Validation of Vancomycin Area under the Concentration—Time Curve Estimation by the Bayesian Approach Using One-Point Samples for Predicting Clinical Outcomes in Patients with Methicillin-Resistant Staphylococcus aureus Infections

Abstract

Area under the concentration–time curve (AUC)-guided vancomycin treatment is associated with decreased nephrotoxicity. It is preferable to obtain two samples to estimate the AUC. This study examined the usefulness of AUC estimation via trough concentration (Cmin)-only sampling of 260 adults infected with methicillin-resistant Staphylococcus aureus (MRSA) who received vancomycin. The exact Cmin sampling time was used for Bayesian estimation. A significantly higher early treatment response was observed in patients with a day 2 AUC ≥ 400 µg·h/mL than those with <400 µg·h/mL, and a significantly higher early nephrotoxicity rate was observed in patients with a day 2 AUC ≥ 600 µg·h/mL than those with <600 µg·h/mL. These AUC cutoff values constituted independent factors for each outcome. In sub-analysis, the discrimination ability for early clinical outcomes using these AUC cutoffs was confirmed only in patients with q12 vancomycin administration. A significant difference in early treatment response using the 400 µg·h/mL cutoff was obtained only in patients with low-risk infections. The usefulness of the vancomycin AUC target to decrease nephrotoxicity while assuring clinical efficacy was even confirmed with a single Cmin measurement. However, assessment with two samples might be required in patients with q24 administration or high/moderate-risk MRSA infections.

Clinical Practice Guidelines for Therapeutic Drug Monitoring of Vancomycin in the Framework of Model-Informed Precision Dosing: A Consensus Review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring

“…Population PK models can serve as a quantitative PK framework in MIPD. Population PK models are used to guide initial therapeutic decision making (population PK model-guided dosing) [ 54 , 58 , 61 , 62 , 63 ]. Population PK model-guided dosing is optimised to dosing based on the Bayesian posterior probability using the observed individual patient PK/pharmacodynamic (PD) information (Bayesian estimation using the measured concentration combined with a population PK model) [ 56 , 64 , 65 ].…”

“…Population PK models are used to guide initial therapeutic decision making (population PK model-guided dosing) [ 54 , 58 , 61 , 62 , 63 ].…”

“… MIPD offers prompt AUC calculation for the management of MRSA infections, in which AUC/MIC is recommended for use as the PK/PD target [ 3 , 17 , 57 , 58 , 59 , 60 ]. MIPD proposes AUCs on days 1 and 2 and at steady state irrespective of the day of TDM, and the antimicrobial stewardship team can select any of these AUCs to achieve the target range according to their needs [ 18 , 54 ]. MIPD does not require steady state to be reached, and earlier concentration data are available than obtained using traditional TDM for the adjustment of vancomycin dosing.…”

“…MIPD proposes AUCs on days 1 and 2 and at steady state irrespective of the day of TDM, and the antimicrobial stewardship team can select any of these AUCs to achieve the target range according to their needs [ 18 , 54 ].…”

“…Timing of TDM (for CQ 5): AUC on days 1 and day 2 and at steady state was evaluated using PAT in 260 patients with MRSA infections, and the relationships of AUC on day 2 with early treatment response and AKI were studied [ 54 ].…”