ICU抗菌药物用药剂量不足风险研讨新

1、ICU抗菌药物用药剂量不足风险研讨新 VPA 1.2g/d，3d后，VPA 39.91 更改至1.6g/d，7d后，VPA 19.32 （ VAP 达标 浓度 50-100） VAN 1.0g，q12h，2d后，VAN 2.37 （VAN 达标浓度10，甚至更高）临床常用的给药剂量 哌拉西林他唑巴坦哌拉西林他唑巴坦 （4.5g/支）支）临床常用的给药剂量 美罗培南（美罗培南（0.5g/支）支） However, when a subject is exposed to a standard dose of an antibacterial in daily practice, the pK/p

2、D ratio achieved may be lower than expected as a consequence of the patients clinical condition and the characteristics of the involved pathogen This may be considered as underdosing, the result of which will be a therapeutic failure. In critically ill patients, there are a number of reasons for an

3、inadequate pK/pD ratio of antimicrobials at the site of infection and that should be considered in case of poor clinical outcome or therapeutic failure (table III).1. 给药剂量不足按照实际体重计算用药剂量 （actual bodyweight）氨基糖苷类、糖肽类、两性霉素氨基糖苷类、糖肽类、两性霉素B、达托霉素、达托霉素按照标准体重估算给药剂量 （standardized bodyweight）内酰胺类、替加环素、棘白菌素、大环内

4、脂、喹诺酮类内酰胺类、替加环素、棘白菌素、大环内脂、喹诺酮类宜进行剂量调整人群包括宜进行剂量调整人群包括1.Overweight2.亲脂性药物 actual bodyweight3.亲水性药物 ideal bodyweight2.感染局部浓度不足感染局部浓度不足原因分析原因分析1.血供减少2.细胞膜通过/进入障碍3.分布容积增加/胶体渗透压减低4.蛋白结合率高的药物分布障碍5.屏障作用（CNS）3.清除率增加清除率增加美罗培南比阿培南美罗培南比阿培南With dialysis, without previous liver transplantation/resection,with dial

5、ysis, with previous liver transplantation/resectionwithout dialysis,without previous liver transplantation/resectionwithout dialysis, with previous liver transplantation/resectionConclusion Dialysis increased the CI of linezolid by 3.5 L/h, corresponding to a mean increase of 23%. In patients after

6、liver transplantation/resection, linezolid CI was reduced by 60% relative to patients without prior liver transplantation/resection.No correlation could be established between anidulafungin exposureand disease severity or plasma protein concentrations inthis group of critically ill patients. In this

7、 population, we observed a lower anidulafungin exposure than in the general patient population.In patients infected with a susceptible Candida albicans orglabrata strain with a MIC well below the breakpoint, no problemsare to be expected in the case of a lower exposure. However, in patients with less-susceptible Candida albicans or glabrata strains,a lower exposure can be a problem. If theMICis high