What is the significance of a normal Vancomycin (Vancomycin) pre-dose level?

From the Guidelines

The normal pre-dose (trough) level for vancomycin is recommended to be 15-20 mg/L, especially for severe infections like meningitis, and hospital-acquired pneumonia caused by S. aureus, as stated in the guidelines by the Infectious Diseases Society of America 1. This recommendation is based on the need to achieve an AUC/MIC of 1400 for most patients if the MIC is ≤1 mg/L.

• For patients with normal renal function, vancomycin dosages of 15–20 mg/kg (based on actual body weight) given every 8–12 h are required to achieve the suggested trough serum concentrations when the MIC is ≤1 mg/L 1.
• Trough serum vancomycin concentrations should be measured just before the fourth dose (at steady state) when the patient is on a stable dosing regimen, and individual pharmacokinetic adjustments and verification of achievement of target serum concentrations are recommended 1.
• More recent guidelines also support the use of higher trough levels, with a recommendation of 15-20 mg/L for optimal outcomes in critically ill patients with sepsis and septic shock 1.
• A loading dose of 25–30 mg/kg (based on actual body weight) is suggested to rapidly achieve the target trough drug concentration in patients with sepsis and septic shock 1. However, the most recent and highest quality study, which is from 2017, supports the recommendation of a trough level of 15-20 mg/L for vancomycin, especially in critically ill patients 1.

From the FDA Drug Label

In subjects with normal kidney function, multiple intravenous dosing of 1 g of vancomycin (15 mg/kg) infused over 60 minutes produces mean plasma concentrations of approximately 63 mcg/mL immediately after the completion of infusion, mean plasma concentrations of approximately 23 mcg/mL 2 hours after infusion, and mean plasma concentrations of approximately 8 mcg/mL 11 hours after the end of the infusion.

The normal pre-dose level of vancomycin is not explicitly stated in the provided drug label. However, based on the information provided, we can infer that the trough level (pre-dose level) should be around 10-15 mcg/mL or less, as the mean plasma concentration 11 hours after the end of the infusion is approximately 8 mcg/mL 2.

• Key points:
  • The drug label does not provide a specific pre-dose level for vancomycin.
  • The trough level should be around 10-15 mcg/mL or less.
  • Vancomycin levels should be monitored to ensure efficacy and prevent toxicity.

From the Research

Vancomycin Pre-Dose Level Normal

• The normal vancomycin pre-dose level is not explicitly stated in the provided studies, but the therapeutic guidelines recommend a trough concentration of 15-20 mg/L as a therapeutic goal for adult patients with severe infections 3.
• The studies suggest that vancomycin dosing and monitoring practices are not optimized, and there is a need for more effective strategies to improve the efficiency of vancomycin dosing while avoiding the risk of nephrotoxicity 3, 4.
• The current vancomycin therapeutic guidelines recommend empiric doses of 15-20 mg/kg administered by intermittent infusion every 8-12 h in patients with normal kidney function 3.
• Continuous infusion (CI) vancomycin therapy offers the advantage of steady-state serum concentrations (Css) monitoring, thus avoiding the variabilities associated with the timing of trough levels 4.
• The target Css for CI vancomycin therapy is about 20-30 mg/L, and the daily dose is determined by multiplying vancomycin clearance (in L/h) by the desired area under the concentration-time curve (AUC24) 4.

Factors Associated with Nephrotoxicity

• Nephrotoxicity is a significant concern with vancomycin therapy, and several factors are associated with an increased risk of nephrotoxicity, including creatinine clearance <80 mL/min, vancomycin treatment, congestive heart failure, endocarditis, and basal creatinine clearance <80 mL/min 5, 6, 7.
• The risk of nephrotoxicity is higher with vancomycin than with daptomycin, despite poorer basal renal status in the daptomycin group 5.
• Vancomycin use is associated with a higher risk of acute kidney injury (AKI) when serum levels exceed >20 mg/L 7.

Monitoring and Dosing Strategies

• The studies suggest that monitoring steady-state serum concentrations (Css) during continuous infusion (CI) vancomycin therapy may be more effective than monitoring trough concentrations during intermittent infusion (II) 4.
• A new CI vancomycin dosing chart includes clearance-based dosing recommendations for Css values ranging from 17.5 to 27.5 mg/L or AUC24 values ranging from 420 to 660 mg*h/L 4.
• Therapeutic drug monitoring is essential to minimize the risk of nephrotoxicity and optimize vancomycin dosing 3, 4, 7.