80岁以上高龄重症患者使用万古霉素的安全性分析

Safety of vancomycin in over-80-year-old patients with severe Gram-positive infections

目的：观察万古霉素治疗革兰阳性菌感染的高龄重症患者有效性及其对肾功能的影响。方法回顾性地分析2007年1月至2014年3月期间南京医科大学第一附属医院老年重症监护室收治的≥80岁革兰阳性菌感染的老年患者48例，静脉应用万古霉素，观察患者症状及体征变化，进行病原体分析，评价其临床疗效并动态观察用药期间肾功能变化。结果48例患者使用万古霉素治疗平均疗程为（18±9）d ，临床有效率为72.92%，其中明确培养或涂片有革兰阳性球菌者39例，共培养出菌株50株，经治疗后细菌清除率为82.25%。万古霉素治疗过程中出现肾毒性12例（25%），单因素 logistic 回归分析显示，治疗前急性生理与慢性健康评分（APACHE Ⅱ）（OR＝1.240，95% CI：1.061～1.449，P＝0.007）、平均万古霉素谷浓度（OR＝1.268，95% CI：1.066～1.757，P＝0.014）、合并使用升压药[（将其分为3层：未用升压药；小剂量升压药；大剂量升压药），（OR＝4.335，95%CI：1.620～11.598，P＝0.003）]、合并使用利尿剂[（将其按照呋塞米日剂量分为4层：≤40mg/d、41～80mg/d、81～120mg/d、＞120mg/d），（OR＝2.066，95%CI：1.189～3.589，P＝0.010）]为本组高龄患者万古霉素用药后出现肾毒性的危险因素。多因素 logistic 回归分析显示，APACHE Ⅱ评分≥25分、平均万古霉素谷浓度≥18mg/L、合并利尿剂（呋塞米≥40mg/d）均会增加高龄患者的肾毒性风险。结论万古霉素用于高龄重症患者革兰阳性球菌感染的治疗是有效的。高龄重症患者使用万古霉素具有一定的肾毒性风险，其独立危险因素为治疗前 APACHE Ⅱ评分≥25分、万古霉素谷浓度≥18mg/L 及呋塞米用量≥40mg/d。

Objective To investigate the efficacy of vancomycin in the treatment of severe Gram-positive infections in very old patients and determine its effect on renal functions. Methods A total of 48 very old patients （age ≥80 years） with confirmed Gram-positive infection admitted in our geriatric unit from January 2007 to March 2014 were included in this study. They all received venous injection of vancomycin. Pathogen analysis was conducted for all the patients. Their signs and symptoms were observed before and after the treatment, as well as the clinical efficiency. And renal functions were evaluated dynamically during the treatment. Results The course of vancomycin treatment was averagely （18±9）d for the 48 patients, and the clinical efficiency was 72.92%. Among the 48 patients, 39 were infected by Gram-positive cocci in the bacterial culture or in smear test, and a total of 50 isolated strains were obtained. The bacterial clearance rate reached 82.25% after the vancomycin therapy. During the vancomycin treatment, 12 cases had renal toxicity, accounting for 25% of the total cases. Univariate logistic analysis showed that pre-treatment score of Acute Physiology And Chronic Health Evaluation （APACHE） Ⅱ（OR=1.240, 95% CI： 1.061-1.449, P=0.007）, mean trough concentration of vancomycin （OR=1.268, 95% CI： 1.066-1.757, P=0.014）, the combined use of vasopressor agent （stratified into 3 groups, receiving no, small and large doses; OR=4.33, 95% CI： 1.620-11.598, P=0.0035）, and the combined use of diuretics （stratified into 4 groups according to daily dose of furosemide, that is, ≤40, 41-80, 81-120 and 〉120mg/d; OR=2.066, 95% CI： 1.189-3.589, P=0.010） were risk factors for renal toxicity in the cohort during vancomycin treatment. Multivariate logistic regression analysis demonstrated that APACHE Ⅱscore ≥25 points, trough concentrations of vancomycin ≥18mg/L, and the combined use of diuretics （furosemide ≥40mg/d） would increase the risks of renal toxicity in the elderly patients. Conclusion Vancomycin is efficient in the treatment of severe Gram-positive infections in the elderly patients. But for them, the treatment leads to certain risk for renal toxicity, and the pre-treatment APACHE Ⅱ score ≥25 points, trough concentrations of vancomycin ≥18mg/L, and combined use of diuretics （furosemide ≥40mg/d） are independent risk factors for the toxicity.