Using Japanese big data to investigate novel factors and their high‐risk combinations that affect vancomycin‐induced nephrotoxicity

Abstract

Aims Several factors related to vancomycin‐induced nephrotoxicity (VIN) have not yet been clarified. In the present study, we used Japanese big data to investigate novel factors and their high‐risk combinations that influence VIN. Methods We employed a large Japanese electronic medical record database and included patients who had been administered intravenous vancomycin between June 2000 and December 2020. VIN was defined as an increase in serum creatinine ≥0.5 mg/dL or 1.5‐fold higher than the baseline. The outcomes were: (1) factors affecting VIN that were identified using multiple logistic regression analysis, and (2) combinations of factors that affect the risk of VIN according to a decision tree analysis, which is a typical machine learning method. Results Of the 7306 patients that were enrolled, VIN occurred in 14.2% of them (1035). A multivariate analysis extracted 22 variables as independent factors. Concomitant ramelteon use (odds ratio 0.701, 95% confidence interval 0.512‐0.959), ward pharmacy service (0.741, 0.638‐0.861), duration of VCM < 7 days (0.748, 0.623‐0.899) and trough concentrations 10‐15 mg/L (0.668, 0.556‐0.802) reduce the risk of VIN. Meanwhile, concomitant piperacillin‐tazobactam use (2.056, 1.754‐2.409) and piperacillin use (2.868, 1.298‐6.338) increase the risk. The decision tree analysis showed that a combination of vancomycin trough concentrations ≥20 mg/L and concomitant piperacillin‐tazobactam use was associated with the highest risk. Conclusions We revealed that the concomitant ramelteon use and ward pharmacy service may decrease the risk of VIN, while the concomitant use of not only piperacillin‐tazobactam but also piperacillin may increase the risk.

Risk Factor Analysis of Vancomycin-Induced Nephrotoxicity in Paediatric Patients Aged 0–1 Year Using Japanese Medical Database

“…Database We used RWD database of the Health, Care and Education Information Evaluation and Promotion Institute (HCEI; Kyoto, Japan) with assistance from Real World Data Co., Ltd. (Kyoto, Japan) to collect anonymized medical information derived from electronic medical records. 14) The RWD database contained electronic medical records and claims data of approximately 20 million people from 160 medical institutions. 14,15) Included Patients Our study included VCM-administered and hospitalized patients with estimated age range of 0-1 year between June 2000 and December 2020.…”

Detection of potential drug-drug interactions for risk of acute kidney injury: a population-based case-control study using interpretable machine-learning models

“…In 2000, a case report of two patients who had taken a diuretic, angiotensin receptor blocker, and non-steroidal anti-inflammatory drug (NSAID) in combination, so-called “triple whammy,” and experienced a rise in SCr was published ( Thomas, 2000 ). Subsequently, a number of clinical studies worldwide have investigated whether concurrent use of these drug classes increases SCr level and decreases estimated glomerular filtration rate ( Loboz and Shenfield, 2005 ; Lapi et al, 2013 ; Camin et al, 2015 ; Kunitsu et al, 2019 ; Imai et al, 2022 ). Besides the triple whammy, clinical studies have tried to detect drug-drug interactions between two or more drug classes in acute kidney injury ( Bird et al, 2013 ; Gandhi et al, 2013 ; Gul et al, 2016 ; Inaba et al, 2019 ; Okada et al, 2019 ; Liu et al, 2021 ; Salerno et al, 2021 ).…”

Development and Evaluation of a Novel Software Program, SAKURA-TDM, for Area Under the Concentration-Time Curve–Guided Vancomycin Dosing: A Short Communication

“…9 More recently, an investigational study performed using Japanese big data sets demonstrated that compared with the concentration range of 15–20 mcg/mL (OR 2.587, 95% CI 2.149–3.114), vancomycin trough concentrations of ≥20 mcg/mL were significant independent factors affecting vancomycin-induced nephrotoxicity. 10…”

“…9 More recently, an investigational study performed using Japanese big data sets demonstrated that compared with the concentration range of 15-20 mcg/mL (OR 2.587, 95% CI 2.149-3.114), vancomycin trough concentrations of $20 mcg/mL were significant independent factors affecting vancomycin-induced nephrotoxicity. 10 In this study, we aimed to develop and evaluate a novel software program, SAKURA-TDM ver.1.0 for AUC-guided vancomycin dosing. We also attempted to determine the theoretical cutoff point of steady-state AUC 24 , which could lower the probability of trough values exceeding 20 mcg/mL at the next blood sampling.…”