There are multiple studies investigating the therapeutic dosing of vancomycin and the associated incidence of AKI. Previous studies have correlated vancomycin AUC/MICs of 400 mg to 600 mg × h/L with clinical effectiveness.2,6 In 2017, Neely and colleagues looked at the therapeutic dosing of vancomycin in 252 adults with ≥ 1 vancomycin level.7 During this prospective trial, they evaluated patients for 1 year and targeted trough concentrations of 10 to 20 mg/L with infection-specific goal ranges of 10 to 15 mg/L and 15 to 20 mg/L for noninvasive and invasive infections, respectively. They also targeted AUC/MIC ratios ≥ 400 mg × h/L regardless of trough concentration using Bayesian estimated AUC/MICs for 2 years. They found only 19% of trough concentrations to be therapeutic compared with 70% of AUC/MICs. A secondary outcome assessed by Neely and colleagues was nephrotoxicity, which was identified in 8% of patients with trough targets and 2% of patients with AUC/MIC targets.8
Previous studies evaluating the use of vancomycin in the veteran population have focused on AKI incidence, general nephrotoxicity, and 30-day readmission rates.4,7,9,10 Poston-Blahnik and colleagues investigated the rates of AKI in 200 veterans using AUC/MIC-guided vancomycin TDM.5 They found an AKI incidence of 42% of patients with AUC/MICs ≥ 550 mg × h/L and 2% of patients with AUC/MICs < 550 mg × h/L.5 Gyamlani and colleagues investigated the rates of AKI in 33,527 veterans and found that serum vancomycin trough levels ≥ 20 mg/L were associated with a higher risk of AKI.8 Prabaker and colleagues investigated the association between vancomycin trough levels and nephrotoxicity, defined as 0.5 mg/L or a 50% increase in serum creatinine (sCr) in 348 veterans. They found nephrotoxicity in 8.9% of patients.10 Patel and colleagues investigated the effect of AKI on 30-day readmission rates in 216 veterans.10 AKI occurred in 8.8% of patients and of those 19.4% were readmitted within 30 days.10 Current literature lacks evidence regarding the comparison of the safety and efficacy of vancomycin trough-guided vs AUC/MIC-guided TDM in the veteran population. Therefore, the objective of this study was to investigate the differences in the safety and efficacy of vancomycin TDM in the veteran population based on the different monitoring methods used.
METHODS
This study was a retrospective, single-center, quasi-experimental chart review conducted at the Sioux Falls Veterans Affairs Health Care System (SFVAHCS) in South Dakota. Data were collected from the Computerized Patient Record System (CPRS). The SFVAHCS transitioned from trough-guided to AUC/MIC-guided TDM in November 2020.
Patients included in this study were veterans aged ≥ 18 years with orders for parenteral vancomycin between February 1, 2020, and October 31, 2020, for the trough-guided TDM group and between December 1, 2020, and August 31, 2021, for the AUC/MIC-guided TDM group. Patients with vancomycin courses initiated during November 2020 were excluded as both TDM methods were being used at that time. Patients were excluded if their vancomycin course began before February 1, 2020, for the trough-guided TDM group or began during November 2020 for the AUC/MIC-guided TDM group. Patients were excluded if their vancomycin course extended past October 31, 2020, for the trough group or past August 31, 2021, for the AUC/MIC group. Patients on dialysis or missing Cmax, Cmin, or sCr levels were excluded.
This study evaluated both safety (AKI incidence) and effectiveness (time spent in therapeutic range and time to therapeutic range). The primary endpoint was presence of vancomycin-induced AKI, which was based on the most recent Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition: increased sCr of ≥ 0.3 mg/dL or by 50% from baseline sustained over 48 hours without any other explanation for the change.11 A secondary endpoint was the absence or presence of AKI.
Additional secondary endpoints included the presence of the initial trough or AUC/MIC of each vancomycin course within the therapeutic range and the percentage of all trough levels or AUC/MICs within therapeutic, subtherapeutic, and supratherapeutic ranges. The therapeutic range for AUC/MIC-guided TDM was 400 to 600 mg × h/L and 10 to 20 mg/L depending on indication for trough-guided TDM (15-20 mg/L for severe infections and 10-15 mg/L for less invasive infections). The percentage of trough levels or AUC/MICs within therapeutic, subtherapeutic, and supratherapeutic ranges were calculated as a ratio of levels within each range to total levels taken for each patient.