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