Vancomycin Flashcards
Vancomycin MOA
-inhibits cell wall synthesis by binding D-alanyl-D-alanine portion of cell wall precursors
= prevents cross-linking and further elongation of peptidoglycan strucutre
= weakens cell wall
=lysis (bactericidal)
Vancomycin targets
-gram + pathogens
-MRSA, stept, listeria
-high resistance in enterococcus f
-c. diff give orally bc GI infection
Vancomycin adverse effects
-nephrotoxicity/ototoxicity
-infusion issues (histamine release)
-local phlebitis
-hypersensitivity, Stevens Johnson Syndrome
-Thrombocytopenia (prolonged admin)
Vancomycin PK
-poorly absorbed PO
-must admin IV for systemic infections (NOT IM)
-longer distributions phase (1-2 hours)
-Vd = 0.7 L/kg
-50% protein binding
-renal elimination
-6-12h t1/2
-removed by high-flux hemodialysis (10%/h, admin dose after dialysis on dialysis days)
Vancomycin PD
-time-dependent activity
-PD target: Auc/MIC
-goal AUC/MIC= 400-600mg*h/L (assuming MIC of 1mcg/mL)
elevated AUC of vancomycin
-AUC >600-700mg*h/L
-prolonged is risk factor for nephrotoxicity
-high AUC during first 48 hours inc risk 3-4x
Vancomycin loading dose
-20-35mg/kg based on total body weight in critically ill pt
-do not exceed 3000mg
-25mg/kg is good dose
Vancomycin maintenance dose
-15-20mg/kg q8-12h based on total BW in pt with NORMAL renal function
Vancomycin max infusion rate
-10-15mg/min
-1000mg takes about an hour
-2000mg takes about 2 hours
-some might need slower
Vancomycin dosing interval
-dependent on renal function CrCL
Loading dose
-useful to rapidly achieve targeted serum concentrations and dec risk of subtherapeutic concentrations
-pt do NOT achieve SS faster!! that shit is dependent on half life!!
Loading dose recommended for
-critically ill/ICU
-dialysis/renal replacemnt therapy
-initiating continuous infusion dosing
Vancomycin intitial dosing intervals based on CrCl
-120: 12
-100:12-18
-80: 18
-60: 24
-40: 36
-20: 60
Vancomycin Vd=
0.7L/kg
Vancomycin maintenance dosing
-15-20mg/kg using TBW
-15 if 120-200kg, use 0.6L/kg Vd
-q8-12h if <30 and >100ml/min CrCl
-12-18h if >60
-q24 for 40-49
-q36-48h 25-39
-intermittent is <25
-consider q8h for pt w fast drug clearance: cystic fibrosis, thermal burn injury, trauma, IV drug users
Vancomycin monitoring
-AUC/MIC over 24 h = 400-600
-maintain trough concentrations > 10mcg/mL
Vancomycin loading dose
-20-35mg/kg ABW
-max 3000mg
Vancomycin monitoring methods (2)
-obtain 2 concentrations at or near Css (peak around 1-2 hours after infusion)
-SAWCHUK-ZASKE FIRST ORDER to determine AUC and optimal dose
-use BAYESIAN software and obtain 1-2 concentration with at least one trough
-preferred: 2 samples shortly after and right before end of interval (pt doesnt have to be at Css)
Two compartment model
-inc during infusion
-distribution, elimination
Initial dosing using population parameters
- select desired Cmax and Cmin to achieve target AUC
- calc IBW, AdjBW, LBW prn
- estimate CrCl (Cockcroft-Gault)
- estimate elimination (k)
- half-life
- Vd
- tau
- MD to nearest 250mg
- double check
- AUC
Initial vancomycin dosing in practice
-dose based on mg/kg and interval on CrCl
-or
-population dosing to calc INITIAL regimen
Cmax, Cmin targets
-30-35 mcg/mL
-10-15 mcg/mL
use adjBW in vancomycin when
-TBW >1.3IBW
-use LBW if obese (BMI>40)
Cockroft-gault
-estimates CrCl
-if TBW < IBW use TBW
-LBW if obese
-CR comes from. muscle, need good estimate of lean mass
Sawchuk-Zaske Method
- verify
when to begin new infusion regimen
t equation
-number of hours to wait from PEAK to beginning new regimen
-on the hour no half hour
Continuous Infusion (CI) dosing
-Ci is reasonable alt
-simililar/reduced risk of nephrotoxicity
-LD: 15-20 mg/kg
-MD: 30-40 mg/kg up to 60mg/kg
-Css 20-25mcg/mL
-need dedicated IV line
-fewer blood samples, obtain blood sample at any time
-more rapid attainment of desired concentrations
24 hour dose of CI dosing
-24h dose = desired AUC24 by Cl (v*k)
