Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile
Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile
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DOI：
10.1111/tid.12588
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发表时间：
2016-10-01
影响因子：
2.6
通讯作者：
Hanigan, S. M.
中科院分区：
文献类型：
--
作者：
Early, C. R.;Park, J. M.;Hanigan, S. M.
背景两个病例报告表明，甲硝唑治疗艰难梭菌感染（CDI）增加了他克莫司（TAC）的谷浓度。本研究的主要目的是确定这种潜在相互作用在接受CDI治疗的移植患者中的临床意义。目前，没有强大的文献存在，以估计甲硝唑和TAC.MethodsIn这项回顾性研究，CDI和甲硝唑治疗对TAC水平的影响，在52名成人实体器官移植患者的药代动力学相互作用的幅度进行了调查。主要结果是确定甲硝唑或万古霉素治疗患者的基线和症状缓解之间的剂量标准化TAC水平差异。次要结果是确定在基线和CDI diagnosis.ResultsThe对数转换的剂量标准化TAC水平从基线到症状解决的平均变化为0.99甲硝唑（n = 35）和1.04万古霉素（n = 17）治疗的差异。两组之间的平均差异为0.96（95%置信区间：0.74-1.24）。剂量标准化TAC水平在CDI诊断和基线之间无显着差异（P = 0.37）。结论与万古霉素相比，用甲硝唑治疗CDI与TAC水平增加>30%无关。两个治疗组都需要调整TAC剂量以维持目标TAC水平，而甲硝唑治疗组不需要显著更大的剂量调整。
BackgroundTwo case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC.MethodsIn this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis.ResultsThe average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n = 35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37).ConclusionCDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment.