Vancomycin Flashcards
Vancomycin’s Mechanism of Action
Inhibits cross-linking and elongation of peptidoglycan cell wall synthesis by binding D-ala-D-ala terminus
PAE: 2h
Resistant organisms to Vancomycin
VRE
VISA/GISA
VRSA
Tolerance in S.pneumo
vanA Gene Resistance:
- Where was it originally found?
- How does it confer resistance to vancomycin?
- how is it induced and shared?
- VRE
- encodes for VanA: cytoplasmic membrane protein that binds D-Ala-D-Ala terminus, inhibits vancomycin binding
- Cell creates precursors, D-Ala-D-Ser or D-Ala-D-Lactate, that vancomycin cannot bind to
- induced by vancomycin or teichoplanin (resistant to both) and may be plasmid encoded (transposon)
vanB Resistance:
- how does it work?
- how is it induced?
- to what is it still susceptible?
- encodes VanB protein: binds to D-ala-D-ala terminus and inhibits Vancomycin binding (similar to vanA)
- induced by vancomycin ONLY
- still susceptible to teichoplanin
How does tolerance develop for vancomycin?
- Autolysin deficiency
2. Biofilms on foreign devices or tissues
How does VISA confer resistance?
Thickened cell wall due to accumulation of peptidoglycan cell wall components -> vancomycin becomes “trapped” in the thick cell wall
PBP overproduced and compete with vancomycin for precursors
What are heteroresistant S. aureus?
Intermediately resistant subpopulations:
Overall MIC is sensitive, but resistant subpopulation is selected out with vancomycin treatment
Results in therapeutic failure since resistant organisms remain.
What is VRSA?
What is it susceptible to?
Contains vanA gene transfered from VRE
Susceptible to: linezolid, Synercid (quinopristine/dalfopristin), TMP/SMX, tetracycline, minocycline*
*Used in Community acquired
What is spectrum of vanco?
S.aureus, including MRSA S.pneumoniae (100%, including PRSP) Viridans group of Strep (100%) Enterococci (usually with Ag) Many anaerobes -C.difficile -po anaerobes *NOT B.fragilis
Kinetics: Absorption/Distribution
- Where is vanco poorly absorbed?
- Penetration into tissues may be affected by what?
- where are there poor concentrations?
- GIT
- Inflammation and disease state ex. CSF concentrations increase with inflamed meninges
- Lung, especially in lung epithelial lining fluid
Skin in diabetics
Kinetics: Metabolism/Excretion
- Primary excretion method; negligible excretion methods
- Compartment models
- overall, what is the defining feature of vancomycin in terms of distribution and half-life?
- Highly excreted unchanged in urine;
negligible metabolism or biliary excretion - one, two and three compartment models, but use 1 for monitoring
- Distribution and Vd are highly variable; half life is extremely variable too and depends largely on renal function
Adverse effects:
Initial toxicities reported must be taken with a grain of salt. Why?
Early formulations done with “Mississippi Mud”: meaning the product contained many impurities that may have caused the early reports
Vancomycin:
- Most common infusion related adverse effects related most to what feature?
- What is “red man” syndrome?
- What other reactions may occur related to infusion?
- Infusion rate, not serum drug concentrations
- Tingling, flushing of upper torso and face. Related to histamine release from rapid infusion. Solved by giving slower infusion.
- Fever, chills, rigors, phlebitis
- Extravasation -> necrosis
Nephrotoxicity:
- When is there a higher risk of nephrotox?
- risk factors?
- is this very common with vanco?
- When combined with aminoglycosides
- older age; longer tx courses; much higher trough levels
- Uncommon using typical vanco dosage regimens and with monotherapy
Ototoxicity:
- With early reports, why must they be taken with a grain of salt?
- How does the damage progress?
- Reversible?
- What risk factors increases the risk?
- Related to impurities; initial reports related to extremely high serum concentrations
- Starts with tinnitus, loss of high tones first, then gradually to the lower tones
- Not reversible (tinnitus may be reversible if caught early)
- Using with other ototoxic drugs such as Ag, loop diuretics, etc
