Vancomycin

Question 1

Vancomycin MOA

Answer 1

Bactericidal
Inhibits cell wall synthesis and assembly at the second stage by binding firmly to D-ala-D-ala portion of the cell wall precursors to prevent cross linking

Question 2

Vancomycin Mechanism of resistance

Answer 2

took over 30 years for vancomycin resistance to emerge

1. Resistance in VRE and VSRA is due to modification of D-ala-D-ala (replaced by D-lactate) - Phenotypes VanA, VanB,
   VanC (chromosomal resistance gene)
2. VISA - (Vancomycin intermediate S. Aureus) resistance due to thickening of cell wall whih required higher doses of vancomycin

Question 3

Vancomycin Spectrum of activity

Answer 3

Gram positive
Streptococcus Pneumonia (PRSP)
Staphylococcus Aureus (MSSA) (MRSA - THE DRUG OF CHOICE)
Coagulase negative staphylococci
Enteroccous faecalis and faecium (only bacteriostatic)
Above Diaphragm anaerobes
C. Difficile

Question 4

Pharmacology

Answer 4

Time dependent
AUC/MIC ratio target 400-600
Interpatient variability in Vd and CL
IV and oral form

Question 4

Absorption

Answer 4

Oral form has terrible absorption but can be used for tx of C. Diff

For any systemic infections must use IV infusion

NO IM

Question 5

Distribution

Answer 5

widely distributed into the body and diffue

Variable penetration into CSf even in presence of inflammed meninges

TBW used for dosing
normal Vd = 0.6-0.7 L/Kg

Takes one hour to distribute from plasma into tissue compartment

Question 6

Elimination

Answer 6

Primarily eliminated unchanged by the kidneys

Elimination half- life depends on renal function (elimination half life increases as renal function decreases)
- 6-8 hours with normal

• Those with end stage renal failure NOT on dialysis elimination half life is 7-14 days

Question 7

Monitoring Serum concentration

Answer 7

Monitor on those who we know will be on vancomycin for directed therapy

Peak should be drawn 60 minutes after the end of infusion

Question 8

Dosing considerations

Answer 8

*TBW (up to around 120 kg) should be used for dosing in obese patients  maximum initial doses should not exceed 2000 mg to 3000 mg

Question 9

Clinical use

Answer 9

1. Infection due to Methicillin resistant staph aureus (MRSA) -THE DRUG OF CHOICE - EXAM Q
2. Serious Gram positive infections in B lactam allergic patients
3. Infections caused by multi-drug resistant Gram positive Bactera (PRSP) (TARGET ORGANSIM)
4. ORAL vancomycin for clostridium difficile colitis

Question 10

Adverse effects

Answer 10

1.Red man syndrome - related to rate of infusion time - Happens within 15 minutes of infusion (can give vancomycin again after this happens but would want to slow down infusion rate or give antihistamines before hand)
2. Nephrotoxicity - Risk factors: those with renal insufficiency, higher doses of vancomycin and higher concentrations, use other nephrotoxic drugs
3. Ototoxicity
4. Thrombophlebitis
5. Interstitial nephritis