{"title":"万古霉素联合哌西林-他唑巴坦与急性肾损伤的关系:区分假损伤与真肾毒性","authors":"Congqin Chen, Rijing Zhou, Jie Fang, Jie Xiao","doi":"10.1111/cts.70258","DOIUrl":null,"url":null,"abstract":"<p>The combination of vancomycin and piperacillin-tazobactam (VPT) is widely used for severe infections, but its potential synergistic nephrotoxicity remains debated. This study used the FDA Adverse Event Reporting System (FAERS) database via AERSMine to assess the risk of AKI with VPT and vancomycin plus carbapenems (VC), compared to other vancomycin-based regimens to evaluate the hypothesis of <i>pseudo</i>-nephrotoxicity versus true nephrotoxicity. Disproportionality analysis was performed using the reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN). Model 1 included all vancomycin-associated reports, while Model 2 focused on reports from healthcare professionals. In Model 1, a safety signal was detected for overall AKI (ROR: 1.31, 95% CI: 1.26–1.37; IC025: 0.21) and changes in creatinine (ROR: 1.23, 95% CI: 1.10–1.38; IC025: 0.12) with VPT. In contrast, no significant disproportionality signal was observed for changes in other biomarkers (ROR: 0.89, 95% CI: 0.70–1.14; IC025: −0.38), severe AKI (ROR: 0.82, 95% CI: 0.76–0.89; IC025: −0.31), or renal replacement therapy (RRT) initiation (ROR: 1.08, 95% CI: 0.90–1.29; IC025: −0.09). No safety signal of increased risk of AKI was detected for VC versus other vancomycin-containing regimens across all subgroups. Model 2 confirmed this trend. These findings suggest that creatinine-defined AKI with VPT may represent pseudotoxicity rather than true nephrotoxicity. Further research is needed to clarify the safety profile of VPT.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 5","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70258","citationCount":"0","resultStr":"{\"title\":\"Association of Vancomycin Plus Piperacillin-Tazobactam With Acute Kidney Injury: Differentiating Pseudo-Injury From True Nephrotoxicity\",\"authors\":\"Congqin Chen, Rijing Zhou, Jie Fang, Jie Xiao\",\"doi\":\"10.1111/cts.70258\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The combination of vancomycin and piperacillin-tazobactam (VPT) is widely used for severe infections, but its potential synergistic nephrotoxicity remains debated. This study used the FDA Adverse Event Reporting System (FAERS) database via AERSMine to assess the risk of AKI with VPT and vancomycin plus carbapenems (VC), compared to other vancomycin-based regimens to evaluate the hypothesis of <i>pseudo</i>-nephrotoxicity versus true nephrotoxicity. Disproportionality analysis was performed using the reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN). Model 1 included all vancomycin-associated reports, while Model 2 focused on reports from healthcare professionals. In Model 1, a safety signal was detected for overall AKI (ROR: 1.31, 95% CI: 1.26–1.37; IC025: 0.21) and changes in creatinine (ROR: 1.23, 95% CI: 1.10–1.38; IC025: 0.12) with VPT. In contrast, no significant disproportionality signal was observed for changes in other biomarkers (ROR: 0.89, 95% CI: 0.70–1.14; IC025: −0.38), severe AKI (ROR: 0.82, 95% CI: 0.76–0.89; IC025: −0.31), or renal replacement therapy (RRT) initiation (ROR: 1.08, 95% CI: 0.90–1.29; IC025: −0.09). No safety signal of increased risk of AKI was detected for VC versus other vancomycin-containing regimens across all subgroups. Model 2 confirmed this trend. These findings suggest that creatinine-defined AKI with VPT may represent pseudotoxicity rather than true nephrotoxicity. Further research is needed to clarify the safety profile of VPT.</p>\",\"PeriodicalId\":50610,\"journal\":{\"name\":\"Cts-Clinical and Translational Science\",\"volume\":\"18 5\",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-05-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70258\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cts-Clinical and Translational Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cts.70258\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cts-Clinical and Translational Science","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cts.70258","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Association of Vancomycin Plus Piperacillin-Tazobactam With Acute Kidney Injury: Differentiating Pseudo-Injury From True Nephrotoxicity
The combination of vancomycin and piperacillin-tazobactam (VPT) is widely used for severe infections, but its potential synergistic nephrotoxicity remains debated. This study used the FDA Adverse Event Reporting System (FAERS) database via AERSMine to assess the risk of AKI with VPT and vancomycin plus carbapenems (VC), compared to other vancomycin-based regimens to evaluate the hypothesis of pseudo-nephrotoxicity versus true nephrotoxicity. Disproportionality analysis was performed using the reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN). Model 1 included all vancomycin-associated reports, while Model 2 focused on reports from healthcare professionals. In Model 1, a safety signal was detected for overall AKI (ROR: 1.31, 95% CI: 1.26–1.37; IC025: 0.21) and changes in creatinine (ROR: 1.23, 95% CI: 1.10–1.38; IC025: 0.12) with VPT. In contrast, no significant disproportionality signal was observed for changes in other biomarkers (ROR: 0.89, 95% CI: 0.70–1.14; IC025: −0.38), severe AKI (ROR: 0.82, 95% CI: 0.76–0.89; IC025: −0.31), or renal replacement therapy (RRT) initiation (ROR: 1.08, 95% CI: 0.90–1.29; IC025: −0.09). No safety signal of increased risk of AKI was detected for VC versus other vancomycin-containing regimens across all subgroups. Model 2 confirmed this trend. These findings suggest that creatinine-defined AKI with VPT may represent pseudotoxicity rather than true nephrotoxicity. Further research is needed to clarify the safety profile of VPT.
期刊介绍:
Clinical and Translational Science (CTS), an official journal of the American Society for Clinical Pharmacology and Therapeutics, highlights original translational medicine research that helps bridge laboratory discoveries with the diagnosis and treatment of human disease. Translational medicine is a multi-faceted discipline with a focus on translational therapeutics. In a broad sense, translational medicine bridges across the discovery, development, regulation, and utilization spectrum. Research may appear as Full Articles, Brief Reports, Commentaries, Phase Forwards (clinical trials), Reviews, or Tutorials. CTS also includes invited didactic content that covers the connections between clinical pharmacology and translational medicine. Best-in-class methodologies and best practices are also welcomed as Tutorials. These additional features provide context for research articles and facilitate understanding for a wide array of individuals interested in clinical and translational science. CTS welcomes high quality, scientifically sound, original manuscripts focused on clinical pharmacology and translational science, including animal, in vitro, in silico, and clinical studies supporting the breadth of drug discovery, development, regulation and clinical use of both traditional drugs and innovative modalities.