PK/PD指导MRSA肺部感染伴低蛋白血症患者使用替考拉宁的临床研究Clinical Study in Patients with Pulmonary Infection with MRSA and Hypoproteinemia Using Teicolanin based on PK/PD Theory
贾号;
JIA Hao;First People's Hospital of Shangqiu;
摘要(Abstract):
目的探讨耐甲氧西林金黄色葡萄球菌(MRSA)肺部感染伴低蛋白血症患者使用替考拉宁时,对替考拉宁血药浓度、药动学参数和临床疗效的影响。方法选取2018年1~12月我院重症监护病房收治的44例MRSA肺部感染伴低蛋白血症(白蛋白<25 g·L(-1))患者,将其分为两组,A组(14例)给予替考拉宁起始6 mg·kg(-1))患者,将其分为两组,A组(14例)给予替考拉宁起始6 mg·kg(-1)q12h×3次维持6 mg·kg(-1)q12h×3次维持6 mg·kg(-1)qd治疗,B组(14例)给予起始12 mg·kg(-1)qd治疗,B组(14例)给予起始12 mg·kg(-1)q12h×3次维持12 mg·kg(-1)q12h×3次维持12 mg·kg(-1)qd治疗,蛋白水平正常者为对照组(16例),给予起始6 mg·kg(-1)qd治疗,蛋白水平正常者为对照组(16例),给予起始6 mg·kg(-1)q12h×3次维持6 mg·kg(-1)q12h×3次维持6 mg·kg(-1)qd治疗。分析比较3组患者治疗后的血药浓度、AUC_(0-24)/MIC和临床疗效。结果第6剂给药前30 min,A组替考拉宁血浓度显著低于对照组(P<0.01)、B组替考拉宁的血药浓度与对照组无统计学差异。A组患者的AUC_(0-24)/MIC及AUC_(0-24)/MIC≥345(%)显著低于对照组(P<0.01),而B组与对照组均无统计学差异。A组、B组替考拉宁的CL和Vd均显著高于对照组(P<0.01)。A组疗效低于对照组(P<0.05),B组与对照组差异无统计学意义(P>0.05)。结论低蛋白血症会降低替考拉宁的血药浓度、AUC_(0-24)/MIC,降低临床疗效,并且低蛋白血症患者的肌酐清除率和表观分布容积显著增加。通过提高剂量,可提高替考拉宁的血药浓度、AUC_(0-24)/MIC,增加临床疗效。
OBJECTIVE To investigate the effects of teicoplanin on blood concentration,pharmacokinetic parameters and clinical efficacy in patients with meticillin-resistant Staphylococcus aureus(MRSA) pulmonary infection and hypoproteinemia. METHODS 44 patients with lung infection with MRSA and hypoalbuminemia in ICU from Jan.2018 to Dec.,2018 were divided into two groups. Group A was gave 6 mg·kg(-1)qd治疗。分析比较3组患者治疗后的血药浓度、AUC_(0-24)/MIC和临床疗效。结果第6剂给药前30 min,A组替考拉宁血浓度显著低于对照组(P<0.01)、B组替考拉宁的血药浓度与对照组无统计学差异。A组患者的AUC_(0-24)/MIC及AUC_(0-24)/MIC≥345(%)显著低于对照组(P<0.01),而B组与对照组均无统计学差异。A组、B组替考拉宁的CL和Vd均显著高于对照组(P<0.01)。A组疗效低于对照组(P<0.05),B组与对照组差异无统计学意义(P>0.05)。结论低蛋白血症会降低替考拉宁的血药浓度、AUC_(0-24)/MIC,降低临床疗效,并且低蛋白血症患者的肌酐清除率和表观分布容积显著增加。通过提高剂量,可提高替考拉宁的血药浓度、AUC_(0-24)/MIC,增加临床疗效。
OBJECTIVE To investigate the effects of teicoplanin on blood concentration,pharmacokinetic parameters and clinical efficacy in patients with meticillin-resistant Staphylococcus aureus(MRSA) pulmonary infection and hypoproteinemia. METHODS 44 patients with lung infection with MRSA and hypoalbuminemia in ICU from Jan.2018 to Dec.,2018 were divided into two groups. Group A was gave 6 mg·kg(-1)12-hourly intravenously for 3 times followed by 6 mg·kg(-1)12-hourly intravenously for 3 times followed by 6 mg·kg(-1) once daily,group B was gave 12 mg·kg(-1) once daily,group B was gave 12 mg·kg(-1)12-hourly intravenously for 3 times followed by 12 mg·kg(-1)12-hourly intravenously for 3 times followed by 12 mg·kg(-1) once daily,the control group with normal protein levels,was gave 6 mg·kg(-1) once daily,the control group with normal protein levels,was gave 6 mg·kg(-1)12-hourly intravenously for 3 times followed by 6 mg·kg(-1)12-hourly intravenously for 3 times followed by 6 mg·kg(-1) once daily. After treatment,the serum drug concentration,AUC_(0-24)/MIC and clinical efficacy of the three groups were analyzed and compared. RESULTS Before 30 min,the 6 th dose was administered,the blood concentration of teicoplanin,AUC_(0-24)/MIC,and AUC_(0-24)/MIC ≥125(%) in group A were significantly lower than that in the control group(P<0.01),while there was no statistical difference between group B and the control group. The CL and Vd of group A and group B were significantly higher than that of the control group(P<0.01). Compared with the control group,the clinical efficacy of group A was significantly reduced,while there was no statistical difference between group B and the control group. CONCLUSION Hypoproteinemia can reduce the blood drug concentration and AUC_(0-24)/MIC of teicolanine,and the clinical efficacy,and significantly increase the creatinine clearance rate and apparent volume of distribution in patients with hypoproteinemia. By increasing the dose,the blood concentration and AUC_(0-24)/MIC and the clinical efficacy of teicolanin can be increased.
关键词(KeyWords):
替考拉宁;耐甲氧西林金黄色葡萄球菌;低蛋白血症;血药浓度
teicoplanin;methicillin-resistant Staphylococcus aureus;hypoproteinemia;blood drug concentration
基金项目(Foundation):
作者(Authors):
贾号;
JIA Hao;First People's Hospital of Shangqiu;
参考文献(References):
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