When is the optimal time to obtain a trough level for therapeutic drug monitoring (TDM)?

From the Guidelines

The best time to take a trough drug level is immediately before the next scheduled dose of medication, typically within 30 minutes prior to administration, or just before the fourth dose at steady-state conditions, as recommended for vancomycin 1. This timing captures the lowest concentration of the drug in the bloodstream, which occurs just before the next dose is given. For example, if a patient takes vancomycin every 12 hours at 8 AM and 8 PM, the trough level should be drawn shortly before the 8 AM or 8 PM dose. For medications like aminoglycosides (gentamicin, tobramycin), anticonvulsants (phenytoin, carbamazepine), immunosuppressants (tacrolimus, cyclosporine), and antibiotics (vancomycin), accurate trough measurements are essential for proper dosing adjustments. When collecting the sample, it's important to document the exact time of the last dose and when the sample was drawn. Trough levels are particularly valuable because they help prevent toxicity while ensuring therapeutic efficacy, as the lowest drug concentration must remain above the minimum effective level to maintain continuous therapeutic effect throughout the dosing interval. Some studies suggest that for vancomycin, trough serum concentrations of 15–20 mg/L are recommended for certain infections, and that trough serum vancomycin concentrations should be obtained just before the fourth dose, at steady-state conditions 1. However, the most recent and highest quality study on this topic is from 2017, which recommends pre-dose monitoring of trough concentrations for vancomycin, and suggests an IV loading dose of 25–30 mg/kg to rapidly achieve the target trough drug concentration 1. Key points to consider when taking a trough drug level include:

• The timing of the sample collection, which should be immediately before the next scheduled dose
• The documentation of the exact time of the last dose and when the sample was drawn
• The type of medication being monitored, as different medications have different required plasma targets for optimal outcomes
• The patient's renal function, as this can affect the frequency of administration and/or total daily dose of the medication.

From the Research

Trough Drug Level Timing

• The best time to take a trough drug level is not explicitly stated in the provided studies, but it can be inferred that trough levels are typically drawn after 4-6 doses of vancomycin, as seen in the study by 2.
• The study by 2 also mentions that the duration of vancomycin therapy was 8.0 (6.0,15.0) days, and targeted trough vancomycin concentrations were achieved in only 30.9% of all cases.
• Another study by 3 compared clinical outcomes and costs in patients treated with vancomycin targeting trough concentrations of 15-20 mg/L versus those targeting trough concentrations of 5-20 mg/L, but does not specify the timing of trough level draws.

Factors Influencing Trough Levels

• The study by 2 found that age, multiple comorbidities, and diuretic usage affected trough serum vancomycin concentrations.
• The study by 3 found that higher vancomycin trough concentrations improved outcomes in patients with complicated MRSA bacteremia.
• The study by 4 found that AUC-guided TDM had a lower risk of nephrotoxicity compared to trough-guided TDM.
• The study by 5 found that vancomycin AUC below 600 mg·h/L in combination with gentamicin trough level at least below 2 µg/mL may not be reliable indices to reduce the risk of AKI in patients treated with concomitant vancomycin and gentamicin.
• The study by 6 found that AUC-guided dosing strategies were associated with significantly less vancomycin-induced AKI than trough-guided strategies.

Monitoring and Dosing Strategies

• The study by 4 suggests that AUC-guided TDM may be a better approach than trough-guided TDM for monitoring vancomycin levels.
• The study by 6 supports the use of AUC-guided dosing strategies to reduce the risk of vancomycin-induced AKI.
• The study by 5 highlights the importance of considering the combination of vancomycin and gentamicin when monitoring for AKI risk.