血流感染老年患者万古霉素血药谷浓度与急性肾损伤的相关性
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摘要
目的分析重症医学科(ICU)老年患者耐甲氧西林金黄色葡萄球菌(MRSA)血流感染治疗药物万古霉素的血药浓度监测(TDM)与急性肾损伤(AKI)的关系,为临床合理用药提供参考。方法遴选2016年7月—2017年5月符合标准的ICU老年患者48例,参考药品说明书老年人推荐剂量给予万古霉素1 g·d-1,分2次给药,5个半衰期后,即血药浓度达稳态后,采用液相色谱法测定万古霉素稳态谷、峰浓度。根据AKI诊断标准分为AKI组和非AKI组。临床药师根据TDM结果,结合患者个体病程,辅助调整临床用药。最后分别比较治疗5个半衰期后、7 d后两组之间万古霉素平均谷浓度、峰浓度差异。结果万古霉素血药浓度达到稳态后,稳态谷浓度、峰浓度在治疗窗范围内的患者仅占36.46%,谷浓度低于治疗窗范围占43. 75%。发生AKI 27例(56. 25%),未发生AKI 21例(43. 75%)。谷浓度5～10 mg·L~(-1),>10～20 mg·L~(-1),>20 mg·L~(-1)患者发生AKI的概率分别为23.81%,77.78%,88.89%。不同谷浓度范围发生AKI概率差异有统计学意义。根据万古霉素TDM结果调整剂量治疗7 d后,发生AKI 35例(72.92%),未发生AKI13例(27.08%)。治疗5个半衰期后,两组万古霉素平均谷浓度差异有统计学意义;治疗7 d后两组万古霉素平均谷浓度差异无统计学意义。结论危重症老年患者具有特殊的病理生理状态,使用万古霉素治疗个体差异大,应加强TDM监测。AKI发生因素除了万古霉素血药浓度外,还与患者的年龄、基础疾病、感染严重程度等因素有关。
Objective By analyzing of the correlation between plasma concentration and acute renal injury of the vancomycin in elderly patients with methicillin-resistant staphylococcus aureus( MRSA) bloodstream infection in intensive care unit( ICU). Methods By selecting 48 cases of ICU elderly patients who met the criteria from July 2016 to May 2017,the vancomycin twice a day with a dose of 1 g·d-1 were given according to the drug instructions for the elderly patients. Then a HPLC method was established for the determination of the serum trough and peak concentration of vancomycin after 5 half-lives( 5 t1/2).The cases were divided into two groups of AKI and non-AKI according to the diagnostic criteria for acute kidney injury( AKI).After that,the clinical pharmacists could help to adjust the clinical medication regimen according to the results of TDM monitoring and the patients' individual courses. At last,the differences of the average trough and the average peak concentration of vancomycin concentration after 5 t1/2 and 7 days between the two groups were compared. Results After 5 t1/2 of vancomycin,the trough and peak concentration of vancomycin in the treatment window were only 36.46% and the trough concentration lower than the treatment window were 43. 75%. Among the 48 cases,27 cases( 56. 25%) caught the AKI while the other 21 cases( 43.75%) didn't. The rate of occurrence of AKI was 23.81%,77.78% and 88.89%,respectively,in the patients with the trough concentration of 5-10 mg·L~(-1),>10-20 mg·L~(-1) and >20 mg·L~(-1). There were significant differences in the probability of catching a AKI between different trough concentrations. Among the 48 cases,35 cases( 72. 92%) caught the AKI while the other 13 cases( 27.08%) didn't after the dosage adjustment for 7 days according to the results of vancomycin TDM monitoring.Compared with the trough concentration between the two groups, the difference was statistically significant after 5 t1/2 of vancomycin while had no statistical significance after 7 days. Conclusion The elderly patients with critical diseases have special pathophysiological status. When using the vancomycin,they should be strengthened the TDM monitoring because the effective concentrations of the drugs varied in different patients. In addition to considering the concentration of vancomycin,the age、underlying diseases and the severity of the infection should be taken into consideration.
Objective By analyzing of the correlation between plasma concentration and acute renal injury of the vancomycin in elderly patients with methicillin-resistant staphylococcus aureus( MRSA) bloodstream infection in intensive care unit( ICU). Methods By selecting 48 cases of ICU elderly patients who met the criteria from July 2016 to May 2017,the vancomycin twice a day with a dose of 1 g·d-1 were given according to the drug instructions for the elderly patients. Then a HPLC method was established for the determination of the serum trough and peak concentration of vancomycin after 5 half-lives( 5 t1/2).The cases were divided into two groups of AKI and non-AKI according to the diagnostic criteria for acute kidney injury( AKI).After that,the clinical pharmacists could help to adjust the clinical medication regimen according to the results of TDM monitoring and the patients' individual courses. At last,the differences of the average trough and the average peak concentration of vancomycin concentration after 5 t1/2 and 7 days between the two groups were compared. Results After 5 t1/2 of vancomycin,the trough and peak concentration of vancomycin in the treatment window were only 36.46% and the trough concentration lower than the treatment window were 43. 75%. Among the 48 cases,27 cases( 56. 25%) caught the AKI while the other 21 cases( 43.75%) didn't. The rate of occurrence of AKI was 23.81%,77.78% and 88.89%,respectively,in the patients with the trough concentration of 5-10 mg·L~(-1),>10-20 mg·L~(-1) and >20 mg·L~(-1). There were significant differences in the probability of catching a AKI between different trough concentrations. Among the 48 cases,35 cases( 72. 92%) caught the AKI while the other 13 cases( 27.08%) didn't after the dosage adjustment for 7 days according to the results of vancomycin TDM monitoring.Compared with the trough concentration between the two groups, the difference was statistically significant after 5 t1/2 of vancomycin while had no statistical significance after 7 days. Conclusion The elderly patients with critical diseases have special pathophysiological status. When using the vancomycin,they should be strengthened the TDM monitoring because the effective concentrations of the drugs varied in different patients. In addition to considering the concentration of vancomycin,the age、underlying diseases and the severity of the infection should be taken into consideration.
引文
[1]肖永红.美国感染病协会耐甲氧西林金黄色葡萄球菌感染治疗指南要点[J].中国医学前沿杂志,2011,2(3):53-56.
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[4] RONCO C,LEVIN A,WAMOCK D G,et al. Improving outcomes from acute kidney injury(AKI):report on an initiative[J].Int J Artif Organs,2007,30(5):373-376.
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[6]黄珊,林玮玮,王长连,等.基于决策树的万古霉素血药浓度解读及实践[J].中国药学杂志,2016,19(51):1710-1713.
[7]刘素琴,沈国琴,朱洁,等.146例万古霉素临床应用分析[J].医药导报,2016,35(增):123-124.
[8] HE X R,LU W,ZOU D,et al.Advance on population pharmacokinetic models of vancomycin[J]. Chin Pharm J,2013,48(2):2075-2080.
[9] PEA F,VIALE P,FURLANUT M.Antimicrobial therapy in criticallyill patients:a review of pathophysiological conditions responsible for altered disposition and pharmacokinetic variability[J]. Clin Pharmacokinet,2005,44(10):1009-1034.
[10] MARIA DEL MAR FERNANDEZ DE GATTA GARCIA M,REVILLA N,CALVO M V,et al. Pharmacokinetic/pharmacodynamic analysis of vancomycin in ICU patients[J].Intensive Care Med,2007,33(2):279-285.
[11] HU J L,ZHANG J.Research up dates of vancomycin nephrotoxicity[J].Chin J Infect Chemother,2013,13(5):394-399.
[12] RYBAK M J,LOMAESTRO B M,ROTSCHAFER J C, et al. Vancomycin therapeutic guidelines:a summary of consensus recommendations from the infectious diseases Society of America,the American Society of Health-System Pharmacists,and the Society of Infectious Diseases Pharmacists[J].Clin Infect Dis,2009,49(3):325-327.
[13]姜慧婷,何娟,杨婉花.危重症患者万古霉素给药方案调整的研究进展[J].世界临床药物,2014,35(7):439-442.
[2] SANFORD J P.美国桑福德抗微生物治疗指南[M].44版.北京:中国协和医科大学出版社,2014:65.
[3] LIU C,BAYER A,COSGROVE S E.Clinical practiceguidelines by the infectious diseases society of america for thetreatment of methicillin-resistant Staphylococcus aureus infections in adults and children[J].Clin Infect Dis,2011,52(3):e18-55.
[4] RONCO C,LEVIN A,WAMOCK D G,et al. Improving outcomes from acute kidney injury(AKI):report on an initiative[J].Int J Artif Organs,2007,30(5):373-376.
[5] YE Z K,LI X G,ZHAI S D.Therapeutic drug monitoring of vancomycininchian:current status andevaluation[J]. Chin J Clin Pharmacol,2013,29(7):545-548.
[6]黄珊,林玮玮,王长连,等.基于决策树的万古霉素血药浓度解读及实践[J].中国药学杂志,2016,19(51):1710-1713.
[7]刘素琴,沈国琴,朱洁,等.146例万古霉素临床应用分析[J].医药导报,2016,35(增):123-124.
[8] HE X R,LU W,ZOU D,et al.Advance on population pharmacokinetic models of vancomycin[J]. Chin Pharm J,2013,48(2):2075-2080.
[9] PEA F,VIALE P,FURLANUT M.Antimicrobial therapy in criticallyill patients:a review of pathophysiological conditions responsible for altered disposition and pharmacokinetic variability[J]. Clin Pharmacokinet,2005,44(10):1009-1034.
[10] MARIA DEL MAR FERNANDEZ DE GATTA GARCIA M,REVILLA N,CALVO M V,et al. Pharmacokinetic/pharmacodynamic analysis of vancomycin in ICU patients[J].Intensive Care Med,2007,33(2):279-285.
[11] HU J L,ZHANG J.Research up dates of vancomycin nephrotoxicity[J].Chin J Infect Chemother,2013,13(5):394-399.
[12] RYBAK M J,LOMAESTRO B M,ROTSCHAFER J C, et al. Vancomycin therapeutic guidelines:a summary of consensus recommendations from the infectious diseases Society of America,the American Society of Health-System Pharmacists,and the Society of Infectious Diseases Pharmacists[J].Clin Infect Dis,2009,49(3):325-327.
[13]姜慧婷,何娟,杨婉花.危重症患者万古霉素给药方案调整的研究进展[J].世界临床药物,2014,35(7):439-442.