重症肺部感染患者肺泡上皮衬液万古霉素渗透性研究

目的对万古霉素在重症肺炎患者的肺组织渗透性进行探索,了解万古霉素在肺组织内分布情况,为研究万古霉素组织浓度与疗效相关性,制订更精准药物治疗方案提供参考。方法选取2016年5月—2017年1月间入住老年重症监护病房(ICU)、因肺部感染使用万古霉素,呼吸衰竭进行机械通气且治疗期间需进行支气管肺泡灌洗治疗患者。万古霉素0.5 g,q8h,持续静脉输注1 h。分别于用药3 d后,于给药间隔内进行一次支气管肺泡灌洗,收集灌洗液和同时期的血液样本,利用液相色谱-串联质谱(LC-MS/MS)法测定万古霉素浓度。同时使用尿素试剂盒对二者中尿素浓度进行测定,以获得灌洗液中药物浓度的稀释倍数,利用Renard公式计算药物在肺组织的渗透性,以渗透率表示。结果纳入符合条件的患者16例,其中男12例,女4例。平均年龄60.94岁,平均急性生理及慢性健康(APACHEⅡ)评分30.31分,主要诊断均为肺部感染,住院期间死亡2例,主要死亡原因为多器官功能衰竭。用药后感染性指标中白细胞(WBC)计数和降钙素原(PCT)差异有统计学意义(P<0.05)。肺泡灌洗操作平均分布在给药间隔内5个采血点,灌洗液回收率为38.83%,尿素在灌洗液中稀释倍数平均为37.34倍(17.8~79倍),肺泡上皮衬液中药物浓度为1.48~10.15μg·mL^-1,万古霉素血清药物浓度为8.71~61.96μg·mL^-1,万古霉素在肺组织渗透率为23.12%。结论万古霉素对重症患者肺部渗透性较低,在血药浓度达标的情况下,感染部位抗菌药物的实际浓度可能并不能达到最佳靶值,可能导致治疗失败。

Effect of Permeability of Vancomycin into the Alveolar Epithelial Lining Fluid in Patients with Severe Pulmonary Infection

Objective To explore the permeability of vancomycin into epithelial lining fluid(ELF)of patients with severe pneumonia,and to understand the distribution of vancomycin in lung tissue.The study is to provide references for studying the correlation between vancomycin tissue concentration and therapeutic effect and formulating more accurate drug treatment plan.Methods Patients admitted to ICU from May 2016 to January 2017,who needed vancomycin for pulmonary infection,mechanical ventilation for respiratory failure and bronchoalveolar lavage therapy during treatment,were selected.Vancomycin was given 0.5 g,q8h for continuously intravenous infusion for 1 h.Bronchoalveolar lavage was performed 3 days after the administration,and lavage fluid and blood samples from the same period were collected.Vancomycin concentration was determined by LC-MS/MS.The apparent volume of ELF recovered by bronchoalveolar lavage was determined by using urea as an endogenous marker.The permeability of the drug in the lung tissue was calculated by Renard formula,expressed as the ratio of ELF/plasma.Results Sixteen patients were included,including 12 males(75%)and 4 females(25%).The average age was 60.94 years old,and the average APACHE II score was 30.31.The main diagnosis was pulmonary infection,and the mortality rate during hospitalization was 12.5%with the main cause of death of multi-organ failure.White blood cell(WBC)count and procalcitonin(PCT)were statistically different before and after the treatment(P<0.05).The recovery rate of lavage fluid was 38.83%,and the dilution rate of urea in lavage fluid was 37.34 times(17.8-79 times)to average.Vancomycin levels in ELF ranged from 1.48 to 10.15μg·mL^-1,while the mean simultaneous level of the drug in serum was from 8.71 to 61.96μg·mL^-1.The ratio ELF/plasma of drug penetration was 23.12%.Conclusion Vancomycin has a low pulmonary permeability in critically ill patients.When the concentration of vancomycin reaches the standard,the actual concentration in ELF may not reach the optimal target value,which may lead to treatment failure.