Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: Lessons from the DALI Study

The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10–30 mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2–26.0) and free 1.5 (0.7–2.5); trough, total 11.9 (10.2–22.7) and free 1.8 (0.6–2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5–15.6%) and 8.2% (5.5–16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint (ρ = 0.79, P = 0.0021) and trough (ρ = 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concentrations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients.     

血清和肽素水平与急性缺血性卒中患者转归的相关性

目的 探讨血清和肽素水平与急性缺血性卒中患者转归的关系.方法 纳入发病24 h内的首次缺血性卒中患者,应用酶联免疫吸附法检测血清和肽素水平,应用美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评估基线卒中严重程度.在发病后90 d时应用改良Rankin量表(modified Rankin Scale,mRS)评分评价转归,0～2分定义为转归良好.年龄和性别相匹配的健康体检者作为对照者.结果 共纳入连续86例发病24 h内首次缺血性卒中患者和50名年龄和性别相匹配的健康体检者作为对照者.急性缺血性卒中患者发病24 h、7d和14 d血清和肽素水平分别为(7.81±0.66) pmol/L、(4.78±1.76) pmol/L和(2.82±1.42) pmol/L,均显著高于对照组[(1.67±0.56) pmol/L;P均＜0.05].86例患者中,74例(86.05％)转归良好,12例(13.95％)转归不良.转归不良组年龄[(67.64 ±9.62)岁对(61.12±7.31)岁;t=-3.420,P=0.020]、NIHSS评分[(14.16±4.22)分对(6.96±2.04)分;t=-8.26 3,P＜ 0.001]、基线收缩压[(166.06±13.42)mmHg对(154.12±11.69)mmHg;t=5.216,P=0.037;1mmHg=0.133 kPa]、空腹血糖[(8.79±2.98) mmol/L对(6.92±2.24) mmol/L;t=2.076,P=0.041]、C反应蛋白[(7.02±1.72) mg/L对(4.07±1.58) mg/L;t=-1.724,P=0.019]、24 h时和肽素水平[(9.67±2.28)p mol/L对(6.88±2.82)pmol/L;t=13.962,P＜ 0.001]、7d时和肽素水平[(8.22±2.14) pmol/L对(2.97±2.04)pmol/L;t=20.564,P＜0.001]、14 d时和肽素水平[(4.77±1.86)p mol/L对(2.02±0.76) pmol/L;t=8.428,P=0.032]以及心房颤动(33.33％对8.11％;x2=4.986,P=0.036)、大动脉粥样硬化性卒中(41.67％对21.62％;x2 =6.729,P=0.038)、心源性栓塞(33.33％对8.11％;x2=4.986,P=0.036)的患者构成比均显著高于转归良好组,小动脉闭塞性卒中的患者构成比显著低于转归良好组(16.67％对70.27％;x2=16.972,P=0.041).多变量logistic回归分析显示,血清24 h(优势比2.424,95％可信区间1.920 ～ 3.562;P＜0.001)和7d(优势比2.326,95％可信区间1.768 ～3.482;P＜0.001)时和肽素水平以及基线NIHSS评分(优势比2.146,95％可信区间1.616～3.268;P＜0.001)是转归不良的独立危险因素.结论 基线血清和肽素水平增高是急性缺血性卒中患者90 d时转归不良的独立预测因素.     

Teicoplanin pharmacokinetics during albumin dialysis

Teicoplanin (TP) pharmacokinetics was assessed in a critically ill patient during albumin dialysis (AD), which was performed with the molecular adsorbent recirculating system. After a 1200-mg loading dose (24 mg/kg), doses of 1200 and 1000 mg (20 mg/kg) on day 2 and 3, respectively, were administered during two cycles of AD. The mean TP peak and trough concentrations amounted to 99.3 and 21.4 μg/mL, respectively, during AD. A mean half-life of 5.5 h, an apparent volume of distribution of 0.302 L/kg, and a mean total TP clearance of 39 mL/h/kg were calculated. Ninety minutes after the start of AD, the extracorporeal clearance was 3560 mL/h. Within 8 h of AD therapy, the serum concentrations decreased by about 75%. Despite a considerable elimination of TP by AD, therapeutic serum levels could be maintained during the entire treatment by administration of high doses and close monitoring of TP serum concentrations.     

具有生物活性的多价糖肽的研究进展

糖蛋白复合物是许多疾病诊断与治疗中的重要生物标志分子.糖与蛋白之间的作用通常表现出高度特异性和弱的亲和力,化学家们通过合成多价簇状糖来解决糖亲和力太低的问题.本文对近年来代表性的多价糖肽合成工作及其生物应用做了简要概述.     

我院2007-2010年糖肽类抗菌药的使用与革兰阳性球菌的耐药性分析

目的:了解我院糖肽类抗菌药的应用现状和革兰阳性球菌分离率及耐药情况,为临床合理应用抗菌药提供依据。方法:对我院2007-2010年住院患者糖肽类抗菌药的用药频度(DDDs)、销售金额等数据进行统计、分析,并将各科室送检标本检出的革兰阳性球菌分布及药敏试验结果进行汇总。结果:4年来我院住院患者糖肽类抗菌药的DDDs持续增加。4年中分离率在前6位的革兰阳性球菌分别为金黄色葡萄球菌、凝固酶阴性葡萄球菌、肺炎链球菌、粪肠球菌、屎肠球菌、β溶血链球菌;其中金黄色葡萄球菌分离率始终保持在第1位,占所有分离菌的11.0%～14.4%,未发现对万古霉素、利奈唑胺不敏感的葡萄球菌;屎肠球菌的耐药性高于粪肠球菌;耐万古霉素肠球菌(VRE)分离率呈上升趋势。结论:应加强对糖肽类抗菌药合理应用管理,以延缓耐万古霉素葡萄球菌的产生。     

The role of dalbavancin in the multi-disciplinary management of wound infections in orthopaedic surgery

Antimicrobial resistance is continuously increasing among bacterial clinical isolates (especially methicillin resistance in Staphylococcus aureus, MRSA), negatively impacting on outcomes of patients with Surgical Site Infections (SSIs). A multi-disciplinary team work is essential for SSIs prevention and for the choice of antibiotic therapy of orthopaedic SSIs. In particular, an Antibiotic Stewardship (AS) approach is recommended for preserving the activity of old and new antimicrobials. Dalbavancin is a novel antimicrobial agent, belonging to the lipoglycopeptides family, recently approved by FDA for the treatment of ABSSSIs (Acute Bacterial Skin and Skin Structure Infections) and can be considered as a candidate for the treatment of orthopaedic superficial SSIs. An antimicrobial activity directed against MRSA and other multi-resistant Gram-positive pathogens, a bactericidal effect and an extremely extended half-life are among key features of this drug. Dalbavancin gives to clinicians the option to provide an intravenous antimicrobial agent shown to be as effective as conventional therapies, without requiring prolonged admission into the hospital, drastically reducing the length of hospital stay (without reducing the treatment compliance) and total cost per patient. In this paper, we analyze general, microbiological and pharmacological features of dalbavancin, aiming at supporting clinicians while positioning this drug in the context of orthopaedic SSIs.     

The current role of glycopeptides in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in not neutropenic adults: the viewpoint of a group of Italian experts

Staphylococcus aureus is still an important problem in clinical and therapeutic area, worldwide. In Italy, in recent years, methicillin resistance remained stable, yet considerably high, the percentage of strains of MRSA being around 40%. It was deemed interesting and timely to carry out a consensus conference using the RAND/UCLA method to collect the opinion of a group of experts in infectious diseases on the role of glycopeptides in the management of MRSA infections within several clinical scenarios and namely in pneumonia, bacteremia and endocarditis, joint replacement infections, skin and soft tissue infections, diabetic foot, abdominal infections and central nervous system infections. The scenarios proposed by the Scientific Committee have been validated by a group of experts in infectious diseases and then voted in three meetings of infectious disease specialists. The results obtained on each individual condition were analyzed and therapeutic recommendations on each of these were released.