When to check vancomycin (Vancomycin) trough levels in patients with Impaired renal function?

From the Guidelines

Vancomycin trough levels should be checked just before the fourth dose for patients receiving prolonged courses of vancomycin treatment. This recommendation is based on the guidelines from the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists, as outlined in the study published in Clinical Infectious Diseases in 2009 1.

Key Points to Consider

• The target trough concentration for most patients is 15–20 mg/L for severe infections such as meningitis and hospital-acquired pneumonia caused by S. aureus, as this range is expected 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.
• Frequent monitoring for short-course therapy (≤5 days) or for lower-intensity dosing (targeted to attain trough serum vancomycin concentrations of ≤15 mg/L) is not recommended.
• Individual pharmacokinetic adjustments and verification of achievement of target serum concentrations are recommended, especially when individual doses exceed 1 g, as the infusion period should be extended to 1.5–2 h in such cases.

Clinical Application

• It is crucial to note that currently available nomograms were not developed to achieve these targeted end points, highlighting the need for individualized pharmacokinetic adjustments.
• The timing of trough level measurement is critical, as checking too early can lead to falsely low readings and inappropriate dose adjustments.
• Monitoring vancomycin trough levels is essential to prevent both treatment failure from subtherapeutic levels and toxicity from excessive levels, particularly nephrotoxicity and ototoxicity, as noted in the guidelines 1.

From the FDA Drug Label

Close monitoring of serum concentrations of vancomycin may be warranted in these patients. Measurement of vancomycin serum concentrations can be helpful in optimizing therapy, especially in seriously ill patients with changing renal function.

Vancomycin Trough Monitoring:

• The FDA drug label recommends close monitoring of serum concentrations of vancomycin in certain patients, such as those with impaired renal function or seriously ill patients with changing renal function.
• The label suggests that measurement of vancomycin serum concentrations can be helpful in optimizing therapy.
• However, the label does not specify exactly when to check vancomycin trough levels.
• As a conservative clinical decision, it is recommended to check vancomycin trough levels before the next dose is administered, typically within 30 minutes before the next dose 2.

From the Research

Vancomycin Trough Levels and Nephrotoxicity

• Vancomycin trough levels are an important factor in determining the risk of nephrotoxicity, with higher trough levels associated with an increased risk of acute kidney injury (AKI) 3, 4, 5, 6.
• A cut-off of 15 mg/L has been suggested as a threshold for detecting AKI, with a sensitivity of 62.6% and a specificity of 65.5% 6.
• A cut-off of 20 mg/L has also been suggested, with a sensitivity of 42.9% and a specificity of 82.5% 6.
• The risk of nephrotoxicity is also increased in patients with certain risk factors, including increasing age, increasing body weight, higher vancomycin dose and frequency, critically ill patients, and site of infection 5.

Monitoring Vancomycin Trough Levels

• The American Society of Health-System Pharmacists recommends monitoring vancomycin trough levels to minimize the risk of nephrotoxicity 7.
• Area under the curve (AUC)-guided dosing strategies have been shown to be associated with a lower incidence of vancomycin-induced AKI compared to trough-guided dosing strategies 7.
• Monitoring vancomycin trough levels is particularly important in patients with risk factors for nephrotoxicity, such as those with pre-existing renal impairment or those receiving concomitant nephrotoxic medications 3, 4.

Timing of Vancomycin Trough Level Checks

• The optimal timing of vancomycin trough level checks is not well established, but it is generally recommended to check trough levels at steady state, which is typically after 3-5 doses 3, 4.
• More frequent monitoring of vancomycin trough levels may be necessary in patients with risk factors for nephrotoxicity or those who are critically ill 5, 6.
• The use of AUC-guided dosing strategies may also require more frequent monitoring of vancomycin trough levels to ensure that the target AUC is achieved 7.