-Pneumonia
-bc VNC is weight-based dosing - it doesn’t fit all
-clinical trial: it took 9 days to reach therapeutic level vs. linezolid is therapeutic right away
Cleocin
-Clindamycin (MOA like erythromycin)
-IV, PO, supp., topical
-probably 1:1 IV-PO conversion, but the GI doesn’t tolerate high doses
-lincosamide antibiotic
-share MOA and MOR with macrolides
Spectrum of activity
!!!
-Excellent anaerobic
-mouth and respiratory tract (except CNS)
-good Gram (+) except Entercocci
-Clinically used for MRSA (Peds) !!
-cause C. Diff !!
Thumb of Rule for Action site of Clindamycin
above the diaphragm use Clindamycin
below the diaphragm use metronidazole
kind of TRUE
Rifadin (Rifampin)
-Rifamycin derivative
-IV and PO, 1:1 conversion, but high doses are not well tolerated, so given in 2 doses
-check for DDI: CYP induction !!
-red dye of fluids !! (like metronidazole) !!
Don’t use it as MONOTHERAPY: adjunct ONLY: bc resistance develops quickly !!
Why should Rifampin be used with caution?
-check for DDI: CYP induction: drugs are getting way more effectively cleared by CYP enzymes (there are more enzymes, channels, and transporters affected) !!!
Why does Rifampin work against infections on prosthetic devices?
Because it also works when the bacteria slows replication down (which they do in biofilms)
Dalbavancin
IV ONLY
-semisynthetic glycopeptide (lipoglycopeptide)
-interferes with peptidoglycan cross-linking in the cell wall by binding to D-Ala-D-Ala of stem peptides, like VNC
-lacks the secondary mechanism seen in other lipoglycopeptides
-require renal adjustment in severe impairment OR don’t adjust and give lower dose
Adverse effects: GI irritation and headache
-no drug interactions
At what points does Dalbavancin outperform VNC?
-Longer half-life
-1 dose of Dalbavancin = 14 days of VNC
What does Dalbavancin and Oritavancin have in common?
EXAM !!!
-Both are only FDA-approved for skin soft tissues
-so anything else than skin soft tissue infection, a single dose would NOT be sufficient !!!
would need more than one dose (grey area)
Difference between Dalbavancin and Oritavancin?
!!!
Oritavancin covers VRE and Enterococci; Dalbavancin does not!!
Spectrum of Activity Dalbavancin
-only Gram (+)
-NO activity against VREnterococci carrying vanAgene(1-3)
-no drug interactions
Oritavancin
-Orbactiv/Kimyrsa
-Lipoglycopeptide
-in phase 3 for soft skin tissue infection (ABSSSI)
-covers VRE (unlike Dalbavancin)
-MOA is different
-IV only
Difference between the trade names of Oritavancin
Orbactiv (3hr infusion in dextrose solution)
Kimyrsa -> changed formulation: shorter infusion (1hr) stable in saline, but more expensive
What is the MOA for
- Inhibition of Transpeptidation
- Inhibition of Transglycolysation
- Disruption of the cell wall
When to use Oritavanvin?
-Skin soft tissue infection
-avoid a PICK line infusion
Telavancin (Vibativ)
A mix of Daptomycin and VNC
-VNC derivative (10x activity)
-similar to Oritavancin in regards to antimicrobial profile
-daily administration needed
-IV only
Adverse effects of Telavancin
-increased serum creatinine
-prolonged QT interval
Analogy “Vancins” and DAPTOMYCIN-VNC MIX
-“Vancins” are lipopeptide
-Daptomycin (cyclic lipopeptide) and VNC (Glycopeptide)
Why might Telavancin be inconvenient for patients?
Requires daily dosing
What is the intended use of Telavancin?
-FDA approved for MRSA HAP/VAP (hospital and ventilator-acquired pneumonia + cSSSSI (complicated skin and skin structure infection)
-included in guidelines for complicated MRSA bacteremia/endocarditis (C-III)
Tedizolid (Sivextro)
-congener of linezolid (same category), similar MOA
-marketed as the better version of Linezolid (but it wasn’t)
-> once daily instead of twice daily, no Myelosuppression (but possibly due to lower dosing), no SSRI interaction
-but very expensive
-IV and PO
-active against Gram (+) aerobic and anaerobes; skin soft tissue infections
