Abstract
BACKGROUND: The aim of this study was to identify the clinical factors associated with serum trough concentrations of vancomycin crystalline degradation product (CDP-1) and to determine the impact of CDP-1 on chemiluminescence microparticle immunoassay (CMIA) results among patients with chronic kidney disease (CKD). METHODS: In this retrospective observational study, patients with CKD who were receiving vancomycin intravenously were included if steady-state serum trough levels of vancomycin were available. Patients were allocated to three groups on the basis of their estimated creatinine clearance (eCrCl) on the day of trough level monitoring: G1 (60 < eCrCl ≤ 90 mL/min), G2 (30 < eCrCl ≤ 60 mL/min), and G3 (eCrCl ≤ 30 mL/min). CDP-1 serum concentrations were determined via ultra-high performance liquid chromatography‒tandem mass spectrometry (UPLC‒MS/MS). Vancomycin serum concentrations measured via CMIA were compared with those measured via UPLC‒MS/MS. Multiple linear regression analyses were performed to identify factors associated with the CDP-1 concentration and the ratio of vancomycin concentration determined via CMIA to vancomycin concentration via UPLC‒MS/MS (V(CMIA)/V(UPLC-MS/MS)). RESULTS: Among the 167 patients included, 49 (29.34%), 69 (41.32%), and 49 (29.34%) were allocated to G1, G2, and G3, respectively. There were significant differences in the CDP-1 trough concentrations and V(CMIA/)V(UPLC-MS/MS) ratios between the three groups. In the multivariate analysis, eCrCl levels (P < 0.001), the time interval from the initial dose to the trough level (P < 0.001), and vancomycin dose (P < 0.001) were associated with CDP-1 trough concentrations. The CDP-1 trough concentration was positively associated with the V(CMIA)/V(UPLC-MS/MS) ratio (P = 0.002). CONCLUSIONS: Delayed timing of trough level sampling could contribute to increased CDP-1 levels and the overestimation of vancomycin levels, especially in patients with severe deterioration in renal function. It may be necessary to increase the frequency of TDM and select quantitative methods to measure vancomycin serum levels without interfering with CDP-1.