高肌酐清除率重症患者万古霉素血药浓度监测分析

目的：通过分析我院高肌酐清除率重症患者万古霉素血清谷浓度变化,探讨该类患者最优化的万古霉素给药方案。方法：采用回顾性分析研究,选择2016年3月至2016年12月入住我院重症监护室使用并监测万古霉素血清谷浓度的重症患者,对其中肌酐清除率大于120ml/min的患者的一般资料、万古霉素血清谷浓度、疗效等临床资料进行统计分析。结果：共纳入57例患者,共计96次万古霉素血清谷浓度,仅21.88%(21/96)达到目标浓度(15~20mg/L),其中低于15 mg/L者62.50%(60/96),高于20 mg/L者15.62%(15/96)。肌酐清除率相对偏低组(120~149 ml/min),谷浓度达标率及超标率均高于其他组,肌酐清除率＞240ml/min与Ccr120~149 ml/min万古霉素血清谷浓度差异有统计学意义(P＜0.05);多重线性回归分析显示,肌酐清除率、给药剂量及血浆白蛋白时影响万古霉素血清谷浓度的主要因素(P＜0.05),性别、年龄、SOFA评分、血肌酐、总胆红素对万古霉素血清谷浓度的影响无统计学意义(P＞0.05);万古霉素达标者与未达标者病死率比较差异无统计学意义(χ2=0.690,P=0.406)。结论：高肌酐清除率重症患者万古霉素血清谷浓度临床达标率低,需密切监测血药浓度,及时调整治疗方案;肌酐清除率、给药剂量及血浆白蛋白对万古霉素血清谷浓度影响较大,制定给药方案时需考虑这些因素。     

开颅术后患者血清、脑脊液中万古霉素浓度与临床疗效及安全性研究

摘要：目的:探讨开颅术后患者静脉注射万古霉素的血清和脑脊液药物浓度与临床疗效、安全性的关系。方法:采用回顾性研究方法,收集神经外科开颅术后静脉注射万古霉素患者的资料,分析患者万古霉素血药谷浓度、脑脊液浓度及其与临床疗效、不良反应的关系。结果:共收集42例患者,检测脑脊液和血清样本102例次,万古霉素血清谷浓度和脑脊液浓度与给药剂量间关系无统计学意义（P>0.05）,脑脊液中万古霉素浓度在4～8 mg·L-1范围内治疗有效的可能更大（P<0.05）;万古霉素血清谷浓度在低于10 mg·L-1时有效性降低（P<0.05）,且万古霉素血清谷浓度与不良反应发生具有显著的正相关关系（P<0.01）。结论:万古霉素的血清、脑脊液浓度可以为临床治疗提供参考,颅内感染患者需要进行万古霉素治疗药物监测。     

重症感染患者万古霉素不同给药方式血药浓度影响因素分析

目的 探讨不同给药方式下重症感染患者万古霉素血药浓度的影响因素。方法 回顾性分析医院重症医学科2020年2月至2021年2月收治的96例予万古霉素连续静脉注射（CIV,45例）或间歇静脉注射（IIV,51例）治疗的重症感染患者的临床资料,采用简单线性与多重线性回归分析2种给药方式下重症感染患者万古霉素血药浓度的影响因素。结果 CIV患者的血药浓度达标率为73.33%,明显高于IIV患者的49.02%(P <0.05)。简单线性回归分析显示,白蛋白水平、肌酐清除率、首日体质量剂量及年龄、中重度水肿、白蛋白水平、肌酐清除率、首日体质量剂量分别为CIV及IIV患者万古霉素血药浓度的影响因素;多重线性回归分析结果显示,肌酐清除率、首日体质量剂量及肌酐清除率、中重度水肿、首日体质量剂量、白蛋白水平分别为CIV及IIV患者万古霉素血药浓度的独立影响因素。结论 对需使用万古霉素的重症感染患者,CIV相较IIV更易达到有效浓度,独立影响因素（首日体质量剂量、肌酐清除率）更少,且可通过肾功能支持和调整首日给药剂量优化万古霉素的个体化给药方案。     

ICU患者影响万古霉素血药浓度的相关因素分析

目的 通过分析影响重症监护病房(ICU)患者万古霉素血药浓度的相关因素,探讨优化ICU患者万古霉素给药方案。方法 采用回顾性研究方法,收集东莞市人民医院ICU2016年1月至2018年9月使用并监测万古霉素血药浓度的出院患者。统计ICU患者万古霉素血药浓度分布情况,根据肌酐清除率(CrCl)将患者分为CrCl>90mL/min、CrCl 50~90mL/min、CrCl 10~50mL/min及CrCl<10mL/min 4组,分析不同肌酐清除率组对万古霉素血药浓度水平和达标率的影响以及比较指南推荐剂量与实际剂量的差别,并利用多重线性回归分析进一步探讨影响万古霉素血药浓度的相关因素。结果 99例ICU患者监测万古霉素血药浓度共230例次,45例次(19.57%)达到目标浓度(15~20mg/L),72例次(31.30%)未达标(<15mg/L),113例次(49.13%)超标(>20mg/L)。 CrCl 50~90mL/min和CrCl 10~50mL/min组平均血药浓度[(20.16±7.51)mg/L, (23.12±9.37)mg/L]、血药浓度超标比例(45.45%,62.79%)显著高于CrCl>90mL/min组[(14.65±9.07)mg/L, 19.15%]。CrCl>90mL/min、CrCl 50~90mL/min组实际剂量显著低于推荐剂量,而CrCl 10~50mL/min、CrCl<10mL/min组实际剂量显著高于推荐剂量。多重线性回归分析显示,给药剂量(B=11.631,95%CI=7.030~16.232,P<0.001)、肌酐清除率(B=-0.064,95%CI=-0.097~-0.032,P<0.001)、白蛋白水平(B=-0.334,95%CI= -0.634~-0.035,P=0.029)是影响ICU患者万古霉素血药浓度的主要相关因素。结论 ICU患者万古霉素血药浓度达标率较低,在优化ICU患者万古霉素给药方案时应考虑给药剂量、肌酐清除率和白蛋白水平因素的影响。     

肾功能亢进及低蛋白血症对用万古霉素谷浓度的影响

目的 探寻影响万古霉素谷浓度的主要因素,为万古霉素精准治疗提供参考。方法 采用回顾性方法,收集2014年7月到2019年7月中南大学湘雅医院收治的在住院期间使用了万古霉素抗感染治疗并监测了稳态谷浓度的患者的资料。分析影响万古霉素谷浓度的主要因素,探讨肾功能亢进(augmented renal clearance,ARC)和低蛋白血症对万古霉素谷浓度的影响。结果 最终78例患者纳入分析,其中万古霉素谷浓度<10mg/L者50例,10~15mg/L者13例,15~20mg/L者5例,>20mg/L者10例。单因素分析显示低浓度组的年龄较小、矫正肌酐清除率较高,而白蛋白在不同浓度组存在差异。一般线性模型分析表明,矫正肌酐清除率与万古霉素谷浓度负相关,是其浓度不达标的独立影响因素(P=0.018)。ARC组万古霉素谷浓度为(7.5±7.5)mg/L,达标率为11.1%,显著低于非ARC组(56.7%)。低蛋白组万古霉素谷浓度为(8.7±7.8)mg/L,达标率为12.5%,显著低于正常蛋白组(41.9%)。ARC+低蛋白血症组,万古霉素谷浓度为(6.0±1.2)mg/L,达标率为0。结论 肾功能亢进和低蛋血症是降低万古霉素谷浓度的重要因素。使用万古霉素治疗时,应及时识别该两种因素,做好药物浓度监测,优化给药方案。     

肾功能正常患者万古霉素稳态谷浓度分布及影响因素分析

目的 考察肾功能正常患者万古霉素稳态谷浓度的分布情况,明确影响万古霉素稳态谷浓度的相关因素。方法 收集肾功能正常(肌酐清除率≥50mL/min)且接受万古霉素常规给药方案(1g q12h)治疗的感染患者血样,采用酶免疫扩大法测定万古霉素稳态谷浓度,应用有序多元Logistic回归分析万古霉素稳态谷浓度与患者基本资料及生化指标的相关性。结果 纳入331例符合入排标准的感染患者,统计分析发现,41%(136/331)的患者万古霉素稳态谷浓度低于10μg/mL,而稳态谷浓度高于20μg/mL占15%(48/331),仅44%(147/331)的稳态谷浓度达到指南推荐的目标范围(10~20μg/mL)。有序多元Logistic回归结果显示,患者的年龄(P<0.001)、体重(P<0.001)、肌酐清除率(P<0.001)、重症感染(P=0.022)以及高血压(P=0.022)是影响万古霉素稳态谷浓度的危险因素。结论 可以根据患者的年龄、体重、肌酐清除率、感染类型及血压情况来综合调整万古霉素的给药方案,以更好地实现个体化用药。     

万古霉素不同给药方式对革兰阳性菌颅内感染患儿在静脉血与脑脊液中药物谷浓度及疗效的影响

目的:分析万古霉素不同给药方式对革兰阳性菌颅内感染患儿在静脉血与脑脊液中药物谷浓度及疗效的影响.方法:选取2018年1月-2019年12月苏州大学附属儿童医院神经外科收治的确诊或拟诊为革兰阳性菌颅内感染的25例患儿资料,根据万古霉素给药方式的不同将其分为单纯静脉给药组(n=13)、静脉-脑室联合给药组(n=8)和单纯脑室给药组(n=4);比较3组患儿静脉血与脑脊液中万古霉素谷浓度、总显效率与用药疗程.结果:单纯静脉给药组和静脉-脑室联合给药组患儿在静脉血中具有较高的万古霉素谷浓度,分别为(8.92±3.28)和(9.09±4.15)mg/L;静脉-脑室联合给药组和单纯脑室给药组患儿在脑脊液中具有较高的万古霉素谷浓度,分别为(57.27±40.91)和(88.54±40.61)mg/L.单纯静脉给药组、静脉-脑室联合给药组和单纯脑室给药组患儿的总显效率均较高,分别为84.62％、75.00％和100.00％.在用药疗程方面,单纯静脉给药组患儿疗程最长,为(46.46±12.59)d;而静脉-脑室联合给药组和单纯脑室给药组患儿的疗程较为接近.结论:单纯静脉给药较难使颅内感染患儿脑脊液中万古霉素谷浓度达到较满意的水平,而脑室给药可以较好提高脑脊液中万古霉素谷浓度水平,缩短用药疗程,但其改善程度受个体生理病理状况影响.     

万古霉素治疗革兰阳性球菌血流感染患者的血药浓度监测

目的了解本院革兰阳性球菌血流感染患者万古霉素的临床应用及血清谷浓度的监测。方法采用荧光偏振免疫偏振法测定万古霉素血清谷浓度,并结合住院患者的临床资料(基础疾病、病原学结果、万古霉素血清谷浓度、疗效、肾功能情况等),对血流感染革兰阳性球菌并应用万古霉素的25例患者进行回顾性分析。结果血流感染耐甲氧西林金黄色葡萄球菌(MRSA)11例(44.0%),屎肠球菌14例(56.0%);临床治愈率32.0%。25例患者共进行万古霉素血清谷浓度测定38例次,血清谷浓度范围2.99~39.1μg/mL,均值(14.96±7.83)μg/mL,其中达到靶浓度15~20μg/mL者8例(21.0%)。临床治愈组与临床无效组万古霉素血清谷浓度分别为(14.69±7.20)、(15.13±8.53)μg/mL(P=0.85)。肾毒性发生6例(24.0%),APACHEⅡ评分均值17分,均为临床无效组。11例MRSA血流感染中,1例万古霉素最低抑菌浓度(MIC)值为2 mg/L,其余万古霉素MIC值均为1 mg/L;临床治愈组万古霉素曲线下面积(AUC)与MIC浓度比值(AUC/MIC)为209±114。结论按照指南的标准,25例血流感染患者万古霉素血清谷浓度达标率低,需加强对这一类患者血清谷浓度的监测力度,并随时调整用药,给出个体化的用药方案。     

低蛋白血症患儿白蛋白水平对万古霉素血药浓度的影响

[摘要]目的：探讨低蛋白血症患儿白蛋白水平对万古霉素血药浓度的影响,为临床低蛋白血症患儿个体化治疗提供参考。方法：收集2016年5月至2019年5月于四川省自贡市第一人民医院就诊并行万古霉素血药浓度监测的65例患儿临床资料,根据不同白蛋白水平分为低蛋白血症组30例（白蛋白浓度<30 g/L）与正常对照组35例（白蛋白浓度≥30 g/L）,观察两组患儿血浆白蛋白水平、万古霉素谷浓度,记录患儿在不同年龄段对万古霉素血药浓度监测结果的影响及患儿第5次用药后血药浓度在治疗窗内所占比例。采用多元线性回归分析患儿白蛋白水平与万古霉素血药浓度的相关性,观察不良反应发生情况。采用单因素分析与多因素Logistic回归分析万古霉素血药浓度不达标的相关因素。结果：低蛋白血症组患儿平均白蛋白水平、万古霉素谷浓度均低于正常对照组（P<0.05）;两组患儿≤28 d、29 d~1岁、>1~3岁、>3~6岁、>6~12岁万古霉素谷浓度组间比较差异有统计学意义（P<0.05）,低蛋白血症组>3~6岁、>6~12岁万古霉素谷浓度低于正常对照组（P<0.05）,其中低蛋白血症组万古霉素谷浓度在治疗窗内为26.67%（8/30）,正常对照组为42.86%（15/35）,差异无统计学意义（P>0.05）。Spearman相关分析结果显示,患儿白蛋白水平与万古霉素血药浓度呈正相关（P<0.05）;7例患儿出现肝酶升高、3例皮疹、2例白细胞减少。多因素Logistic回归分析结果显示,药物用法用量不合理、合并基础疾病是导致万古霉素血药浓度不达标的独立危险因素（P<0.05）。结论：低蛋白血症患儿受多因素影响,万古霉素血药浓度个体差异较大,临床应积极监测低蛋白血症患儿血药浓度,以调整用药。     

癫痫患者血浆丙戊酸钠稳态谷浓度影响因素分析

目的:探讨癫痫患者口服丙戊酸钠(VPA)稳态谷浓度与体内病理生理因素以及联合用药的相关性,为临床合理使用VPA提供参考依据。方法:采用回顾性调查方法在空军总医院收集30例因癫痫口服VPA的患者病历资料,记录患者性别、年龄、VPA单位体重剂量、血药浓度及相应生化检验值。应用SAS软件(6.04版)对数据进行多元线性回归分析。结果:VPA稳态谷浓度与血清白蛋白(ALB)、单位体重剂量(mg.kg-1)具有显著正相关性(P<0.05);与肝药酶诱导剂具有显著负相关性(P<0.05)。结论:临床使用VPA时应重点考虑ALB、单位体重剂量和肝药酶诱导剂对VPA血药浓度的影响,定期监测其血药浓度。     

Role of glutathione in reduction of arsenate and of gamma-glutamyltranspeptidase in disposition of arsenite in rats

Arsenate (AsV), the environmentally prevalent form of arsenic, is converted sequentially in the body to arsenite (AsIII), monomethylarsonic acid (MMAsV), monomethylarsonous acid (MMAsIII), and dimethylarsinic acid (DMAsV) and some trimethylated metabolites. Although the biliary excretion of arsenic in rats is known to be glutathione (GSH)-dependent, involving transport of arsenic-GSH conjugates, the role of GSH in the reduction of AsV to the more toxic AsIII in vivo has not been defined. Therefore, we studied how the fate of AsV is influenced by buthionine sulfoximine (BSO), which depletes GSH in tissues. Control and BSO-treated rats were given AsV (50 micromol/kg, i.v.) and arsenic metabolites in bile, urine, blood and tissues were analysed by HPLC-HG-AFS. BSO increased retention of AsV in blood and tissues and decreased appearance of AsIII in blood, bile (by 96%) and urine (by 63%). The biliary excretion of MMAsIII was also nearly abolished, the appearance of MMAsIII and MMAsV in the blood was delayed and the renal concentrations of these monomethylated arsenicals were decreased by BSO. Interestingly, appearance of DMAsV in blood and urine remained unchanged and the concentrations of this metabolite in the kidneys and muscle were even increased in response to BSO. To test the role of gamma-glutamyltranspeptidase (GGT) in arsenic disposition, the effect of the of the GGT inhibitor acivicin was investigated in rats injected with AsIII (50 micromol/kg, i.v.). Acivicin lowered the hepatic and renal GGT activities and increased the biliary as well as urinary excretion of GSH, but failed to alter the disposition (i.e. blood and tissue concentrations, biliary and urinary excretion) of AsIII and its metabolites. In conclusion, shortage of GSH decreases not only the hepatobiliary transport of arsenic, but also reduction of AsV and the formation of monomethylated arsenic, while not hindering the production of dimethylated arsenic. While GSH plays an important role in the disposition and toxicity of arsenic, GGT, which hydrolyses GSH and GSH conjugates, apparently does not influence the fate of the GSH-reactive trivalent arsenicals in rats.     

微透析取样技术在中药体内分析中的应用研究进展

本文综述了微透析取样技术在中药体内分析中的应用,介绍微透析取样技术的原理、组成、探针类型、特点,重点阐述了微透析取样技术在测定脑、血液、皮肤等组织器官中中药有效成分浓度的应用实例。表明微透析取样技术在中药药效研究中具有广阔的前景。     

应用PASS系统分析我院2010年住院医嘱

目的:了解我院2010年住院患者的合理用药情况,探讨如何利用合理用药监测系统( PASS)提高合理用药水平.方法:利用PASS对我院2010年15 966例住院患者的1 184 997条用药医嘱进行监测,以黑色警示医嘱为依据,收集不合理用药信息,并对监测结果进行统计、分析.结果:不合理用药医嘱50 261条,发生率为4.24％.绝对禁止黑色医嘱5441条,主要为药物相互作用(66.54％)、注射液体外配伍(17.86％)、用法用量(15.46％)、儿童警告(1.14％).结论:应用PASS系统能有效监测医嘱中的不合理用药情况,有利于提高临床合理用药水平,但PASS系统尚存在局限性,有待进一步完善.     

Changes in levels of dependency and predictors of mortality in elderly people in institutional care in Dunedin

The 1983 study of dependency of subjects in institutional care in Dunedin was repeated two years later. A significant increase in levels of dependency in residential homes, particularly in the Religious and Welfare sector was found. In 1983 there were 29 high dependency residents and 73 medium dependency residents in residential homes. In 1985 these numbers had increased to 55 and 86 respectively. There was no change in the number of low dependency residents. In 1983, 6 high dependency residents had been admitted to residential home care in the year prior to the study. In 1985 the number of high dependency residents recently admitted had increased to 23. There had also been a significant increase in the dependency of patients in Religious and Welfare continuing care hospitals. Of the 933 subjects in institutional care in 1983 who were able to be followed, 354 (37.9%) died in the following 2 years. Mortality rate was higher for those in hospital care (48.1%) than for those in residential home care (29.6%). Mortality rates were higher in more dependent subjects and this was evident for each measure of dependency.     

应用PASS系统对我院2008年住院医嘱的分析

目的监测分析2008年我院住院患者用药情况。方法将PASS系统嵌入医生工作站、临床药学工作站等子系统,构建合理用药计算机网络系统,对住院医嘱进行及时监测,将监测结果向医生反馈,并对其进行统计、分析。结果2008年共监测医嘱3 620 241条,不合理医嘱908条,占0.02%。不合理医嘱中,配伍禁忌(381条)占41.96%,用法用量(381条)占41.96%,药物相互作用(108条)占11.89%,儿童用药(38条)占4.19%。经与医生沟通后,更改不合理医嘱856条,占94.27%。结论PASS系统可有效监测医嘱中的不合理用药,通过与医生交流,大大减少药物不良事件的发生,值得临床推广应用,也为临床药师开展工作带来了极大的便利。但PASS系统尚存在局限性,有待进一步完善。     

Role of desacetylation in the detoxification of cephalothin in renal cells in culture

The toxicity of three cephalosporin antibiotics to rabbit kidney cells in culture was compared to their known nephrotoxic potential in vivo (cephaloridine greater than cefazolin greater than cephalothin). While cephalothin is considered to be a relatively nonnephrotoxic cephalosporin when administered to many species including humans and rabbits, in several in vitro systems involving rabbit renal tissue, cephalothin was comparatively more toxic than anticipated based on in vivo data. Cephalothin is extensively desacetylated in rabbits to a less microbiologically active metabolite, desacetylcephalothin. When a microsomal S9 fraction from rabbit kidney was added to the in vitro assay in cultured rabbit renal cells, cephalothin was desacetylated and its toxicity to kidney cells was reduced. The addition of S9 in vitro provided a toxicity ranking of the cephalosporins that correlated with their known in vivo nephrotoxic potentials (cephaloridine greater than cefazolin greater than cephalothin). The in vitro detoxification of cephalothin by S9 was blocked by the coadministration of the esterase inhibitor, aminocarb. Desacetylcephalothin was relatively nontoxic to rabbit renal tissue in vitro. These results suggest that the desacetylation of cephalothin in vivo represents a previously unrecognized mechanism of detoxification of this cephalosporin antibiotic. Furthermore, this mechanism of detoxification may be applicable to other acetylated cephalosporins.     

2009年某院住院患者抗真菌药用药调查

目的:分析讨论某院抗真菌药使用的合理性,为临床安全有效地使用抗真菌药提供参考。方法:回顾性统计分析某院2009年住院患者抗真菌药用药信息。结果:2009年某院住院患者抗真菌药DDDs排名前3名分别为:氟康唑、制霉菌素和伊曲康唑;使用金额排名前3名分别为:氟康唑、米卡芬净及卡泊芬净;更换一种抗真菌药进行治疗的患者数为176人,在全部患者中占13.4%。结论:应进一步强化用药指征的意识,提高标本送检率,同时改善某些抗真菌用药不合理更换的现象,以避免耐药性发生,从而更好更长远地体现抗真菌药的治疗价值。     

Kinetics of in vitro metabolism of methoxyphenamine in rats

1. Methoxyphenamine (MP) was metabolized in vitro by rat liver preparations to O-desmethylmethoxyphenamine (O-desmethyl-MP), N-desmethylmethoxyphenamine (N-desmethyl-MP) and 5-hydroxymethoxyphenamine (5-hydroxy-MP). These metabolic pathways were inhibited by SKF 525-A and carbon monoxide, which indicates that these reactions were mediated at least partly by an NADPH-dependent cytochrome P-450 system. 2. Strain differences in the metabolism of this drug in vitro were observed in female Lewis and Dark Agouti (DA) rats, which are proposed models for human debrisoquine phenotypes. Methoxyphenamine O-demethylase and 5-hydroxylase activity in DA rats were lower than those in Lewis rats. 3. The metabolic transformation of methoxyphenamine in vitro to O-desmethyl-MP was inhibited competitively by debrisoquine and sparteine. This indicates that the cytochrome P-450 isoenzyme mediating the metabolism of MP to O-desmethyl-MP is similar to that mediating metabolism of debrisoquine and sparteine. However, no inhibition was observed with methenytoin.     

Comparison of in vitro cell models in predicting in vivo brain entry of drugs

Although several in vitro models have been reported to predict the ability of drug candidates to cross the blood-brain barrier, their real in vivo relevance has rarely been evaluated. The present study demonstrates the in vivo relevance of simple unidirectional permeability coefficient (P(app)) determined in three in vitro cell models (BBMEC, Caco-2 and MDCKII-MDR1) for nine model drugs (alprenolol, atenolol, metoprolol, pindolol, entacapone, tolcapone, baclofen, midazolam and ondansetron) by using dual probe microdialysis in the rat brain and blood as an in vivo measure. There was a clear correlation between the P(app) and the unbound brain/blood ratios determined by in vivo microdialysis (BBMEC r=0.99, Caco-2 r=0.91 and MDCKII-MDR1 r=0.85). Despite of the substantial differences in the absolute in vitro P(app) values and regardless of the method used (side-by-side vs. filter insert system), the capability of the in vitro models to rank order drugs was similar. By this approach, thus, the additional value offered by the true endothelial cell model (BBMEC) remains obscure. The present results also highlight the need of both in vitro as well as in vivo methods in characterization of blood-brain barrier passage of new drug candidates.