Published papers

PURPOSE: Some clinical studies have reported the occurrence of nausea and vomiting with linezolid (LZD) administration. However, no studies have evaluated nausea and vomiting as primary endpoints. In a previous study, we noted a possible relationship between LZD and vomiting, but risk factors were not identified. Therefore, the aim of the present study was to identify them. METHODS: Patients who received LZD 600 mg twice daily at Hokkaido University Hospital from September 2008 to April 2019 were enrolled in this retrospective observational study. Patient characteristics, concomitant medications, laboratory data, and the occurrence of vomiting were obtained from electronic medical records. Logistic regression analysis was performed to identify risk factors for vomiting, including age, sex, body weight, concomitant medications, and surgeries. RESULTS: A total of 496 patients were included in this study, of which 90 experienced vomiting. By multivariate logistic regression analysis, female sex (adjusted odds ratio [aOR], 2.69; 95% confidence interval [CI], 1.62-4.47), ≥ 10 days of LZD administration (aOR, 2.57; CI, 1.46-4.50), and hyponatraemia (aOR, 2.96; CI, 1.72-5.10) were identified as independent risk factors for vomiting; administration of serotonergic agents (aOR, 0.23; CI, 0.07-0.82) was negatively associated. CONCLUSIONS: This study is the first to successfully identify risk factors for LZD-induced vomiting. Careful monitoring of patients with these risk factors may lead to safer and sustainable LZD administration.

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 7,306 patients that were enrolled, VIN occurred in 14.2% of them (1,035). 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.