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

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Title: Using Japanese big data to investigate novel factors and their high-risk combinations that affect vancomycin-induced nephrotoxicity
Authors: Imai, Shungo Browse this author →KAKEN DB
Kadomura, Shota Browse this author
Miyai, Takayuki Browse this author
Kashiwagi, Hitoshi Browse this author →KAKEN DB
Sato, Yuki Browse this author →KAKEN DB
Sugawara, Mitsuru Browse this author →KAKEN DB
Takekuma, Yoh Browse this author →KAKEN DB
Keywords: electronic medical record database
machine learning
ward pharmacy service
Issue Date: 1-Feb-2022
Publisher: John Wiley & Sons
Journal Title: British Journal of Clinical Pharmacology
Volume: 88
Issue: 7
Start Page: 3241
End Page: 3255
Publisher DOI: 10.1111/bcp.15252
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.
Rights: This is the peer reviewed version of the following article:, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 今井 俊吾

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