Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA
Department of Biomedical Sciences, College of Graduate Studies, Midwestern University, Downers Grove, Illinois, USA.
Antimicrob Agents Chemother. 2019 Sep 23;63(10). doi: 10.1128/AAC.00761-19. Print 2019 Oct.
Previous literature suggests that maternal vancomycin crosses the placental barrier to the fetus. Further, early animal studies indicated that kidney injury was not observed in the progeny. These studies were conducted prior to the availability of sensitive biomarkers for kidney injury. Therefore, a previous finding of no renal damage to the infant may be misleading. Vancomycin was administered intravenously to pregnant rats at a dose of 250 mg/kg of body weight/day ( = 6 per trimester) on three consecutive gestational days (GD) during trimesters 1, 2, and 3 (T1, T2, and T3, respectively) in three independent cohorts. The dams carried to term and delivered vaginally on GD 21. Kidneys were harvested from dams and pups and homogenized. Samples were prepared by protein precipitation and injected in a liquid chromatography tandem mass spectrometer, and vancomycin was quantified. The kidney tissue homogenate from dams and pups were analyzed for kidney injury molecule-1 (KIM-1). As trimesters progressed, the quantity of vancomycin increased linearly in the kidneys of both rat dams and pups ( < 0.0001 for T1 and T3, < 0.0001 for T2 and T3, and < 0.0001 for T3 and T3 control for both rat dams and pups). KIM-1 concentrations in pup kidneys were significantly higher when dams were administered vancomycin in trimesters 1 ( = 0.0001) and 2 ( = 0.0024) than in controls in trimester 3. Data demonstrate persistence of vancomycin in maternal and rat pup kidneys in all three trimesters of pregnancy with associated damage to the kidney, as indicated by expression of KIM-1.
先前的文献表明，母体万古霉素可穿过胎盘屏障进入胎儿体内。此外，早期的动物研究表明，在后代中未观察到肾损伤。这些研究是在肾损伤的敏感生物标志物可用之前进行的。因此，以前关于婴儿肾脏无损伤的发现可能具有误导性。在三个独立的队列中，将 250mg/kg 体重/天（每个孕期 6 只）的万古霉素静脉注射给怀孕的大鼠，连续三天（GD），在孕期第 1、2 和 3 天（分别为 T1、T2 和 T3）进行。母鼠在 GD21 时经阴道分娩。从母鼠和幼鼠中取出肾脏并匀浆。通过蛋白沉淀制备样品，并在液相色谱串联质谱仪中进行注射，定量万古霉素。分析母鼠和幼鼠肾脏组织匀浆的肾损伤分子-1（KIM-1）。随着孕期的进展，母鼠和幼鼠肾脏中的万古霉素含量呈线性增加（T1 和 T3 时均 < 0.0001，T2 和 T3 时均 < 0.0001，T3 和 T3 对照组时均 < 0.0001）。当在孕期 1 期（ = 0.0001）和 2 期（ = 0.0024）给予母鼠万古霉素时，幼鼠肾脏中的 KIM-1 浓度明显高于对照组在孕期 3 期。数据表明，万古霉素在母体和大鼠幼鼠肾脏中在整个孕期的三个孕期均持续存在，并通过 KIM-1 的表达表明肾脏受损。
