万古霉素MIC漂移(Judy)ppt课件
万古霉素PPT精选课件
• 仅在下列况下需要进行治疗药物监测： • 1.病人同时使用氨基糖苷类抗生素 • 2.病人的药代动力学参数（可能）改变 • 3.病人在治疗期间需要进行血液透析 • 4.短期大剂量或长期使用万古霉素治疗 • 5.病人有肾功能不全 • 在这些情况下，需要测量血药最低浓度
29
• 近年来学界改变了治疗时万古霉素血药浓 度水平的标准。早期的学者认为治疗期间， 万古霉素的血药峰浓度应该在30-40mg/L， 最低浓度在5-10mg/L。最新的建议为，在 用于治疗炎症感染是，不需要限制血药峰 浓度，最低浓度应该在15-20mg/L。
33
耳毒性
• 确定万古霉素引起的耳毒性症状的几率更 加的困难，因为缺少有说服力的病例。普 遍的观点是，万古霉素极少引起耳毒性症 状。 万古霉素血药浓度与耳毒性的相关性 也是不确定的。有的病例在万古霉素血清 浓度超过 80 µg/mL时产生耳毒性症状，可 是同样有在治疗安全范围的血清浓度下产 生耳毒性病例的报告。因此，不能证明使 用治疗药物检测的方法保持治疗安全范围 的血药浓度可以防止耳毒性症状的发生。
• 6、与其他抗生素无交叉耐药性，极少耐药菌株。主要用 于心内膜炎、败血症、伪膜性肠炎等。
• 7、药品口服不吸收，静滴时必须先用注射用水溶解，滴 注时间不得少于1小时。静滴过快有皮肤反应，浓度过高 可致血栓性静脉炎；肌注可致剧烈疼痛，故不可肌注；有 严重耳毒性及肾毒性，故只宜短期用于抢救。
24
• 由于以下几个原因，万古霉素从来没有成 为治疗金黄色葡萄球菌感染的一线药物：
34
谢谢关注
Office
Make Presentation much more fun
@WPS官方微博
@kingsoft3w5ps
颅内感染与万古霉素的应用ppt课件
谢谢
SUCCESS
THANK YOU
2019/6/14
325谷浓度谷浓度15mgl15mgl是是肾毒性的独立危险因素肾毒性的独立危险因素hidayatlkarchinternmed2006常规剂量单药引起常规剂量单药引起肾毒性少见肾毒性少见hidayatlkarchinternmed2006金黄色葡萄球菌暴露于万古霉素谷浓度10mgl时可产生具有万古霉素低耐药金葡菌visa样特点的菌株推荐其血药谷浓度应保持在10mgl以避免发生耐药tdmtdm适用于接受大剂量治疗以持续维持谷浓度在1520mgl或具有发生肾毒性危险的患者对于肾功能不稳定肾功能恶化或显著改善的患者和接受长期治疗35天的患者推荐tdm短期治疗5天或低强度治疗目标谷浓度15mgl的患者不推荐频繁监测复杂感染要充分考虑治疗失败的可能性应特别关注具体病例感染菌株的mic值不仅要考虑抗菌药物对细菌的敏感性及药动学与药效学对治疗的影响还应考虑到临床更复杂的情况延长给药间歇时间而每次药物剂量不变简便适用治疗浓度范围广和血浆半衰期长的药物计算公式为
对于肾功能不稳定（肾功能恶化或显著改善）的 患者和接受长期治疗（＞3-5天）的患者，推荐 TDM
短期治疗（＜5天）或低强度治疗（目标谷浓度＜ 15mg/L）的患者，不推荐频繁监测
提示
尽量避免小剂量应用万古霉素
复杂感染要充分考虑治疗失败的可能性，应特 别关注具体病例感染菌株的MIC值
常用于治疗院内感染的抗生素
亚胺培南（泰能） 头孢他定（凯复定） 头孢哌酮-舒巴坦 头孢吡肟 头孢曲松
均不能有效覆盖G+中占相当比例的MRSA 和MRSE
李家泰，金少鸿，汪复，张秀珍
MRSA/MRSE感染可能是致命的
MRSA/MRSE 感染： 程度重、病程长、持续发热、伤后 不愈合 使用多种抗生素感染仍旧难以 控制 死亡率可高达34~50%
万古霉素合理使用ppt课件
Formula
• actual body weitht,ABW • IBW理想体重（ideal body weight） (kg)
Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet. Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet. • ABW 调整体重 adjusted body weight (kg) If the actual body weight is greater than 30% of the calculated IBW, calculate the adjusted body weight (ABW): ABW = IBW + 0.4(actual weight - IBW) • The IBW and ABW 用于肥胖病人的药物剂量计算
最低血药浓度持续超过 30μg/mL以上，可出现 肾、听力损害等副作用。
10-20ug/ml（共识）
给药途径
• 口服不吸收：125mg qid;500mg,qid • 静脉滴注 • 脑室内注射：10mg/d*9d，浓度可达
606mg/L
• 输注顺序：PH3-5稳定 • 氨茶碱、磷酸地塞米松、苯巴比妥及碱性
万古霉素合理使用
• 正确的病人： • 正确的药物： • 正确的用法： • 正确的时间： • 正确的途径：
正确的病人
• 说明书：MRSA及其它细菌所致的感染
• 对金葡菌、凝固酶阴性葡萄球菌、化脓链球菌、 肺炎链球菌、草绿色链球菌等多数革兰氏阳性菌 包括耐β-内酰胺类抗生素的菌株具有杀菌作用；
• 对肠球菌属的生长具有抑制作用； • 革兰阳性杆菌如白喉杆菌等棒状杆菌； • 厌氧革兰阳性杆菌：艰难梭菌，放线菌属，李斯
外科用“来可信”-注射用盐酸万古霉素PPT
手术部位感染（surgical site infection, SSI)是指发生在切口或手术深部器官或腔隙的感染 SSI约占全部医院感染的15% 约占外科病人医院感染的35%40%
切口浅部感染
#2022
单击此处可添加副标题
切口深部感染 术后30天内（如有人工植入物＊则术后1年内）发生、累及切口深部筋膜及肌层的感染，并至少具备下述情况之一者： 从切口深部流出脓液 切口深部自行裂开或由医师主动打开，且具备下列症状体征之一：①体温> 38℃；②局部疼痛或压痛 床或经手术或病理组织学或影像学诊断发现切口深部有脓肿 外科医师诊断为切口深部感染 感染同时累及切口浅部及深部者，应列为深部感染
糖尿病患者
神经外科术后感染
其中MRCNS占75.7%，MRSA占55.6% 《中华医院感染学杂志》 2008，18（9）
03
添加标题
均应报告耐药，而不考虑其体外药敏结果”。
04
住院患者MRSA检出率逐年升高
全国60家三甲医院数据
中检所和国家细菌耐药监测中心数据 中国抗生素杂志2003：28（4）
MRSA感染的易感人群
免疫功能受损或免疫缺陷患者
新生儿、老年人
有创口的外科患者、严重烧伤患者
粒细胞减少者、恶性肿瘤患者
单击此处添加大标题内容
官／腔隙感染 术后30天内（如有人工植入物＊则术后1年内）、发生在手术曾涉及部位的器官或腔隙的感染，通过手术打开或其他手术处理，并至少具备以下情况之一者： 放置于器官／腔隙的引流管有脓性引流物 器官／腔隙的液体或组织培养有致病菌 经手术或病理组织学或影像学诊断器官／腔隙有脓肿 外科医师诊断为器官／腔隙感染 人工植入物指人工心脏瓣膜、人工血管、人工关节等
注射用万古霉素药物简介PPT文档共22页
谢谢你的阅读
❖ 知识就是财富 ❖ 丰富那么，任何东西都不应妨碍我沿着这条路走下去。——康德 72、家庭成为快乐的种子在外也不致成为障碍物但在旅行之际却是夜间的伴侣。——西塞罗 73、坚持意志伟大的事业需要始终不渝的精神。——伏尔泰 74、路漫漫其修道远，吾将上下而求索。——屈原 75、内外相应，言行相称。——韩非
注射用万古霉素药物简介
21、没有人陪你走一辈子，所以你要 适应孤 独，没 有人会 帮你一 辈子， 所以你 要奋斗 一生。 22、当眼泪流尽的时候，留下的应该 是坚强 。 23、要改变命运，首先改变自己。
24、勇气很有理由被当作人类德性之 首，因 为这种 德性保 证了所 有其余 的德性 。--温 斯顿． 丘吉尔 。 25、梯子的梯阶从来不是用来搁脚的 ，它只 是让人 们的脚 放上一 段时间 ，以便 让别一 只脚能 够再往 上登。
糖肽类抗生素万古霉素.精选PPT
至1982年，有报道称在 大医院中，MRSA引起的感染已 由原来的2%上升到20%。国内的研究表明，1998～ 2000年耐甲氧西林金葡菌和敏感金葡菌的比例高达30% 以上。
在这种情况下，万古霉素（国内生产的为N-去甲基万古 霉素）愈来愈引起人们的重视，是目前临床上用于治疗由 MRSA引起的严重感染疾病的首选药物，并被国际抗生素 专家誉为“人类对付顽固性耐药菌株的最后一道防线”和 “王牌抗生素”。
作用机制：
就细胞水平而言万古霉素通过干扰细菌细胞壁 的合成最终使细菌细胞发生溶解。
从分子水平上讲，万古霉素抑制细胞壁合成第二 阶段(类脂结合)中一个关键的转化反应，并在脂II 分子中通过五个氢键形成具有高度亲和力的复合 物，这些氢键从糖肽类抗生素分子的下表面与肽 聚糖末端的酰胺基和羧基结合。
万古霉素与 N-Acyl-D-Ala-D-Ala 生交互作用时的氢键
万古霉素在细胞壁 上作用位点及细胞 壁中间体发生交互 作用时的氢键
革兰阳性菌的细胞壁是由一厚厚的肽聚糖层构成，其位于 细胞质膜（内膜的外侧）；而革兰阴性菌在一薄薄的肽聚 糖层外面还有一完整的细胞外膜，可以阻止万古霉素和替 考拉宁等糖肽类抗生素渗透到肽聚糖。
因此，这类抗生素仅对革兰氏阳性菌有效。
重点用于MRSA（抗甲氧西林金黄色葡萄球菌）感染，一 般为三线用药。
万古霉素与替考拉宁的比较
重感染性疾病，临床使用很少。 （3）伴有衰弱、营养不良或无活动能力者。
这是因为静脉给药时局部疼痛和血栓静脉炎的发生率很高，以及为了避免一些输液反应如红人综合症（或称红脖综合症）的发生。 静脉给药时，万古霉素必须在溶剂稀释的条件下缓慢给药，最短给药时间为60分钟（一次总给药量大于500mg时最大给药速度小于10
万古霉素给药方案简介PPT课件
l连续腹膜透析15h以上可清除40%
一般感染患者
目标谷浓度 剂量方案 ＞10mg/L
重症感染*
15-20mg/L
常用剂量为1g q12h或 负荷剂量: 0.5g q6h（说明书） 25-30mg/kg 15-20mg/kg,q12h (实际体重)
单次剂量不超过2g，日剂 量一般不超过4g
*对于MRSA引起的严重感染，如菌血症、感染性心内膜炎、骨髓炎、脑膜 炎、医院获得性肺炎和严重皮肤软组织感染。
万古霉素吸收、分布、代谢、消除过程
吸收(生物利用度) • 腹腔注射：38% • 口服：几乎不吸收
分布 • 蛋白结合率：30%-55% • 各体液分布广泛(除脑脊液外) • 脑膜无炎症：0-4mg/L、脑膜有炎症：6.4-11.1mg/L • 表观分布容积：0.2-1.25L/kg
万古霉素吸收、分布、代谢、消除过程
万古霉素血药浓度监测
•万古霉素血药谷浓度是指导剂量调整最关键 和最实用的方法。 •Therapeutic Drug Mornitoring，TDM
–药动学原理的指导下，应用灵敏可靠的分 析技术，测定病人血液或其它体液中的药 物浓度，分析药物浓度与疗效及毒性之间 的关系，进而设计或调整给药方案
万古霉素血药浓度监测
1.5h-2h.
万古霉素概述
在输液过程中，溶液每毫升的滴数(滴／毫升)称为该 输液器的滴系数，一般记录在输液器的外包装上。 每小时输入量100ml，滴系数15滴/ml，计算 每分钟滴数=100/4=25滴
万古霉素概述
稳定性：室温保存，配置后溶液尽早使用，
若必须保存，室温或冰箱中，24小时内使
用。
•由于血液透析方式、透析时间、透 析剂量、透析器膜的特性存在差异， 药物浓度监测是指导万古霉素给药方 案及调整剂量的主要方法，尽量使血 药谷浓度维持在15mg/L以上。
万古霉素ppt课件
(三)四环素类：包括四环素、土霉素、金霉素及强力霉素等。 (四)氯霉素类：包括氯霉素、甲砜霉素等。 (五)大环内脂类：临床常用的有红霉素、白霉素、无味红霉素、乙酰螺旋霉素、麦迪霉素等、阿奇霉素。 (六)糖肽类抗生素：万古霉素、去甲万古霉素等 (七)喹诺酮类：包括诺氟沙星、氧氟沙星、环丙沙星、培氟沙星、加替沙星等。 (八)硝基咪唑类：包括甲硝唑、替硝唑、奥硝唑等。 (九)作用于G-菌的其它抗生素，如多粘菌素、磷霉素、卷霉素、环丝氨酸、利福平等。 (十)作用于G+细菌的其它抗生素，如林可霉素、氯林可霉素、杆菌肽等. (十一)抗真菌抗生素：分为棘白菌素类、多烯类、嘧啶类、作用于真菌细胞膜上麦角甾醇的抗真菌药物、烯 丙胺类、氮唑类。 (十二)抗肿瘤抗生素：如丝裂霉素、放线菌素D、博莱霉素、阿霉素等。 (十三)抗结核菌类：利福平、异烟肼、吡嗪酰胺等。 (十四)具有免疫抑制作用的抗生素如环孢霉素。
特别的是，万古霉素阻止N-乙酰胞壁酰基（NAM-）和n-乙酰葡糖酰基（NAG-）参与肽聚糖骨架的形成，而肽聚
糖骨架是革兰氏阳性菌细胞壁的主要成分。 万古霉素中大量的亲水基团可以形成氢键，与NAM-肽和NAG-肽中D-丙氨酰丙氨酸末端的部分相互作用。通常这是 一种有5个作用点的反应。这样万古霉素分子就被氢键“捆绑”在了D-丙氨酰丙氨酸上，阻止了NAM-肽与NAG-肽参 与肽聚糖骨架的形成。 万古霉素存在阻转异构现象。由于氯酪氨酸残基旋转特性的限制，万古霉素有两种典型的旋转异构体。此种构象 异构的药物具有更好的热力学稳定性，以及更高的药效。
菌内部的有用物质漏出菌体或电解质平衡失调而死。（多粘菌素和短杆菌肽）
万古霉素 PPT课件
药物代谢动力学
肾功能正常，给予500 mg多次剂量，静点30min以上
静点结束时间
平均血药浓度
0h
49 mg/L
2h
19 mg/L
6h
10 mg/L
血液平均消除半衰期为4-6小时，在最初24小时，约有75%之本品由肾小球过 滤排出，肾功能障碍者会减缓本药的排泄，全身性总清除率和肾清除率在老 年人可能会降低
可能会发生永久性或暂时性耳毒性 多数发生于用药过量 原本有失聪现象或正同时接受其他耳毒性药
物治疗者 肾功能不全的病人慎用，并应调节用药剂量
万古霉素
蒙冲
作用机制
东方链霉菌菌株
糖肽类抗生素
抑制细菌细胞壁的合成而发挥杀菌作用
主要为抑制细胞壁糖肽的合成
改变细菌细胞膜的渗透性
选择性地抑制ＲＮＡ的生物合成
不易产生耐药性，和其它抗生素之间不会 发生交叉耐药性（最近肠球菌中由质粒介 导的获得性耐药菌已引起关注）
药理作用
窄谱抗生素，对革兰氏阳性菌有效 革兰氏阳性球菌：金黄色葡萄球菌和表皮葡萄球菌（包括
特殊人群用药
老年患者用药：肾小球过滤能力会随着年龄增加而自然减 少，如不调节剂量，会引致万古霉素的血液浓度增高。
儿童用药：少儿肾脏处于发育阶段，特别是低出生体重儿、 新生儿，其血中药物半衰期延长，血药高浓度持续时间长， 所以应监测血药浓度，慎重给药。
孕妇及哺乳期妇女： FDA妊娠分级 ：C级。 C级：动物 研究证明药物对胎儿有危害性（致畸或胚胎死亡等），或 尚无设对照的妊娠妇女研究，或尚未对妊娠妇女及动物进 行研究。本类药物只有在权衡对孕妇的益处大于对胎儿的 危害之后，方可使用。
MRSA）以及链球菌（包括化脓性链球菌、肺炎链球菌、 无乳链球菌、草绿色链球菌）、棒状杆菌、梭状芽孢杆菌 （对难辨梭状芽孢杆菌高度敏感）、放线菌、链球菌属、 牛链球菌、肠球菌、类白喉菌等。 革兰氏阳性杆菌：单核细胞增多性李斯特氏菌、乳杆菌属、 放线菌属、梭状杆菌属及杆菌属。 对革兰氏阴性杆菌、分支杆菌、真菌无效 与氨基糖苷类抗生素合用对肠球菌有协同抗菌作用。
万古霉素
REVIEW ARTICLEResistance to Antibiotics:Are We in the Post-Antibiotic Era?Alfonso J.AlanisLilly Research Laboratories,Eli Lilly and Company,Indianapolis,IndianaReceived for publication June 11,2005;accepted June 23,2005(ARCMED-D-05-00223).Serious infections caused by bacteria that have become resistant to commonly used antibiotics have become a major global healthcare problem in the 21st century.They not only are more severe and require longer and more complex treatments,but they are also significantly more expensive to diagnose and to treat.Antibiotic resistance,initially a problem of the hospital setting associated with an increased number of hospital-acquired infections usually in critically ill and immunosuppressed patients,has now extended into the community causing severe infections difficult to diagnose and treat.The molecular mechanisms by which bacteria have become resistant to antibiotics are diverse and complex.Bacteria have developed resistance to all different classes of antibiotics discovered to date.The most frequent type of resistance is acquired and transmitted horizontally via the conjugation of a plasmid.In recent times new mechanisms of resistance have resulted in the simultaneous development of resistance to several antibiotic classes creating very dangerous multidrug-resistant (MDR)bacterial strains,some also known as ‘‘superbugs’’.The indiscriminate and inappropriate use of antibiotics in outpatient clinics,hospitalized patients and in the food industry is the single largest factor leading to antibiotic resistance.In recent years,the number of new antibiotics licensed for human use in different parts of the world has been lower than in the recent past.In addition,there has been less innovation in the field of antimicrobial discovery research and development.The pharmaceutical industry,large academic institutions or the government are not investing the necessary resources to produce the next generation of newer safe and effective antimicrobial drugs.In many cases,large pharmaceutical companies have terminated their anti-infective research programs altogether due to economic reasons.The potential negative consequences of all these events are relevant because they put society at risk for the spread of potentially serious MDR bacterial infections.Ó2005IMSS.Published by Elsevier Inc.Key Words:Antibiotic resistance,Bacterial resistance,New antibiotics,Antibiotic research.IntroductionIn the last 60years,major improvements in the early recognition and the treatment of infectious diseases have resulted in an extraordinary reduction in the morbidity and mortality associated with these illnesses.This has been due,in part,to our better understanding of the fine molecular biological mechanisms of these diseases and to ourimproved understanding of their pathophysiology and their epidemiology but,most notably,to the rapid development of safe and effective new antimicrobial treatments that have been able to attack the specific agent causing the infection,thus helping the infected host to eliminate the infection being treated.Seen initially as truly miraculous drugs,access to the first available systemic antibiotics (sulfonamides and penicillin)was not immediately available for the general public.In fact,these drugs were scarce and very expensive and were initially reserved for use by the military during World War II (1).As more antibiotics were discovered,manufacturing pro-cesses were simplified,and newer formulations developed,Address reprint requests to:Alfonso J.Alanis,M.D.,Vice President,Lilly Research Laboratories,Lilly Corporate Center,MC/510/07;Drop Code 6072,Indianapolis,IN 46285;E-mail:aao@Statement of potential conflict of interest:Dr.Alanis is an employee of and is an owner of shares of Eli Lilly and Company.0188-4409/05$–see front matter.Copyright Ó2005IMSS.Published by Elsevier Inc.doi:10.1016/j.arcmed.2005.06.009Archives of Medical Research 36(2005)697–705access to antibiotics eased considerably and their use became widespread.Antibiotics had truly become the‘‘panacea’’of medicine and were being used to treat even the most common and trivial types of infections,many of these non-bacterial in nature.Based on the work that he had done in his research laboratory,in an interview with The New York Times in1945, Sir Alexander Fleming warned that the inappropriate use of penicillin could lead to the selection of resistant‘‘mutant forms’’of Staphylococcus aureus that could cause more serious infections in the host or in other people that the host was in contact with and thus could pass the resistant microbe (2).He was right and within1year of the widespread use of this drug a significant number of strains of this bacterium had become resistant to penicillin.Only a few years later over50%were no longer susceptible to this new drug(2).Unfortunately,things have not improved in the recent past.In fact,every day more common and uncommon bacteria,previously susceptible to common antimicrobials, are reported to have developed resistance to different antibiotics.Although these bacteria initially caused signif-icant nosocomial infections and were the cause of major morbidity and mortality in hospitalized patients,more recently they have spread to the community,causing severe illnesses in previously healthy and otherwise non-vulnerable patients.This review tries to provide an overview of the serious problem of antibiotic resistance in the21st century and to begin to open a new window into the complex challenge of new antibiotic development in the future.For this reason, the scope of the article will focus on the problem of bacterial resistance and will not discuss viral,fungal or parasitic resistance.Excellent reviews related on the development and management of resistance of these other microorganisms can be found elsewhere(3–7). Antibiotic Resistance:A Long-Term,Serious Problem...Getting WorseIn order to befit to survive,all living organisms strive to adapt to their environment.Part of this adaptation process includes adjusting to weather conditions,to food,water and in many cases to oxygen availability and also to the presence of potentially dangerous or even lethal external agents.It is no secret that many insects have adapted remarkably well to their environment and so have micro-organisms.Thus it should not be surprising to us that bacteria have shown a remarkable ability to endure and adapt to their environment including the development of different mechanisms of resistance to most old and new antimicrobial agents.The end result of this phenomenon is that many strains of bacteria have become resistant,and in many cases multi-resistant to these therapeutic agents,thus rendering these drugs ineffective as treatments of choice for severe infections caused by these pathogens.As stated earlier,thefirst cases of antimicrobial resistance occurred in the late1930s and in the1940s, soon after the introduction of thefirst antibiotic classes, sulfonamides and mon bacteria such as strains of Staphylococcus aureus became resistant to these classes of antibiotics at record speed.For the most part,during thefirst25years after the introduction of the initial antibiotics,resistance was a problem of hospitalized patients.We learned quickly that these bacteria were not only capable of developing resistance to these antibacterial drugs but that they also could remain alive and viable in the hospital environment, thus affecting mostly vulnerable patients(especially criti-cally ill patients in the intensive care unit,those receiving steroids,the immunosuppressed,the debilitated,the chroni-cally ill and the neutropenic)who were at a higher risk and in whom eventually they caused serious nosocomial infections(8–12).The list of bacteria developing resistance is impressive, from sulfonamide and penicillin-resistant Staphylococcus aureus in the1930s and1940s(2,13)to penicillin-resistant Neisseria gonorrhoeae(PPNG),and b-lactamase-producing Haemophilus influenzae in the1970s,(14–17)methicillin-resistant Staphylococcus aureus(MRSA)and the resurgence of multi-drug resistant(MDR)Mycobacterium tuberculosis in the late1970s and1980s,(18–23)and several resistant strains of common enteric and non-enteric gram-negative bacteria such as Shigella sp.,Salmonella sp.,Vibrio cholerae, E.coli,Klebsiella pneumoniae,Acinetobacter baumanii, Pseudomonas aeruginosa,some of these associated with the use of antimicrobials in animals grown for human food consumption in the1980s and1990s(24–29).Recently we have also witnessed the report of very worrisome cases of previously unthinkable resistance as well as the spread of resistant bacteria outside the hospital causing community-acquired infections.Such is the case for strains of Group A Streptococcus becoming resistant to macrolide antibiotics(30–33),Streptococcus pneumoniae developing resistance to different antibiotic classes,in-cluding penicillin,and causing serious infections(34–41) and more virulent strains of MRSA(due to the expression of certain toxins such as the so-called Panton-Valentine leukocidin)spreading to the community(18–21,42–44),as well as Staphylococcus aureus and Enterococci becoming resistant to vancomycin(45–50).Mechanisms of Antibiotic ResistanceAt least17different classes of antibiotics have been produced to date(Table1).Unfortunately,for each one of these classes at least one mechanism of resistance(and many times more than one)has developed over the years.698Alanis/Archives of Medical Research36(2005)697–705In fact,in some cases these bacteria have been able to develop simultaneous resistance to two or more antibiotic classes,making the treatment of infections caused by these microorganisms extremely difficult,very costly and in many instances associated with high morbidity and mortality(51,52).Thus it seems that the dream that some clinicians had and the predictions that many others made in the middle of the20th century about the future eradication of most common infectious diseases from humanity will be unlikely to be achieved.If anything,recent experience with the emergence of totally new infectious diseases(AIDS,SARS, etc.),and the epidemiological trends of antibiotic resistance observed thus far,tend to indicate that we will continue to move in the opposite direction,towards an environment with an ever-growing number of new infectious diseases and of more common bacteria developing antibiotic resist-ance,more bacteria becoming resistant to several antibiotics at the same time,and some of these bacteria continuing to migrate from the hospital setting to the community. The net result could be even higher morbidity,higher mortality,higher costs,and the potential for the rapid spread of these bacteria and overall a decreasing number of useful antimicrobial agents to combat the infections they cause.Gaining a good understanding of the molecular basis for the development of resistance is important because it allows us to develop new approaches to manage the infections caused by these bacteria and to create new strategies for the development of new treatments against these bacteria.In general,it can be said that bacterial resistance has its foundation at the genetic level.This means that in most cases of bacterial resistance,changes in the genetic make-up of the previously susceptible bacteria take place,either via a mutation or by the introduction of new genetic information.The expression of these genetic changes in the cell result in changes in one or more biological mechanisms of the affected bacteria and ultimately determine the speci-fic type of resistance that the bacteria develops,resulting in a myriad of possible biological forms of resistance (51,52).Below we will review briefly both the genetic and the biological mechanisms of resistance.Genetic Mechanisms of TransmissionThe development of antibiotic resistance tends to be related to the degree of simplicity of the DNA present in the microorganism becoming resistant and to the ease with which it can acquire DNA from other microorganisms.For antibiotic resistance to develop,it is necessary that two key elements combine:the presence of an antibiotic capable of inhibiting the majority of bacteria present in a colony and a heterogeneous colony of bacteria where at least one of these bacterium carries the genetic determinant capable of expressing resistance to the antibiotic(51).Once this happens,susceptible bacteria in the colony will die whereas the resistant strains will survive.These surviving bacteria possess the genetic determinants that codify the type and intensity of resistance to be expressed by the bacterial cell.Selection of these bacteria results in the selection of these genes that can now spread and propagate to other bacteria(51).Resistance to antibiotics can be natural(intrinsic)or acquired and can be transmitted horizontally or vertically. Whereas the natural form of antibiotic resistance is caused by a spontaneous gene mutation in the lack of selective pressure due to the presence of antibiotics and is far much less common than the acquired one,it can also play a role in the development of resistance.For the most part,however,the micro-ecological pressure exerted by the presence of an antibiotic is a potent stimulus to elicit a bacterial adaptation response and is the most common cause of bacterial resistance to antibiotics(52). Susceptible bacteria can acquire resistance to antimicrobial agents by either genetic mutation or by accepting antimi-crobial resistance genes from other bacteria.The genes that codify this resistance(the‘‘resistant genes’’)are normally located in specialized fragments of DNA known as trans-posons(sections of DNA containing‘‘sticky endings’’), which allow the resistance genes to easily move from one plasmid to another(52).Some transposons may contain a special,more complex DNA fragment called‘‘integron’’,a sitecapableofintegrating different antibiotic resistance genes and thus able to confer multiple antibiotic resistance to a bacteria.Integrons have been identified in both gram-negative and gram-positive bacteria,and they seem to confer high-level multiple drug resistance to the bacteria that carry and express them(51).Table1.Major antibiotic classes by mechanism of action* Mechanism of action Antibiotic familiesInhibition of cell wall synthesis Beta-lactams(penicillins,cephalosporins, carbapenems,monobactams);glycopeptides; cyclic lipopeptides(daptomycin)Inhibition of protein synthesis Tetracyclines;aminoglycosides; oxazolidonones(linezolid);streptogramins (quinupristin-dalfopristin);ketolides; macrolides;lincosamides,Inhibition of DNAsynthesisFluoroquinolonesInhibition of RNAsynthesisRifampinCompetitive inhibitionof folic acid synthesisInhibitionSulfonamides;trimethoprimMembrane disorganizingagentsPolymyxins(Polymyxin-B,Colistin)Other mechanisms Metronidazole*Modified from Levy SB and Marshall B(51).699Antibiotic Resistance:Post-Antibiotic Era?Once a genetic mutation occurs and causes a change in the bacterial DNA,genetic material can be transferred among bacteria by several means.The most common mechanisms of genetic transfer are conjugation,transformation and transduction.Conjugation.Conjugation is the most important and the most common mechanism of transmission of resistance in bacteria.This mechanism is normally mediated by plasmids (circular fragments of DNA)that are simpler than chromosomal DNA and can replicate independently of the chromosome.The mechanism of transmission of plasmids among bacteria is via the formation of a‘‘pilus’’(a hollow tubular structure)that forms between bacteria when they are next to each other,thus connecting them temporarily and allowing the passage of these DNA fragments. Transformation.Transformation is another form of trans-mission of bacterial resistance genes and takes place when there is direct passage of free DNA(also known as ‘‘naked DNA’’)from one cell to another.The‘‘naked DNA’’usually originates from other bacteria that have died and broken apart close to the receiving bacteria.The receiving bacteria then simply introduce the free DNA into their cytoplasm and incorporate it into their own DNA. Transduction.Transduction is a third mechanism of genetic transfer and occurs via the use of a‘‘vector’’,most often viruses capable of infecting bacteria also known as ‘‘bacteriophages’’(or simply‘‘phages’’).The virus con-taining the bacterial gene that codifies antibiotic resistance (the‘‘resistant DNA’’)infects the new bacterial cell and introduces this genetic material into the receiving bacteria. Most times,the infecting bacteriophage also introduces to the receiving bacteria its own viral DNA,which then takes over the bacterial replication system forcing the cell to produce more copies of the infecting virus until the bacterial cell dies and liberates these new bacteriophages, which then go on to infect other cells.Biological Mechanisms of ResistanceWhichever way a gene is transferred to a bacterium,the development of antibiotic resistance occurs when the gene is able to express itself and produce a tangible biological effect resulting in the loss of activity of the antibiotic. These biological mechanisms are many and varied but they can be summarized as follows.Antibiotic destruction or antibiotic transformation.This destruction or transformation occurs when the bacteria produces one or more enzymes that chemically degrade or modify the antimicrobial making them inactive against the bacteria.This is a common mechanism of resistance and probably one of the oldest ones affecting several antibiotics but especially b-lactam antibiotics via the bacterial pro-duction of b-lactamases(53).Antibiotic active efflux.Antibiotic active efflux is relevant for antibiotics that act inside the bacteria and takes place when the microorganism is capable of developing an active transport mechanism that pumps the antibiotic molecules that penetrated into the cell to the outside milieu until it reaches a concentration below that necessary for the antibiotic to have antibacterial activity.This means that the efflux transport mechanism must be stronger than the influx mechanism in order to be effective(54).Efflux was first described for tetracycline and macrolide antibiotics (55,56)but is now common for many other antibiotics such asfluoroquinolones(52,54).Receptor modification.Receptor modification occurs when the intracellular target or receptor of the antibiotic drug is altered by the bacteria,resulting in the lack of binding and consequently the lack of antibacterial effect.Examples of this mechanism include modifications in the structural conformation of penicillin-binding proteins(PBPs)ob-served in certain types of penicillin resistance,ribosomal alterations that can render aminoglycosides,macrolides or tetracyclines inactive,and DNA-gyrase modifications resulting in resistance tofluoroquinolones(51,52).It is likely that more and newer biological mechanisms of resistance will develop in the future.One can only hope that as these appear,we will be able to use these new mechanisms as new targets for the development of newer, effective antibiotics.What Leads to the Development of Antibiotic Resistance?Different factors play a role in the development of antibiotic resistance but what exactly determines that some bacteria become resistant to a specific drug and not to others and what is the specific role and the‘‘relative weight’’of each one of these factors in this process remains to be defined(Table2).Our understanding of how bacteria adapt to their environment and how this process may culminate in the development of resistance against one or more antibiotics is,at best,incomplete.We are only beginning to un-derstand,at the molecular level,what steps take place for this process to occur and need to continue to gain a much better,more detailed understanding of the specific molec-ular mechanisms that serve as‘‘trigger signals’’for this process of adaptation to ultimately occur.For example,why after more than60years Group A b-Streptococcus continues to be exquisitely susceptible to penicillin but not always to erythromycin?And why other members of the Streptococcus family,such as Streptococcus pneumonia,after many decades of remaining susceptible to penicillin are now capable of presenting high-level700Alanis/Archives of Medical Research36(2005)697–705resistance to penicillin?Why after nearly30years of exhibiting high degree of susceptibility to vancomycin, Staphylococcus aureus developed resistance against this drug?Answering questions like these may help us to not only understand better thefine mechanisms that lead to bacterial resistance but also to develop strategies that result in the better design of new antibiotics that exhibit a long-term degree of activity against bacteria.In practice,however,some correlations suggest a strong association between specific patterns of antibiotic use,the type and duration of exposure,and the development of resistance.Abuse in the Use of Antibiotics in Clinical Practice Results in‘‘Selective Pressure’’The use of antibiotics in humans results in‘‘selective pressure’’in the host receiving the antibiotic.The broader the spectrum of activity,the higher chances for bacteria to develop resistance(57,58).Third-generation cephalosporins,fluoroquinolones and more recently azithromycin have been linked to these problems(58).The net result is that after the administration of the antibiotic,most susceptible bacteria in the host,the majority of which are part of the normal saprophytic bacteria colonizing that individual,are elimi-nated thus selecting only those resistant bacteria capable of surviving despite the presence of the antibiotic.The natural consequence of this selection process is that there is excessive growth of one or more resistant strains.In this way,the host becomes a reservoir of resistant bacteria that can cause an infection in this very individual or they can easily spread to other hosts causing serious infections in the most debilitated ones(59–63).It is for these reasons that antibiotics should be used very cautiously and should be prescribed only to those individuals in whom their use is clearly justified and when it clearly outweighs the potential risks,including the risk of the development of resistance.Unfortunately,in today’s healthcare system where physicians have only a few minutes to fully evaluate a patient,make a diagnosis and prescribe a treatment,and given the increasingly litigious nature of society,physicians frequentlyfind themselves under tremendous pressured to prescribe an antibiotic even when this may not be appropriate.In general,it is worth reminding the clinician that it is necessary to be far more selective and,when an antibiotic is prescribed,it should be the one with the narrower spectrum of activity.Unfortunately,the problem of antibiotic resistance has spread all around the world and in fact it is affecting poor and developing nations much harder than developed countries.This is due to the fact that antibiotics are much easier to obtain without a prescription in many of these countries whereas their access is much more limited in the developed world.The consequence of this is that poor and very poor countries face yet another challenge of immense propor-tions.They will have to educate physicians and their populations to be cautions with the use of these drugs and they will have to face the dire economic consequences of facing the problem of antibiotic resistance.This means that a significant number of people will likely die in these poor nations because their health services will not be able to afford the level of sophistication and expenditure that their complex infectious diseases require.It also means that it is quite likely that in these countries the spread of community-acquired infections due to multi-resistant microorganisms will be broad and will likely serve as the reservoir from which these bacteria will migrate to other regions. Agricultural and Animal Use of Antibiotics Antibiotics are frequently used in animals as part of the process used to manufacture food,especially meats.This is a non-therapeutic use of very valuable drugs and for this reason they should be preserved for use under very special circumstance only(28,29).Recent interactions between regulatory authorities and the food-producing industry in the U.S.are resulting in commitments to reduce and eventually eliminate the use of common antibiotics for non-therapeutic use.Looking at the Future:Is This the Post-Antibiotic Era? The problem of the explosive growth in the development of antimicrobial resistance in the last two decades has only been made worse by a significant and steady decrease in the number of approvals of new antibacterials in the last10–15 years(Figure1)(64).The different forces contributing to this major paucity in the pace of antibiotic innovation are multiple,very complex and interlinked,and much has been written about these inTable2.Risk factors for the development of antibiotic resistance Practices associated with the development of antibiotic resistance Excessive and irrational over-utilization of antibiotics in outpatient practice and in hospitalized patients,either therapeutically or prophylacticallyUse of antibiotics in agricultural industry,particularly in the production of foodLonger survival of severely ill patientsLonger life expectancy with increased use of antibiotics in the elderly. Advances in medical science have resulted in the survival of many patients with severe illness and at risk for infections:Critically ill patientsImmunosuppressionCongenital diseases(i.e.,cysticfibrosis)Lack of use of proven and effective preventive infection control measures such as hand washing,antibiotic usage restrictions and properisolation of patients with resistant infectionsIncreased use of invasive proceduresIncreased use of prosthetic devices and foreign bodies amenable to super infection with resistant bacteria 701Antibiotic Resistance:Post-Antibiotic Era?recent times (64–73).When analyzed individually,these forces seem to have merit on their own weight but they do not appear to be insurmountable.However,when com-bined,they seem to have had a multiplier effect that has now resulted in the creation of a crisis of major proportions which some predict may have unforeseen and dramatic consequences (65).Some of these key obstacles are explained as follows.Tradeoffs Have Been Made within Anti-Infectives Therapeutic ClassThe emergence of new,life-threatening infectious diseases,especially AIDS,has created significant and unexpected needs for the discovery and development of new safe and effective anti-HIV drugs that are capable of prolonging and improving the life of those infected with the virus and of containing the spread of this global disease.Research in this area has taken place in record time and new targets have been unfolded quite rapidly.The result of this has been the discovery and the development of a significant number of truly life-saving antiretroviral agents that when used in appropriate combinations to treat patients suffering from AIDS are literally able to keep these patients alive for years and to resume as normal a life as possible.These successes,however,have created significant internal pressure within pharmaceutical companies since these normally develop their R &D budgets by Therapeutic Area.This means that in most companies that have a Division of Infectious Diseases,the budget for anti-infectives is limited (as is the budget for other therapeutic groups),and in recent years a significant amount of the anti-infective investments made in the industry have been directed to new antiretroviral agents at the expense of other antimicrobials,especially antibiotics.To illustrate this point one only needs to see what has happened in the U.S.in recent years in the field of anti-infectives.From 1998to 2003only nine antibacterials were approved in the U.S.by the Food and Drug Administration(FDA)and of these only two (Daptomycin and Linezolid)had truly novel mechanisms of action.During the same time,nine anti-HIV agents were approved,four of these in 2003alone.Thus,from 1998to 2003the number of antibacterials developed by large pharmaceutical compa-nies and approved in the U.S.by the FDA was the same than the number of new anti-HIV drugs made available to patients with AIDS (64).Antibacterial research productivity has been lower than expected and there has been higher attrition in the pipeline of new antibiotics.Simply speaking,the new technologies such as genomic research,combinatorial chemistry and throughput screening,once heralded as capable of yielding a large number of novel targets amenable to modulation via their interaction with new drugs,have thus far failed to deliver on their promise in the field of antibacterial discovery and research (65).The consequence of this is that no new antibiotic classes have been discovered through the use of these new techniques and thus we continue to face the same barrier than before,the need for new antibacterial platforms for the delivery of new products (65).Additionally,my observation is that in the last decade,the pharmaceutical industry has stopped the development of a significant number of new antibacterial molecules at different stages of progress because these did not meet their expectations due to a wide variety of reasons including manufacturing problems,safety concerns,lower efficacy than expected,or simply due to economic considerations.The result is that the development of these drugs was terminated,thus reducing the overall number of molecules in the antibiotic pipeline.Iterations over ‘‘traditional’’antibacterial chemical structures have been nearly exhausted.It is extremely unlikely,if not impossible,that incremental change that produces new iterations over these old chemical structures will yield the innovative,safe and effective new antibiotics that society needs.The field of antibacterial research is literally ‘‘crying’’for transformational change.This means that in order to produce radically different and novel antimicrobials,we need to be capable of approaching the problem with a fresh and different view which results in truly innovative ‘‘platforms,’’totally unrelated to the old ones.Only experimenting with new targets,new bacterial biological processes and new mechanisms of action we will be able to produce the next new classes of antibiotics,with the desired potency,the right spectrum of activity,the expected therapeutic effect and a clean safety profile,capable of withstand the threat of multi-resistant bacteria.However,as we have learned from other therapeutic areas such as neurosciences,oncology or cardiovascular diseases in recent years,we need to understand that the creation of these novel platforms will be far more resource intensive,far more expensive and it will take a significantly longer time to be developed than those needed forthe24681012141618N o . N e w A n t i b a c t e r i a l A g e n t sFigure 1.New antibacterial agents approved by the FDA in the U.S from 1983to 2003.Data from Reference 70.702Alanis /Archives of Medical Research 36(2005)697–705。
万古霉素(课件)
– 有脑膜炎时，能渗透进入脑脊液
•
半衰期：
– 肾功能正常患者为 4 ～6 小时 – 肾功能衰竭的患者半衰期为 7.5 天
稳可信的药代动力学
• 蛋白结合率为 55％ • 代谢
– 稳可信在体内很少被代谢 – 静脉给药后，多以原型经肾脏排出 – 静滴後24小时，尿排泄率为80% - 90%
•
血透及腹透均不能清除本品
万古霉素预防性应用
• MRSA分离率高的医疗机构预防MRSA感染 – 神经外科手术 – 骨科大手术 – 预防导管感染 – 心血管外科手术 • 万古霉素预防感染的效果存在争议
稳可信的药代动力学
• • 给药方式：
– 静脉滴注（口服不易吸收）
吸收与分布：
– 1g静滴後2小时，血中浓度25µg/ml （* 0.5-4 µg/ml 的浓度能抑制多数敏感菌株） – 本品能渗透进入骨髓、骨组织、关节液和腹水 – 能通过胎盘进入胎儿体内
稳可信的作用机制
稳可信属快效杀菌剂 杀菌剂 稳可信具有三重 三重作用机制 三重 • 抑制细菌细胞壁的合成
抑制细菌细胞壁粘肽链合成的第二步 与五肽末端氨基酸分子结合，阻断转肽交叉连接 转糖作用发生障碍
• •
• 影响细菌细胞膜的通透性 • 抑制细菌孢浆中RNA的合成
稳可信 － 独特的抗菌作用机制
稳可信(层析纯化)：
* MRS对所有b-内酰胺类抗生素耐药，但对稳可信敏感 MRS对所有b
3 临床应用
稳可信的适应症
• 本品适用于耐甲氧西林金黄色葡萄球菌(MRSA) 及其他细菌所致的感染：
• • • • • • • • • • 败血症 感染性心内膜炎 骨髓炎 关节炎 灼伤、手术创伤等浅表性继发感染 肺炎 肺脓肿 脓胸 腹膜炎 脑膜炎
- 1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。
MRSA是临床重点监测的多重耐药菌种之一
2004-2006年美国ZAPPS/LEADER监测项目结果显示1-5
60%
54.2% 56.6%
50%
40%
34.2% 33.1%
20%
MRSA分离率(%)
0%
2004 2005 2006(年)
ZAPPS
2004 2006 (年) LEADER
1.
Jones
MSSA
29%
40 30.2
26.5 30
20
百分比(%) 天数
20
15%
10
P=0.00
0
1
28天
死亡率
P=0.01
住院 死亡率
9.7
6.4 P=0.04 机械通气 减少天数
10
0 ICU 住院天数
* VAP：呼吸机相关肺炎
6
Combes A.et al. Am J Respir Crit Care Med Vol.2004;170:786-792
11
Chemother. 2007;60:788-94
金葡菌对万古霉素MIC越高，治疗成功率越低
1.0≤ MIC≤2µg/mL，万古霉素的治疗MRSA菌血症成功率差别极为悬殊
60%
55.6%
治疗成功率(%)
40%
46.1%
20%
P=0.01
9.5%
n=9
0%
n=21
MIC≤0.5
1.0≤ MIC ≤ 2.0 (µg/mL)
RN
et
al.
J
Antimicrob
Chemother.
2006;57:279-87；2.
Ross
JE
4
et al.
Int
MRSA是导致肺部感染患者死亡的 最主要原因之一
MRSA感染死亡率(%)
MRSA导致肺部感染患者死亡率达40％左右
60% 45%
44%
38%
30%
15%
0%
28/64
院 内 M R S A 肺 部 感 染1
2002-03-04年 2004年总用量
10
MRSA对万古霉素的MIC值高漂
百分比(%) 既往CLSI标准2
100
90
2001
2003
2005(年)
80
70
60
50
40
30
20
10
0
0.125 0.19 0.25 0.38 0.5 0.75 1 1.5 2 3 4 万古霉素MIC1(mg/L)
1.Steinkraus G et al. J Antimicrob
100 90
2001
2003
2005(年)
80
70
60
50
40
30
20
10
0
0.125 0.19 0.25 0.38 0.5 0.75 1 1.5 万古霉素MIC(mg/L)
为了保证 治疗风险 性降到最 低，将万 古霉素 2 M3IC值予4 以调整
Steinkraus G et al. J Antimicrob Chemother.
12/32 MRSA肺炎2
1.吴本权等.中国结核和呼吸杂
志.2000.23(7):413-416
5
2 .Wahara T et al. Chest 1994;105:826–
MRSA感染导致VAP*患者病情加重
MRSA感染导致VAP患者死亡率增加，治疗时间延长
60
50
40 32%
30
MRSA 49%
13
2007;60:788-94
万古霉素属于时间依赖性抗菌药，AUC/MIC是与疗效密切相关的PK/PD*参数1
*PK：药代动力学；PD：药效动力学
汪复等。实用抗感染治疗学。2005版
14
万古霉素AUC/MIC比值越高，疗效越佳
治疗成功率(%)
100% 80%
治疗呼吸道感染，万古霉素 AUC24/MIC >345时，疗效更佳
9
全球万古霉素使用量逐年增加
世界每年万古霉素的需求量总计约20～25吨
• 美国每百万张病床万古霉素使用量为
8.0吨
100
• 35%用于预防
• 32%用于经验治疗
• 33%用于感染症治疗
• 我国临床广泛使用的糖肽类抗生素主 要有
• 万古霉素
• 去甲万古霉素
• 替考拉宁
0我国糖肽类药物使用量逐年加 95万支15万古霉素AUC/MIC比值越高，疗效越佳
治疗金葡菌肺炎，万古霉素 AUC24/MIC >400时，细菌培养阳性率更低 100
细菌培养阳性率(%)
80
AUC24/MIC＜400(n=16)
60
AUC24/MIC≥400(n=18)
40
20
0
10
20
30
治疗时间 (天数)
一项对160例金葡菌所致下呼吸道感染患者静脉滴注万古霉素，评价万古霉 16 素MoAiUseC-/BMrIoCd与er临P床A疗et效a关l. C系li的n 研Ph究armacokinet.
78%
60%
40% 20%
24%
(n=21) 0%
AUC/MIC≤345
(n=32) AUC/MIC >345
一项对70例下呼吸道感染患者静脉滴注万古霉素，进行剂量调整达到血药浓度
M在o1i0s-e30PmAge/tmaLl.，A评m价J 万He古al霉th素SAysUtCP/hMaICrm与. 临20床00疗1效5;关:S系4-的研究
n=1551 n=2546
n=4744 n=1839
耐氟喹诺酮 耐3代头孢菌素耐甲氧西林金葡耐菌万古霉素肠耐球亚菌胺培南
铜绿假单胞菌 大肠埃希菌
铜绿假单胞菌
* 耐药菌株增长百分比
3
National Nosocomial Infections Surveillance (NNIS) System
MRSA临床分离率日益升高
治疗MRSA感染的挑战及机会 金葡菌对万古霉素MIC
1
MRSA*流行病学现状及其危害
*MRSA：耐甲氧西林金黄色葡萄球菌
2
近年来临床耐药菌株检出率增长迅速
1999年与1994-98年相比， ICU中耐药菌株检出率明显增高
60%
49%
48%
40%
40%
40%
20%
20%
增长率*(%)
0% n=2657
S一ak项ou自la1s99G8年et7a月l. 至Jo2u0r0n1a年l o1f1C月li，ni对ca3l 0M例ic菌ro血bi症og进og行y的. 回顾性分析研究结果显示
2004;42:2398-2402
12
金葡菌对万古霉素敏感折点调整≤2ug/mL
百分比(%) 2006年CLSI标准
既往CLSI标准
治疗MRSA感染的现状及挑战
7
1996年
ATS指南推荐MRSA感染治疗策略
万古霉素是治疗MRSA感染的唯一选择
致病菌
抗菌药选择
厌氧菌 MRSA 军团杆菌属
克林霉素 万古霉素 红霉素＋/－利福平
Am J Respir Crit Care Med. 1996;153:1711-25
8
万古霉素使用量增加，导致金葡菌对万古霉素MIC值升高，临床治疗失败率 增高