Mohnarin2009年度报告:门急诊患者来源细菌耐药监测

目的 了解我国门急诊患者分离细菌的耐药状况与发展趋势.方法 监测2009年度卫生部全国细菌耐药监测网(Mohnarin)所属114所医院临床分离细菌耐药状况,采用标准纸片扩散法或自动化临床微生物方法,测定细菌敏感性,依据CISI 2009年标准,以WHONET 5.5软件进行数据分析.结果 114所医院按照监测方案共获得临床分离菌9929株,其中革兰阴性菌6109株(61.5%);革兰阳性菌3820株(38.5%).最常见的细菌依次为大肠埃希菌、肺炎克雷伯菌、金黄色葡萄球菌、铜绿假单胞菌与表皮葡萄球菌.耐甲氧西林金黄色葡萄球菌、表皮葡萄球菌及溶血葡萄球菌的检出率分别为45.6%,69.8%和68.1%;未发现万古霉素耐药葡萄球菌.粪肠球菌和屎肠球菌对万古霉素耐药率分别为1.2%和3.1%;未发现利奈唑胺耐药肠球菌.肺炎链球菌对青霉素的敏感率>60.0%.大肠埃希菌及肺炎克雷伯菌产ESBL比率分别为51.7%和45.9%.有0.3%的大肠埃希菌和0.7%的肺炎克雷伯菌对亚胺培南耐药.铜绿假单胞菌对碳青酶烯类的耐药率约20%;鲍曼不动杆菌对其耐药率大多>50%.结论 我国门急诊来源病原菌以大肠埃希菌、肺炎克雷伯菌、金黄色葡萄球菌、铜绿假单胞菌多见;门急诊来源MRSA的发生率较2008年低;但大肠埃希菌和肺炎克雷伯菌ESBLs的阳性率高于2008年.     

2017年某医院细菌耐药性监测的分析

目的了解某医院临床分离细菌的分布特点及耐药情况,为临床合理使用抗菌药物提供参考。方法收集 2017年全年自贡市第一人民医院微生物室分离的临床菌株及药敏结果,采用 WHONET 5.6软件对数据进行分析统计。结果 2017年共分离出细菌 3 679株,其中革兰阳性菌 1 033株,占 28.1%,革兰阴性菌 2 646株,占 71.9%。分离菌中排名前 5位的细菌分别是大肠埃希菌( 26.7%)、金黄色葡萄球菌( 10.6%)、肺炎克雷伯菌( 10.6%)、铜绿假单胞菌( 9.2%)和肺炎链球菌( 7.0%)。标本类型以痰液和尿液为主,其中痰液以铜绿假单胞菌和肺炎克雷伯菌为主,而尿液以大肠埃希菌和肺炎克雷伯菌为主。分离细菌最多的科室为儿科,占 17.6%,其次是普通外科( 9.3%)和泌尿外科( 6.6%),儿科以金黄色葡萄球菌和肺炎链球菌为主,而普通外科和泌尿外科均以大肠埃希菌为首位。常见革兰阳性菌耐药监测结果为:未分离出耐万古霉素、利奈唑胺或奎奴普丁 /达福普汀的金黄色葡萄球菌和肺炎链球菌,其中耐甲氧西林金黄色葡萄球菌( MRSA)的检出率为 19.9%,而耐青霉素肺炎链球菌的检出率为 0%。而肠球菌中屎肠球菌较粪肠球菌对常见抗菌药物耐药率更高(除外四环素和利奈唑胺),两者对万古霉素和利奈唑胺的耐药率均较低(＜ 4.0%)其中粪肠球菌对万古霉素耐药率为 0%。常见革兰阴性菌耐药结果为:大肠埃希菌和肺炎克雷伯菌对头孢吡肟、哌拉西林 /他唑巴,坦、碳青霉烯类及氨基糖苷类耐药率均较低(＜ 10%),其中产超广谱 β?内酰胺酶( ESBL)的菌株分别占 43.3%和 20.8%,且产 ESBL菌株较不产 ESBL菌株对常见抗菌药物耐药率高;而铜绿假单胞菌对常见抗菌药物耐药率较低,对左氧氟沙星、庆大霉素、妥布霉素、阿米卡星敏感率均为 90%以上。结论临床分离菌以革兰阴性菌为主。不同科室及标本类型的常见分离菌的差异较大,临床应根据病原菌的分布特点及耐药性合理选择抗菌药物。     

2019年自贡市第一人民医院细菌耐药性监测

目的 了解自贡市第一人民医院2019年临床分离细菌耐药性。方法 收集该院2019年临床菌株及药敏结果,以美国临床和实验室标准化协会(CLSI)2019年折点作为细菌药敏的判断标准,采用WHONET5.6及SPSS23软件对数据进行分析统计。结果 共分离出4189株,其中革兰阳性菌1301株,占31.1%;革兰阴性菌2888株,占68.9%。排名前5位细菌分别为大肠埃希菌、金黄色葡萄球菌、肺炎克雷伯菌、铜绿假单胞菌和肺炎链球菌。分离菌的标本类型以痰液和尿液为主,革兰阳性菌耐药情况：耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)的检出率分别为23.1%和81.1%,未发现耐万古霉素或利奈唑胺的菌株;肠球菌属中分离出3株耐利奈唑胺的粪肠球菌,未分离出耐万古霉素的屎肠球菌和粪肠球菌;分离出1株耐青霉素的肺炎链球菌。革兰阴性菌耐药情况：大肠埃希菌和肺炎克雷伯菌对碳青霉烯类抗生素高度敏感,耐药率分别为1.1%和3.0%,产超广谱β-内酰胺酶(ESBLs)菌株的检出率分别为39.5%和12.1%;非发酵糖革兰阴性杆菌中,铜绿假单胞菌对常见抗菌药物耐药率低于鲍曼不动杆菌,其中耐碳青霉烯类铜绿假单胞菌和耐碳青霉烯类鲍曼不动杆菌的检出率分别为9.8%和65.8%;流感嗜血菌和黏膜炎莫拉菌多见于儿童,其中产β-内酰胺酶菌株检出率较高,分别为73.4%和97.7%。结论 临床分离菌以革兰阴性菌为主,流感嗜血菌和黏膜炎莫拉菌产β-内酰胺酶比率高;同时鲍曼不动杆菌对碳青霉烯类抗生素耐药率高,医院感染管理部门应采取相应措施,以减少其流行暴发。     

卫生部全国细菌耐药监测网2011年血流感染细菌耐药监测

目的了解血流感染病原菌分布和细菌耐药情况。方法监测2011年度全国149家医院,血标本来源细菌药敏结果用CLSI 2011年标准判读,用WHO-NET 5.6软件进行药物敏感性分析。结果共获得29837株病原菌,其中革兰阳性菌15593株,占51.2%,革兰阴性菌14863株,占48.8%。最常见细菌依次为凝固酶阴性葡萄球菌、大肠埃希菌、肺炎克雷伯菌、金黄色葡萄球及鲍曼不动杆菌。耐甲氧西林金黄色葡萄球菌和凝固酶阴性葡萄球菌的检出率分别为51.3%和80.3%。未发现万古霉素耐药葡萄球菌。粪肠球菌和屎肠球菌对万古霉素耐药率分别为1.8%和6.9%。未发现利奈唑胺耐药肠球菌。大肠埃希菌和肺炎克雷伯菌对亚胺培南耐药率分别为2.9%和12.0%,对美罗培南耐药率分别为3.4%和10.6%。铜绿假单胞菌对碳青霉烯类的耐药率约20%,鲍曼不动杆菌耐药率超过铜绿假单胞菌。结论本年度血培养分离细菌耐药现象较为普遍,耐万古霉素肠球菌的检出率较2010年有所增加。     

188例感染性心内膜炎血培养阳性的病原菌分布及药敏分析

目的考查本地区近五年来感染性心内膜炎(infective endocarditis,IE)的致病菌分布特点及药敏情况,为临床选择抗菌药物提供参考。方法通过医院电子病历系统筛选我院自2007年1月至2011年12月确诊为IE并经血培养阳性的病例,对其致病菌及药敏结果进行回顾性分析。结果革兰氏阳性菌占IE致病菌的82.4%,其中链球菌40.4%、葡萄球菌24.4%、肠球菌10.6%;革兰氏阴性菌占10.1%,主要是肺炎克雷伯菌3.19%、大肠埃希菌2.12%和铜绿假单胞菌2.12%;真菌占7.4%,主要是念珠菌感染3.19%;药敏结果:链球菌对青霉素敏感率为96.1%,对红霉素和四环素耐药率分别38.2%和45.7%;金黄色葡萄球菌对青霉素耐药率为93.1%,耐甲氧西林金黄色葡萄球菌(methicillin resistant staphylococcusanrens,MRSA)20.7%;均无发现对万古霉素、替考拉宁和利奈唑胺耐药菌株;大肠埃希菌和铜绿假单胞菌对三代头孢耐药率分别为50%和100%。结论链球菌依然是感染IE最常见的致病菌,其次是葡萄球菌和肠球菌;青霉素仍然是链球菌感染IE的首选药物,而金黄色葡萄球菌感染则应避免使用青霉素,但对氧氟沙星、利福平、氨基苷类仍保持有较高的敏感率。链球菌对红霉素和四环素、大肠埃希菌和铜绿假单胞菌对三代头孢的耐药情况应引起重视。     

Mohnarin2009年度报告:北京地区细菌耐药监测

目的 掌握北京地区细菌耐药状况与发展趋势.方法 监测2009年度北京地区11所医院临床分离细菌耐药状况,细菌敏感性测定,用标准纸片扩散法或自动化临床微生物测定方法,以Whonet 5.5软件进行数据分析.结果 共获得临床分离菌28036株,其中革兰阴性菌19170株,占68.4%;革兰阳性菌8866株,占31.6%.最常见的细菌依次为铜绿假单胞菌、大肠埃希菌、鲍曼不动杆菌、金黄色葡萄球菌和肺炎克雷伯菌.耐甲氧西林金黄色葡萄球菌与凝固酶阴性葡萄球菌的发生率分别为55.5%和66.9%;未发现万古霉素耐药葡萄球菌.粪肠球菌和屎肠球菌对万古霉素耐药率分别为0.3%和11.1%;未发现利奈唑胺耐药肠球菌.耐青霉素肺炎链球菌比率为6.9%.大肠埃希菌及肺炎克雷伯菌产ESBIL比率分别为64.3%和46.6%.有0.6%的大肠埃希菌和1.3%的肺炎克雷伯菌对亚胺培南耐药.铜绿假单胞菌对碳青酶烯类的耐药率约30%;鲍曼不动杆菌耐药率超过铜绿假单胞菌.结论 本年度北京地区临床分离细菌耐药现象较为普遍且革兰阴性菌耐药率仍呈上升趋势.     

卫生部全国细菌耐药监测网2010年北京地区细菌耐药监测

目的 总结北京地区细菌耐药状况与发展趋势.方法 监测2010年度北京地区14所医院临床分离细菌耐药状况,细菌敏感性测定采用标准纸片扩散法或自动化临床微生物测定方法,以WHONET 5.6软件进行数据分析.结果 共获得临床分离菌31754株,革兰阴性菌20733株,占65.3％;革兰阳性菌11021株,占34.7％.最常见的细菌依次为大肠埃希菌、铜绿假单胞菌、鲍曼不动杆菌、金黄色葡萄球菌和肺炎克雷伯菌.耐甲氧西林金黄色葡萄球菌与凝固酶阴性葡萄球菌的发生率分别为56.3％和83.2％;未发现万古霉素耐药葡萄球菌.粪肠球菌和屎肠球菌对万古霉素耐药率分别为0.7％和14.8％,未发现利奈唑胺耐药肠球菌.耐青霉素肺炎链球菌比率为8.7％.有8.9％和0.4％的大肠埃希菌及16.2％和2.5％的肺炎克雷伯菌对亚胺培南和美罗培南耐药.铜绿假单胞菌对碳青酶烯类的耐药率约30％,鲍曼不动杆菌耐药率超过铜绿假单胞菌.结论 本年度北京地区临床分离细菌耐药现象仍较为普遍,但同上年度相比,大多数细菌耐药率未呈上升趋势.耐万古霉素的肠球菌和葡萄球菌检出率有所增加.     

中国西部地区血流感染病原菌分布及耐药性

目的 了解中国西部血流感染病原菌的分布及耐药性。方法 中国西部10家医院血标本临床分离菌株,采用 标准纸片扩散法或自动化仪器检测法,按照统一技术方案测定监测药物对细菌的敏感性,依据CLSI M100 2016年标准,用 WHONET 5.6软件进行数据分析。结果 10家医院2016—2017年血标本中共获分离菌10504株,其中革兰阳性菌占42%,革兰 阴性菌占58%,其中肠杆菌科细菌48.4%,非发酵糖革兰阴性菌9.0%,其他革兰阴性菌1.4%。居前10位的分离菌依次为大肠埃 希菌(28.9%)、凝固酶阴性葡萄球菌(CNS)(20.3%)、克雷伯菌属(12.7%)、肠球菌属(7.4%)、金黄色葡萄球菌(7.3%)、不动杆菌属 (3.7%)、肠杆菌属(3.2%)、铜绿假单胞菌(3.1%)、β-溶血链球菌(2.5%)和其他链球菌(1.5%),占所有分离菌株的90.6%。耐甲氧西 林金黄色葡萄球菌(MRSA)、耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)分别占金黄色葡萄球菌和凝固酶阴性葡萄球菌的32.9%和 74.9%。粪肠球菌对高浓度庆大霉素和氨苄西林的耐药率分别为46.6%和6.9%,屎肠球菌对多数测试药物的耐药率显著高于粪肠 球菌。草绿色链球菌对青霉素的耐药率为8.9%。肺炎链球菌对青霉素的耐药率为3.4%。金黄色葡萄球菌、β-溶血链球菌、肺炎 链球菌和其他链球菌属中均未发现万古霉素和利奈唑胺耐药菌株,未发现万古霉素耐药的粪肠球菌,屎肠球菌对万古霉素的耐 药率为2%,粪肠球菌和屎肠球菌对利奈唑胺的耐药率分别为1.6%和0.4%。大肠埃希菌、肠杆菌属、沙雷菌属、变形菌属和柠 檬酸菌属等肠杆菌科细菌对碳青霉烯类的耐药率为0.7%~13.3%。非发酵糖革兰阴性菌对碳青霉烯类耐药率较高,铜绿假单胞菌 对碳青霉烯类的耐药率20%左右,不动杆菌属耐药率为68%左右。结论 2016—2017年中国西部地区监测资料显示血流感染分 离菌仍以革兰阴性菌为主,血流感染分离株对常用抗菌药物耐药性仍严重。     

2016年大理白族自治州人民医院细菌耐药性监测

目的了解2016年大理白族自治州人民医院临床分离细菌分布特征及主要病原菌的耐药现状。方法采用Vitek-2细菌鉴定药敏分析仪,ATB手工药敏条和纸片扩散法进行菌株鉴定或药敏试验,并用WHONET5.6统计软件进行数据统计。结果共收集菌株2496株,革兰阴性菌1543株(61.8%),革兰阳性菌953株(38.2%)。分离率排列前5位的依次是大肠埃希菌(26.5%)、肺炎克雷伯菌(8.1%)、金黄色葡萄球菌(7.7%)、铜绿假单胞菌(6.5%)和肺炎链球菌(5.7%)。耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)的检出率分别为38.7%和78.2%,未发现对万古霉素、利奈唑胺及替加环素耐药的葡萄球菌。屎肠球菌检出率高于粪肠球菌,屎肠球菌对青霉素G及氨苄西林高度耐药,粪肠球菌对青霉素G及氨苄西林高度敏感,检出两株耐万古霉素的屎肠球菌(2.1%)。肺炎链球菌非脑膜炎分离株儿童组及成年组对青霉素耐药率分别为3.8%、9.4%。大肠埃希菌、肺炎克雷伯菌及奇异变形杆菌ESBL阳性检出率分别为59.2%、58.9%和28.1%,肺炎克雷伯菌及阴沟肠杆菌中检出少量碳青霉烯类耐药的肠杆菌科细菌(CRE),检出率分别为1.0%和9.8%。铜绿假单胞菌及鲍曼不动杆菌对碳青霉烯类抗生素耐药率分别为21.7%、67.0%。结论大理地区细菌耐药性监测结果较其它地区存在差异,应做好本地区细菌耐药性监测,利用本地区监测结果指导临床合理使用抗生素。     

医院感染多重耐药菌分布及耐药性分析

目的 了解医院感染多重耐药菌分布及耐药性分析,为临床诊疗提供依据.方法 25 618例临床感染标本分离株培养鉴定后,监测常见分离菌的多重耐药菌株(MDRO).结果 1 087株分离菌以革兰阴性菌925株为主,革兰阳性菌162株.革兰阴性菌中分离率前5位分别是肺炎克雷伯菌、大肠埃希菌、铜绿假单胞菌、鲍曼不动杆菌、阴沟肠杆菌.革兰阳性菌中分离率前5位分别是金黄色葡萄球菌、凝固酶阴性葡萄球菌、肺炎链球菌、屎肠球菌、粪肠球菌.大肠埃希菌、肺炎克雷伯菌产超广谱β-内酰胺酶(ESBLs)株的检出率分别为75.53％、37.14％;金黄色葡萄球菌中耐甲氧西林的金黄色葡萄球菌(MRSA)的检出率为78.20％,凝固酶阴性葡萄球菌中耐甲氧西林的凝固酶阴性葡萄球菌(MRCNS)的检出率为84.60％.13株屎肠球菌中发现3株万古霉素耐药株(VRE).结论 医院感染多重耐药菌分布主要以革兰氏阴性杆菌为主,其次是革兰氏阳性球菌.MDRO的增多是医院面临的重要问题,在临床上应改进治疗手段,合理使用抗菌药物,减少MDRO的产生和播散.     

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.