Clinical and Pharmacokinetic Outcomes of Peak–Trough-Based Versus Trough-Based Vancomycin Therapeutic Drug Monitoring Approaches: A Pragmatic Randomized Controlled Trial

Abstract

BackgroundVancomycin therapeutic drug monitoring (TDM) is based on achieving 24-h area under the concentration–time curve to minimum inhibitory concentration cure breakpoints (AUC24/MIC). Approaches to vancomycin TDM vary, with no head-to-head randomized controlled trial (RCT) comparisons to date.ObjectivesWe aimed to compare clinical and pharmacokinetic outcomes between peak–trough-based and trough-only-based vancomycin TDM approaches and to determine the relationship between vancomycin AUC24/MIC and cure rates.MethodsA multicentered pragmatic parallel-group RCT was conducted in Hamad Medical Corporation hospitals in Qatar. Adult non-dialysis patients initiated on vancomycin were randomized to peak–trough-based or trough-only-based vancomycin TDM. Primary endpoints included vancomycin AUC24/MIC ratio breakpoint for cure and clinical effectiveness (therapeutic cure vs therapeutic failure). Descriptive, inferential, and classification and regression tree (CART) statistical analyses were applied. NONMEM.v.7.3 was used to conduct population pharmacokinetic analyses and AUC24 calculations.ResultsSixty-five patients were enrolled [trough-only-based-TDM (n = 35) and peak–trough-based-TDM (n = 30)]. Peak–trough-based TDM was significantly associated with higher therapeutic cure rates compared to trough-only-based TDM [76.7% vs 48.6%; p value = 0.02]. No statistically significant differences were observed for all-cause mortality, neutropenia, or nephrotoxicity between the two groups. Compared to trough-only-based TDM, peak–trough-based TDM was associated with less vancomycin total daily doses by 12.05 mg/kg/day (p value = 0.027). CART identified creatinine clearance (CLCR), AUC24/MIC, and TDM approach as significant determinants of therapeutic outcomes. All patients [n = 19,100%] with CLCR ≤ 7.85 L/h, AUC24/MIC ≤ 1256, who received peak–trough-based TDM achieved therapeutic cure. AUC24/MIC > 565 was identified to be correlated with cure in trough-only-based TDM recipients [n = 11,84.6%]. No minimum AUC24/MIC breakpoint was detected by CART in the peak–trough-based group.ConclusionMaintenance of target vancomycin exposures and implementation of peak–trough-based vancomycin TDM may improve vancomycin-associated cure rates. Larger scale RCTs are warranted to confirm these findings.

From Therapeutic Drug Monitoring to Model‐Informed Precision Dosing for Antibiotics

“…To determine the AUC in a clinical setting, either a peak and trough sample or Bayesian forecasting using a single sample has been recommended 77 . A recent study found that considering both peak and trough levels showed better therapeutic cure rates compared with only trough levels, although this result requires confirmation in larger studies 79 . Neely and colleagues showed that AUC‐based vs. trough‐based TDM was superior with regard to reduction of nephrotoxicity (<1% vs. 8%), and shorter therapy time (4.7–5.4 vs. 8.2 days) 63 .…”

“…77 A recent study found that considering both peak and trough levels showed better therapeutic cure rates compared with only trough levels, although this result requires confirmation in larger studies. 79 Neely and colleagues showed that AUC-based vs. trough-based TDM was superior with regard to reduction of nephrotoxicity (<1% vs. 8%), and shorter therapy time (4.7-5.4 vs. 8.2 days). 63 Nonetheless, more research is required to potentially further optimize the AUC target for vancomycin, as a recent systematic meta-analysis found that the sensitivity and specificity was 0.77 (95% confidence interval (CI), 0.67-0.84) and 0.62 (95% CI, 0.52-0.71), respectively, for the primary outcome variable mortality.…”

Is Early Monitoring Better? Impact of Early Vancomycin Exposure on Treatment Outcomes and Nephrotoxicity in Patients with Methicillin-Resistant Staphylococcus aureus Infections

“…The study suggested that a TDM-guided Bayesian-based approach should be considered an invaluable tool for clinicians to appropriately monitor real-time vancomycin therapy in critically ill patients [ 17 ]. In this study, peak and trough vancomycin concentrations were measured in over half the patients for whom the previous study showed peak-trough based vancomycin TDM improved the therapeutic cure rate [ 18 ].…”

Survey on request form content and result reporting in therapeutic drug monitoring service among laboratories in Czechia and Slovakia

“…Al-Sulaiti reported the importance of peak drug concentration for vancomycin dosing. Peak-trough TDM approach improves the vancomycin-associated cure rate in patients treated with vancomycin for Gram-positive infections (12). The correct timing of blood draw is the major practical problem of the interpretation of peak plasma drug concentrations.…”