VANCOMYCIN REVIEW
Eddie Grace, Pharm.D., BCPS, AQ-ID, AAHIVE
Associate Professor of Pharmacy Practice
Presbyterian College School of Pharmacy
OBJECTIVES
Review the pharmacokinetics of vancomycin
Review the 2009 IDSA/SIDP Vancomycin
guidelines
Target trough levels for various infections
When to draw trough levels
AUC/MIC importance
Dosage adjustments based on trough levels
Estimation of AUC/MIC ratio
Importance of loading dose
Discussion of possible vancomycin study
PHARMACOKINETICS OF VANCOMYCIN
Volume of distribution
VCN is hydrophilic
Vd ranges from 0.5L/Kg to 1.2L/Kg
Often 0.7 L/Kg TBW is used
In obese patients:
30% of adipose tissue contains water
Additional weight is due to increased adipose tissue, muscle
mass, and connective tissue
Vd in obese patients 0.3-0.8 L/Kg TBW based on published
studies
VCN PHARMACOKINETICS
Vancomycin Clearance
Based on estimated creatinine clearance
Most studies advocate use of the Cockgroft-Gault
Equation utilizing TBW
Round serum creatinine to 1.0 if patient elderly, bed ridden,
or amputee
Multiple result by 0.85 if female
Consider use of AdBW in obese patients
Most estimations of vancomycin clearance based on
population PK parameters and values
VCN PHARMACOKINTICS
VCN is approximately 55% protein bound in
plasma
Bound to AAG (based on primary evidence)
AAG increases with infection and trama
% bound to AAG remains constant but amount of AAG
increases with certain triggers
Some studies have shown a correlation between
albumin levels and SVC.
Low albumin (<3) may result in elevated free SVC
BACTERIOCIDAL VS BACTERIOSTATIC
BACTERIOCIDAL VS BACTERIOSTATIC
VANCOMYCIN
Glycopeptide antibacterial
Bacteriocidal against Staphylococcus and
Enterococcus species
Weaker bacteriocidal activity against
Streptococcus species
Orally active against Clostridium difficile
Inadequate concentrations in the gastro-intestinal
tract if given intravenously
VANCOMYCIN
Vancomycin bacteriocidial effect is present when
concentration is 4 x MIC
MRSA is considered susceptible to vancomycin if
the MIC is 2
Vancomycin penetration to the lung is 5-40% and
concentration in ELF compared to plasma is 15%
If MIC is 1 bacteriocidal concentration in lung
= 4 therapeutic level in plasma 16-20
If MIC is 2 would require a trough of 32-40
HIGH risk of toxicity
Consider alternative agent
TARGET TROUGHS
Vancomycin trough should ALWAYS be >
10mg/L to prevent the development of resistance
Even if MRSA MIC is 0.5 for vancomycin
When using vancomycin empirically, assume
MRSA MIC is 1 for vancomycin until proven
otherwise
VANCOMYCIN TARGET TROUGHS
Target trough of 15-20mg/L for:
EMPIRIC therapy
Fever of unknown origin (FUO)
Febrile neutropenia
Community/Healthcare-associated pneumonia
Bacteremia/sepsis
Osteomyelitis
Diabetic wound infections
Endocarditis
Meningitis
If MRSA MIC for vancomycin is 1
UTILIZING A LOADING DOSE
IDSA/SIDP guidelines recommend a loading dose
in seriously ill patients
Utilized to reach steady-state like
concentrations after the first dose
Recommended loading dose is 25-30mg/Kg based
on ACTUAL body weight
15-20mg/Kg is NOT considered a loading dose
In obese patients, one may consider a max dose of
2500mg as loading dose and move-up the second
dose
EXAMPLE OF LOADING DOSE IN OBESE
PATIENT
Tau
Tau
20
15
WHEN TO CHECK VANCOMYCIN TROUGH
A trough should be checked:
Prior to 4th dose (after 3rd dose)
85-90% steady-state if no loading dose utilized
~100% steady-state if loading dose utilized
If renal function is unstable
If dosage adjustment is made, trough can be checked
after 3 doses
If toxicity is suspected such as nephrotoxicity or
ototoxicity
Changes in albumin level (if albumin <3) while pt is
on vancomycin therapy
ALBUMIN AND VANCOMYCIN TROUGH
Vancomycin is 50-55% protein bound to AAG
Hypoalbuminenmia may result in elevated free
vancomycin concentrations
If albumin is < 3.0, consider decreasing dose by
500mg
Rounding SCR in CrCl calculation helps adjust
for low albumin levels
MONITORING VANCOMYCIN EFFICACY
Serum vancomycin trough levels can be checked
at steady-state to ensure efficacy
10-15 mg/L
15-20 mg/L
AUC to MIC ratio is the recommended method of
determining vancomycin efficacy
AUC: MIC of >400 ensures efficacy
CALCULATING AUC:MIC
SIMPLIFIED
1.
2.
3.
4.
5.
Calculate CrCl
Select correct vancomycin dose and interval
Calculate Vancomycin Clearance (VCl)
Calculate average daily dose (ADD)
Estimate AUC:MIC
CALCULATING AUC:MIC
CALCULATE CREATININE CLEARANCE
Using Cockcroft-Gault Equation
Round SCR to 1.0 if < 1.0 in patients who are:
Elderly
Physically inactive
Immobile/bed ridden
Low serum albumin
Amputee
Use total body weight except in obese patient
who are > 140% of IBW at which time use
adjusted body weight
AdBW = (IBW + (0.4 x [TBW-IBW])
CALCULATING AUC:MIC
SELECT CORRECT DOSE AND INTERVAL
ESTIMATE VANCOMYCIN CLEARANCE
Vancomycin clearance can be estimated using
various published methods
A simple method to estimate VCL:
VCL = CrCL x A
A = to 0.7 to 0.8 in non-obese individuals
A = 0.9 to 1.1 in obese individuals
ESTIMATING ADD
Average daily dose reflects the amount of
vancomycin administered over a period of 24
hours.
Dose
_________________
Dosing interval
x 24
= ADD
ESTIMATING AUC:MIC
SUMMARY OF AUC:MIC
AUC:MIC AND NO LOADING DOSE
AUC:MIC AND LOADING DOSE
