Vancomycin is a glycopeptide antibiotic commonly used to treat serious infections caused by Gram-positive bacteria, especially Staphylococcus aureus including MRSA.
The two biggest drawbacks to the use of Vancomycin are:
1) The narrow therapeutic window, i.e. a small range between efficacy and toxicity
2) The difficulty in getting a patient’s blood levels up to therapeutic levels quickly enough, especially when they are septic
The old regime was to use a dose of 1g BD for patients with normal renal function under 65 years old, and 1g OD if they were over 65 years old. Patients with renal failure were given 1g and then re-dosed when their levels were <15mg/L. In practice many microbiologists used to dose younger adults at much higher levels, often 1.25g BD or higher because these patients didn’t reach therapeutic levels on the old regime.
The two biggest drawbacks to the use of Vancomycin are:
1) The narrow therapeutic window, i.e. a small range between efficacy and toxicity
2) The difficulty in getting a patient’s blood levels up to therapeutic levels quickly enough, especially when they are septic
The old regime was to use a dose of 1g BD for patients with normal renal function under 65 years old, and 1g OD if they were over 65 years old. Patients with renal failure were given 1g and then re-dosed when their levels were <15mg/L. In practice many microbiologists used to dose younger adults at much higher levels, often 1.25g BD or higher because these patients didn’t reach therapeutic levels on the old regime.
There is new guidance from both the UK and USA based upon expert opinion that advises us to
use Vancomycin differently. This involves giving an initial loading dose to get patients up to therapeutic levels quickly, and then a dosing regimen specifically based upon their calculated Creatinine Clearance. WARNING: the guideline from the Scottish Antimicrobial Prescribing Group’s “Intravenous Vancomycin Use in Adults Intermittent (Pulsed) Infusion and the Infectious Diseases Society of America is a lot more complicated than before, however read on for 3 easy steps!
New trough levels are also proposed, 10-20mg/L, to avoid the development of Vancomycin resistance in Staphylococcus sp. which may occur due to using low antibiotic levels, e.g. 5mg/L. Previously Microbiologists have advised using 5mg/L for bacteria which have an MIC of ≤1mg/L. However as MIC is usually not known by the clinician, it may be unclear that a Microbiologist has advised this lower dose knowing the MIC. Therefore using 5mg/L is no longer recommended in the guidelines. In time, I believe this may need to be re-evaluated, as the current evidence is only based upon Staphylococci rather than other Gram-positive bacteria such as Streptococci. It may be that using Vancomycin at high levels to treat these other Gram-positive bacteria causes an unacceptable risk of toxicity.
The 3 Easy Steps to the new guidance on Vancomycin are as follows:
Step 1: Give a Loading Dose
This is based on Actual Body Weight
use Vancomycin differently. This involves giving an initial loading dose to get patients up to therapeutic levels quickly, and then a dosing regimen specifically based upon their calculated Creatinine Clearance. WARNING: the guideline from the Scottish Antimicrobial Prescribing Group’s “Intravenous Vancomycin Use in Adults Intermittent (Pulsed) Infusion and the Infectious Diseases Society of America is a lot more complicated than before, however read on for 3 easy steps!
New trough levels are also proposed, 10-20mg/L, to avoid the development of Vancomycin resistance in Staphylococcus sp. which may occur due to using low antibiotic levels, e.g. 5mg/L. Previously Microbiologists have advised using 5mg/L for bacteria which have an MIC of ≤1mg/L. However as MIC is usually not known by the clinician, it may be unclear that a Microbiologist has advised this lower dose knowing the MIC. Therefore using 5mg/L is no longer recommended in the guidelines. In time, I believe this may need to be re-evaluated, as the current evidence is only based upon Staphylococci rather than other Gram-positive bacteria such as Streptococci. It may be that using Vancomycin at high levels to treat these other Gram-positive bacteria causes an unacceptable risk of toxicity.
The 3 Easy Steps to the new guidance on Vancomycin are as follows:
Step 1: Give a Loading Dose
This is based on Actual Body Weight
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Step 2: Give the Maintenance Dose
The dose and frequency is based on the Calculated Creatinine Clearance (CrCl). Dose Intervals are either 12, 24 or 48 hours after the Loading Dose.
Use the Cockcroft Gault equation to give a Calculated Creatinine Clearance (CrCl)
The dose and frequency is based on the Calculated Creatinine Clearance (CrCl). Dose Intervals are either 12, 24 or 48 hours after the Loading Dose.
Use the Cockcroft Gault equation to give a Calculated Creatinine Clearance (CrCl)
Click for larger image
WARNING: you MUST use the CALCULATED CREATININE CLEARANCE figure not the Creatinine value as the Creatine value does not give an accurate reflection of renal function on its own.
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Try these examples:
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Try again:
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Step 3: Measure the Trough Level
A Trough level should be taken within 48 hours of starting treatment (e.g. just before the 4th Maintenance Dose if on 12 hourly Dose Interval or just before the 1st Maintenance Dose if on 48 hourly Dose Interval), THEN at least every 3 days if stable renal function, to reach the target 10-20mg/L
(15-20mg/L in severe or deep-seated infections).
Note: Take Trough levels more frequently (i.e. just before every dose) in changing renal function.
A Trough level should be taken within 48 hours of starting treatment (e.g. just before the 4th Maintenance Dose if on 12 hourly Dose Interval or just before the 1st Maintenance Dose if on 48 hourly Dose Interval), THEN at least every 3 days if stable renal function, to reach the target 10-20mg/L
(15-20mg/L in severe or deep-seated infections).
Note: Take Trough levels more frequently (i.e. just before every dose) in changing renal function.
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Test yourself:
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Whilst this may appear more complicated the new regime should benefit patients by making sure they achieve therapeutic levels of Vancomycin as quickly as possible.
BE AWARE the new dosing regimen does have a potential drawback. In a comparison study (Ref. 2) of the predicted trough levels comparing the old regime to the new regime, a small number of patients (3%) were predicted to have potentially toxic levels (>20mg/L) with this new regime compared to the old. However, the new regime ensures a much higher proportion of patients (77%) achieved therapeutic levels (10-20mg/L) at the time of their first trough level compared with the old regime (26%). This on balance has swung the guidance in favour of the new regime.
References
BE AWARE the new dosing regimen does have a potential drawback. In a comparison study (Ref. 2) of the predicted trough levels comparing the old regime to the new regime, a small number of patients (3%) were predicted to have potentially toxic levels (>20mg/L) with this new regime compared to the old. However, the new regime ensures a much higher proportion of patients (77%) achieved therapeutic levels (10-20mg/L) at the time of their first trough level compared with the old regime (26%). This on balance has swung the guidance in favour of the new regime.
References
- Scottish Antimicrobial Prescribing Group, Intravenous Vancomycin Use in Adults Intermittent (Pulsed) Infusion 2013
- Development and evaluation of vancomycin dosage guidelines designed to achieve new target concentrations. Thomson A, Staatz C, Tobin C
et al. J Antimicrob Chemother 2009; 63: 1050-1057 - Therapeutic monitoring of vancomycin in adult patients: A consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious
Diseases Pharmacists. Rybak M, Lomaestro B, Rotschafer J et al. Am J Health-Syst Pharm 2009; 66: 82-98
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