重症患者侵袭性真菌感染诊断与治疗指南(2007)

重症患者侵袭性真菌感染诊断与治疗(2007) 重症患者侵蒃性菌感染蒃治蒃指南真断与;2007, 中蒃重症分医学会医学会 通信作者: 150086 哈蒃蒃科大附第二院;医学属医于蒃江,,主任蒃～医 Email: drkaijiang@sohu.com ICU患者是侵蒃性菌感染真(invasive fungal infections, IFI)的高蒃人群～且IFI正成蒃蒃致ICU患者死亡的重要病因之一。前～外有些者把当国内学IFI蒃侵蒃性菌病;称真invasive fungal disease,IFD,,蒃此有蒃。蒃使重症工作者蒃尚争医学IFI有一全面、系蒃的蒃蒃～中蒃个医学会 重症分蒃蒃相蒃蒃家～依据近年外究蒃展和蒃床蒃～制定了重症患者侵蒃性菌医学会来国内研践真 感染蒃和治蒃指南～旨在指蒃蒃范我断与国ICU生的蒃床蒃蒃蒃工作。医医践 一、ICU患者IFI的流行病学 1,ICU患者IFI的蒃病率,在蒃去的十年中几ICU患者IFI的蒃病率不升高～蒃占院蒃得断医 性感染的8,,15%。以念珠菌蒃主的酵母蒃菌和以曲蒃主的蒃菌是真霉状真IFI最常蒃的病原菌～分蒃占91.4%和5.9%。在美～国念珠菌血症已蒃居院血源性感染的第内4位。究蒃示～研器官移植受者菌感染的蒃病率蒃真20%,40%～而AIDS患者蒃生菌感染的可能性高真达90%。管抗菌尽真的非蒃物治蒃措施越越受到重蒃～且不有新的抗菌蒃物蒃世～但来断真IFI的蒃病率仍呈明蒃上升蒃蒃。 2,ICU患者IFI的重要病原菌,ICU患者IFI的病原菌主要包括念珠菌和曲。霉ICU患者IFI仍以念珠菌蒃主～其中白念珠菌是最常蒃的病原菌(占40%,60%)。但近年非白念珠菌来(如光滑念珠菌、蒃蒃念珠菌、近平滑念珠菌等)感染的比例在逐蒃增加。 侵蒃性曲感染的蒃生率亦在逐蒃上升霉,占所有IFI的5.9%,12%。曲多存在于潮蒃暗且霉湿 缺乏通蒃的蒃境中～其蒃子蒃浮于空中易被患者吸入。曲气霉属中最常蒃的是烟曲、曲及黑霉黄霉曲～焦曲土曲蒃少蒃。霉霉与霉另外～蒃多蒃、蒃蒃、接合菌中的根毛的感染率霉属霉属霉属与霉属 亦有所升高。 3,ICU患者IFI的病死率,ICU患者IFI的病死率高～很蒃次于血液系蒃蒃瘤患者。 侵蒃性念珠菌感染的病死率达30%,60%～而念珠菌血症的粗病死率甚至高达40%,75%～其中光滑念珠菌和蒃蒃念珠菌感染的病死率明蒃高于白念珠菌等其他念珠菌。 尽管ICU患者侵蒃性曲感染蒃生率低～但其病死率高～是免疫功能抑制患者死亡的主霉 要原因。 4,ICU患者IFI的高危因素,在ICU 中～IFI除了可蒃生于存在免疫抑制基蒃疾病或接受免疫抑制治蒃的患者外～更多的蒃是蒃生于之前无免疫抑制基蒃疾病的重症患者～蒃疾病本与身或治蒃等因素蒃致的免疫麻痹/免疫功能紊乱有蒃。 与其他科室的患者相比～ICU患者最突出的特点是其解剖生理障完整屏坏性的破。ICU患者往往蒃有多蒃体内插黏腔和血管的管～且消化道蒃以正常利用～蒃其他患者具有更多的皮蒃、膜等解剖生理障屏体体黏条真蒃害～故使得正常定植于皮蒃和腔膜表面的件致病菌以及蒃境中的菌易于侵入原本无菌的真与深部蒃蒃血液。 ICU患者IFI的高危因素主要包括,;1,ICU患者病情危重且蒃蒃～;2,侵入性蒃蒃治与蒃手段的广泛蒃用～;3,蒃用广蒃抗菌蒃物～;4,常合并糖尿病、慢性阻塞性肺疾病、蒃瘤等基蒃疾病～;5,蒃固醇激素免疫抑制蒃在蒃床上的与广泛蒃用～;6,器官移植的广泛蒃展～;7,蒃 瘤化蒃/放蒃、HIV感染等蒃致患者免疫功能低下～;8,随着ICU蒃治水平的不断提高～使重症患者生存蒃蒃与住ICU的蒃蒃延蒃。 二、IFI常蒃病原菌的真特点 引起IFI的病原可分蒃蒃,性致病菌体两真与条数件致病菌。前者蒃由少致病菌蒃成～主要包括蒃蒃胞蒃菌与它球蒃子菌～蒃可侵入正常宿主～也常在免疫功能低下的患者中引起疾病。在免疫功能受蒃的患者中～由真条性致病菌所致的感染常蒃致命性的。件致病菌主要包括念珠菌与霉霉霉曲～多侵犯免疫功能受蒃的宿主。念珠菌、曲、蒃球菌、毛是最常蒃的引起IFI的病原菌。 1,致病性念珠菌,念珠菌是最常蒃的一蒃条件致病菌～常蒃的致病性念珠菌;假蒃酵母菌,有,白念珠菌、蒃蒃念珠菌、近平滑念珠菌、光滑念珠菌、克柔念珠菌、季也蒙念珠菌、葡萄牙念珠菌。 念珠菌培蒃蒃生酵母蒃菌落。蒃微蒃下～除光滑念珠菌外～大部分念珠菌在玉米吐温蒃脂培蒃基上均可蒃生假菌蒃及芽蒃～白念珠菌蒃可蒃生厚膜蒃子。在37?血中清培蒃2,3h～可蒃出芽管～是重要的蒃蒃室蒃蒃特征。 念珠菌广体体泛存在于自然界中～大多无致病性。作蒃人的正常菌群～只有在机防御机制受蒃蒃才会决与黏致病。其毒力由多蒃因素定～包括念珠菌蒃蒃的附性、念珠菌酵母相-菌蒃相的双与体相性等～同蒃念珠菌感染机防御功能密切相蒃。 2,致病性曲霉,曲蒃霉条霉霉黄霉件致病菌～致病性曲的蒃群主要包括烟曲、曲蒃和土曲霉霉学划等。曲的蒃定主要依蒃形蒃特征,通常以菌落形蒃和分生蒃子蒃的蒃色蒃行群的分～然后以分生蒃子的形蒃和蒃色、蒃蒃蒃的构数条目、蒃囊的形蒃以及有性蒃子的形蒃等蒃行蒃的蒃定。培蒃件蒃蒃准化～常用的培蒃基蒃察氏蒃脂或察氏酵母浸膏蒃脂。 曲蒃子蒃霉2,5μm大小～易在空中蒃浮。吸入蒃子气霉后可引起曲病～肺和鼻蒃最易受累～依据宿主的免疫蒃可蒃生多蒃不状个体霉同的蒃床蒃型。蒃免疫功能正常的～曲可成蒃蒃敏原或引起肺或鼻蒃的限局性感染～蒃免疫功能蒃重受蒃者～曲可在霉体肺或鼻蒃蒃大量生蒃～然后播散至身其他器官。 3,致病性蒃球菌,蒃球菌中新生蒃属它两个即球菌是最常蒃的致病菌～包括蒃蒃～新生蒃球菌新生蒃蒃和格特蒃蒃～前者广几泛分布于世界各地～常存在于蒃蒃等蒃蒃的排泄物中～乎所有的AIDS患者蒃的蒃并区从离球菌感染均是由蒃蒃蒃引起～后者主要分布于蒃蒃、蒃蒃蒃地～可蒃蒃中分到。 新生蒃球菌培蒃蒃生奶径油色酵母蒃菌落～蒃微蒃下可蒃球形或蒃蒃形酵母蒃胞～直2,5μm～第一代培蒃物有蒃可蒃小的蒃膜。蒃脊液直接涂片可蒃蒃球菌的酵母蒃胞有蒃蒃的蒃膜。 健康人蒃蒃菌有免疫力,只有当体体机抵抗力下降蒃～病原菌才易侵入人致病。蒃菌最常侵 犯中枢径神蒃系蒃～也可引起蒃重的肺部病蒃～其主要感染途蒃呼吸道。蒃球菌病好蒃于AIDS、糖尿病、蒃期蒃瘤、系蒃性蒃斑狼蒃、器官移植等患者。 4,相菌,双真双真体相菌是指在人和37?件下条蒃生酵母相～而在27?件下条蒃生菌蒃相的一蒃菌～蒃原蒃性病原菌。主要包括真真青霉申克蒃子蒃菌、蒃蒃尼菲、蒃膜蒃蒃胞蒃菌、粗球蒃子菌、副球蒃子菌、皮炎芽生菌。除蒃子蒃菌病多蒃皮蒃外蒃后感染外～其他菌主要真由呼吸道感染～但蒃大多感染者无症～蒃数状数自限性疾病～少患者可蒃展蒃蒃重的系蒃性蒃害。 5,致病性接合菌,接合菌蒃包括毛霉与虫霉霉霉目目～其中毛目的致病菌主要包括毛、根、根毛和霉霉霉虫霉霉与霉虫叮犁蒃～目的致病菌有蛙蒃耳～主要通蒃微小外蒃和昆咬而感染。 接合菌可引起接合菌病。毛霉称霉目所致感染最蒃常蒃～又毛病～其蒃病有多蒃易感因素～如高血糖、代蒃性酸中毒、大蒃量蒃用蒃固醇激素、白蒃胞减数气少等～大多患者通蒃吸入空中的毛霉与蒃子而感染～其次是食入或外蒃致病～肺鼻蒃最常受累。 6,卡氏肺蒃子菌,卡称卡虫氏肺蒃子菌主要引起肺部感染～蒃氏肺蒃子蒃肺炎;pneumocystis carinii pneumonitis～PCP,～主要蒃于AIDS免疫功能受蒃者。与 蒃于卡迄争来学研卡与真氏肺蒃子菌的分蒃今仍有蒃。近年分子生物究蒃示～氏肺蒃子菌菌有60%的相似性, 而原与虫只有20%的相似性～故支持氏肺卡真尚蒃子菌蒃菌的蒃点。蒃菌目前不能在外体靠涂胺断培蒃蒃得～主要依直接片六蒃染色蒃。PCR技蒃可作蒃蒃助蒃断手段。 三、IFI的定蒃 IFI系指菌侵入人蒃蒃、血液～在其中生蒃真体并繁殖引致蒃蒃蒃害、器官功能障碍、炎症反蒃的病理改蒃及病理生理蒃程。蒃于重症患者IFI的定蒃目前无蒃一定蒃～危蒃;尚宿主,因素、蒃床特征、微生物蒃蒃成了此定蒃的基蒃。构 四、重症患者IFI的蒃断 重症患者IFI的蒃分断3蒃蒃,蒃、蒃床蒃、蒃蒃。个确断 IFI的蒃一断学学般由危蒃;宿主,因素、蒃床特征、微生物蒃蒃、蒃蒃病理4部分蒃成。蒃蒃病理学仍是蒃的断金蒃准。 ;一,蒃确, 1,深部蒃蒃感染,正常本蒃无菌的深部蒃蒃蒃活蒃或尸蒃蒃蒃有菌侵入性感染的蒃蒃蒃据～或真学 除泌尿系、呼吸道、副鼻蒃外正常无菌的封蒃体腔/器官中蒃蒃菌感染的真学微生物蒃据;培蒃或特殊染色,。 2,菌血症,真血液菌真阳并状培蒃性～排除蒃染～同蒃存在符合相蒃致病菌感染的蒃床症与体征。 3,蒃管相蒃性菌血症,蒃于真静脉体当深留置的蒃管行外培蒃～蒃管尖;蒃度5cm,半定量 2 培蒃菌落蒃数>15CFU/ml,或定量培蒃菌落蒃数,10CFU/ml～且外与并周血培蒃蒃同一致病菌～除外其他部位的感染可蒃。确若蒃隧道式或抗感染蒃管～有其特殊的定蒃,可蒃相蒃的蒃管相蒃性参感染指南。 ;二,蒃床蒃断 至少具有1蒃危蒃;宿主,因素～具有可能感染部位的1蒃主要蒃床特征或2蒃次要蒃床特征～并同蒃具蒃至少1蒃微生物蒃蒃蒃学阳果性。 ;三,蒃蒃 至少具有1蒃危蒃;宿主,因素～具蒃1蒃微生物蒃蒃蒃学阳果性～或者具有可能感染部位的1蒃主要蒃床特征或2蒃次要蒃床特征。 ;四,蒃断IFI的参照蒃准 1,危蒃;宿主,因素, ;1,无免疫功能抑制的患者～蒃抗生素治蒃72,96h仍有蒃蒃等感染征象～蒃并条足下列件之一的蒃高危人群。 ?患者因素, I,老年;年蒃,65蒃,、蒃蒃不良、肝硬化、胰腺炎、糖尿病、慢性阻塞性肺疾病等肺部疾病、蒃功能不全、蒃重蒃蒃/蒃蒃伴皮蒃缺蒃、蒃功能减痹退或蒃麻等。 II,存在念珠菌定植～尤其是多部位定植;指同蒃在2或个2以上个离真即部位分出菌～使菌株不同,或某一部位持蒃定植;指每周至少有2次非蒃蒃部位的培蒃呈性,。阳 若有条件～高危患者每周2次蒃蒃包括胃液、气道分泌物、尿、口咽拭子、直蒃拭子5个部位的蒃本蒃行定量培蒃～蒃算阳当数性蒃本所占的比例。定植指;CI,?0.4或校正定植指数;CCI,?0.5蒃有意蒃。CI的蒃蒃蒃,断口咽/直蒃拭子蒃本培蒃CI?1 CFU/ml～胃液/尿 242 CI?10CFU/ml～痰CI?10CFU/ml～CCI的蒃蒃蒃,断口咽/直蒃拭子蒃本培蒃CCI?10 5 CFU/ml～胃液/尿/痰CCI?10CFU/ml。 ?治蒃相蒃性因素, I.各蒃侵入性操作,机械通气>48h、留置血管蒃管、内气插留置尿管、管管/气管切蒃、包括腹膜透析在的血液蒃内化治蒃等。 II,蒃物治蒃,蒃蒃蒃使用3蒃或3蒃以上抗菌蒃物;尤其是蒃抗生素,、多成分蒃血、全广胃蒃外蒃蒃、任何蒃量的激素治蒃等。 III,高危腹部外科手蒃,消化道穿孔>24h、反蒃穿孔、存在消化道蒃、腹壁切口裂蒃、有可能蒃致蒃壁完整性蒃生破坏的手蒃及急蒃再次腹腔手蒃等。 ;2,存在免疫功能抑制的患者;如血液系蒃蒃性蒃瘤、HIV感染、骨髓移植/异基因造血干蒃胞移植、存在移植物抗宿主病等,～当体温出蒃>38?或<36?～蒃足下述件条之一的蒃高危人群。 ?存在免疫功能抑制的蒃据～具蒃下述情况之一, 9/L,且持蒃10d以上～I.中性粒蒃胞缺乏;<0.5×10 II,之前60d内并出蒃蒃中性粒蒃胞缺乏超蒃10d～ III,之前30d接受蒃或正在接受免疫抑制治蒃或内放蒃;口服免疫抑制蒃>2周或静脉化蒃>2个蒃程,～ -1-1IV,蒃期蒃用糖皮蒃激素;或静脉当口服相于蒃尼松0.5mg?kg重体?d以上>2周,。 ?高危的蒃器官移植受者,体 I,肝移植伴有下列危蒃因素,再次移植、蒃中大量蒃血、移植后早期;3d,内真出蒃菌定植、蒃蒃的手蒃蒃蒃、蒃功能不全、移植后蒃蒃蒃菌感染等。 II,心蒃移植伴有下列危蒃因素,再次手蒃、巨蒃胞病毒;CMV,感染、移植后需要透析、病区在2个内霉月曾有其他患者蒃生侵蒃性曲感染等。 III,蒃移植伴有下列危蒃因素:年蒃,40蒃、糖尿病、CMV感染、移植后伴蒃菌感染、蒃后出蒃中性粒蒃胞减少症等。 IV,肺移植伴有下列危蒃因素,蒃前曲霉气并支管定植、合呼吸道蒃菌感染、CMV感染、蒃固醇激素治蒃等。 ?蒃足上述无免疫功能抑制的有基蒃疾病患者中所述的任意一危蒃因素。条 2,蒃床特征 ;1,主要特征,存在相蒃部位感染的特殊影像改学蒃的蒃据。 如侵蒃性肺曲感染的霉学影像特征包括,早期胸膜下密度增高的蒃蒃蒃蒃影～光蒃征;halo sign,～新月形空气征(air-crescent sign)～蒃蒃区内学域出蒃空腔等。是否出蒃上述典型影像特征～取决体状于基蒃疾病的蒃蒃、病程所蒃的蒃段、机的免疫蒃～ICU中大部分无免疫功能抑制的患者可无上述典型的影像表学蒃。 ;2,次要特征,蒃足下述可疑感染部位的相蒃症、状体征、至少1蒃支持感染的蒃蒃室蒃据;常蒃或生化蒃蒃,3蒃中的2蒃, ?呼吸系蒃,近期有呼吸道感染症或状体咯征加重的表蒃;咳嗽、咳痰、胸痛、血、呼吸困蒃听内湿学蒃蒃及肺蒃音等,～呼吸道分泌物蒃蒃提示有感染或影像出蒃新的、非上述典型的肺部浸蒃影。 ?腹腔,具有弥漫性/局灶状体异性腹膜炎的症或征;如腹痛、腹蒃、腹蒃、肌蒃蒃、蒃功能常 等,～可有或无全身感染表蒃～腹腔引流管、腹膜透析管或腹腔穿刺液蒃本生化或常蒃蒃蒃常。异 ?泌尿系蒃,具有尿蒃、尿急或尿痛等尿路刺激症～状触区体下腹痛或蒃叩蒃痛等征～可有或无全身感染表蒃～尿液生化蒃蒃及尿沉数异渣蒃胞常(男性WBC>5个/HP,女性>10个/HP,～蒃于留置尿管超蒃7d的患者～有上当状体并状述症或征蒃蒃尿液中有絮蒃蒃蒃物漂浮或沉于尿袋蒃亦蒃考蒃。 ?中枢枢灶状体异神蒃系蒃,具有中神蒃系蒃局性症或征;如精神常、蒃蒃、偏蒃、蒃膜刺激征等,～蒃脊液蒃蒃示生化或蒃胞数异体常～未蒃病原及蒃性蒃胞。 ?血源性,当异声出蒃眼底常、心蒃超提示瓣膜蒃生物、皮下蒃蒃等表蒃而血培蒃蒃性蒃～蒃床能除外其他的感染部位～亦要高度蒃疑存在血源性菌感染。真 3.微生物蒃蒃,所有蒃本蒃蒃新蒃、合学真涂格蒃本。其蒃蒃手段包括蒃蒃的菌片、培蒃技蒃以及新近的基于非培蒃的蒃断技蒃。包括,(1)血液、胸腹水等无菌液蒃体阳球菌抗原性～(2)血液、胸腹水等无菌液体学真确直接蒃蒃或蒃胞蒃蒃蒃蒃除蒃球菌外的其他菌;蒃蒃蒃蒃蒃球菌可蒃,～(3)在未留置尿管的情下况～蒃蒃2份阳尿蒃培蒃呈酵母菌性或尿蒃蒃念珠菌管型～(4)直接蒃尿蒃蒃得的尿蒃培蒃呈 5酵母菌性;阳尿念珠菌>10CFU/ml,～(5)更蒃尿管前后的2份阳尿蒃培蒃呈酵母菌性;尿念 5珠菌>10 CFU/ml,～(6)气道分泌物[包括蒃口、管管、气插气支管肺泡灌洗、保蒃性蒃本刷;PSB,等手段蒃取的蒃本]直接蒃蒃/蒃胞学蒃蒃蒃蒃菌蒃/蒃子或菌真阳培蒃性～(7)蒃胸、腹、盆腔引流管/腹膜透析管等留取的引流液直接蒃蒃/蒃胞学蒃蒃蒃蒃菌蒃/蒃子或菌真阳培蒃性～(8)蒃蒃室引流管留取的蒃本直接蒃蒃/蒃胞学蒃蒃蒃蒃菌蒃/蒃子或培蒃性～阳(9)血液蒃本半乳甘露聚糖抗原;GM,或β-1～3-D葡聚糖;G蒃蒃,蒃蒃蒃蒃2次性。阳 五、重症患者IFI的蒃防 1,一般蒃防,蒃治蒃原蒃病～可能极尽屏减保蒃解剖生理障～少不必要的侵入性操作。已存在解剖生理障屏极并尽屏尽蒃蒃或蒃行了必要的有蒃操作后～蒃注意蒃保蒃早恢蒃障的完整性。如早拔除留置的蒃管～蒃短静脉内蒃蒃的蒃用蒃蒃～早日蒃蒃蒃蒃蒃等～蒃有免疫功能抑制的患者～需促蒃免疫功能的恢蒃。 加强蒃ICU蒃境的蒃控～蒃行分管区离离理～建立隔病房。蒃格蒃行消毒隔、无菌技蒃操作蒃程、探蒃制度及洗手制度等～少减几交叉感染的率。蒃病房、蒃器、管路等蒃行定期蒃格的消毒～尽减并尚可能少灰蒃～避免蒃水存留～加强病房的通蒃。此外～需蒃蒃人蒃及患者家加医属强蒃生宣教医真当状况力度～蒃展院感染蒃控～了解侵蒃性菌在地的病蒃及其流行。 推荐意蒃1,蒃防IFI首先要治蒃原蒃病～可能尽并屏保蒃早期恢蒃解剖生理障 (推荐蒃蒃蒃E蒃) 推荐意蒃2,蒃防IFI需加强蒃ICU蒃境的蒃控 (推荐蒃蒃蒃E蒃) 2,靶向蒃防,蒃存在免疫功能抑制的患者～蒃防用蒃可少其减真尿路菌感染的蒃生～同蒃呼吸道真真菌感染和菌血症的蒃生率亦表蒃出下降蒃蒃。 在ICU中～蒃存在免疫功能抑制的患者;有高危因素的粒蒃胞缺乏患者～接受免疫抑制治蒃的高危蒃瘤患者～具有高危因素的肝移植与胰腺移植患者～高危的HIV感染患者,需蒃行蒃防治蒃～蒃防治蒃蒃持蒃到完全的免疫抑制治蒃蒃束～或持蒃到免疫抑制已出蒃蒃解。 推荐意蒃3,蒃免疫功能抑制的重症患者蒃蒃行抗菌蒃物的蒃真防治蒃 (推荐蒃蒃蒃A蒃) ICU有内气部分患者～如机械通蒃蒃超蒃48h～蒃期在ICU内停留蒃蒃超蒃72h～吻合口漏～感染性休克患者等～均蒃IFI的高危人群。有究蒃示～研靶真向蒃防治蒃能降低菌感染的蒃生率。但近期的Meta蒃示～蒃防性用蒃蒃降低了菌感染的蒃生率～但真未能改善蒃后～且同蒃存在耐蒃、花蒃增加的蒃蒃。由于蒃施蒃防用蒃存在有不可避免的副作用～蒃度使用又出会蒃耐蒃的危蒃～故尚来确需蒃行更大蒃模的蒃蒃明蒃防用蒃的蒃益人群。 推荐意蒃4,蒃ICU无免疫抑制的患者一内真般不蒃行抗菌蒃物的蒃防治蒃 (推荐蒃蒃蒃C蒃) 3,蒃防性抗菌蒃物蒃蒃的蒃蒃,真氟康蒃蒃蒃防大部分非光滑、非克柔的念珠菌感染能起到有益的作用～通常口服康氟蒃400mg/d。有部分究研建蒃首蒃量加倍;800mg,。当清肌蒃除率低于25ml/min蒃～蒃量要降至200mg/d。氟静脉康蒃使用蒃量成人蒃200,400 mg/d。 伊曲康蒃的抗菌蒃～可蒃展至曲非白念珠菌。蒃广霉与防治蒃通常用伊曲康蒃口服液400mg/d或静脉注射液200mg/d。蒃少减几胶口服液的胃蒃不良反蒃～可在初始天蒃合使用伊曲康蒃囊和口服液～或短期用静脉注射液后改口服制蒃。 蒃防性蒃用伏立康蒃可少减异霉肺移植患者和基因骨髓干蒃胞移植等患者曲感染的蒃生～但一蒃蒃防与研尚二蒃蒃防的究在蒃行中。 棘白菌素蒃～如卡与卡泊芬蒃米芬蒃～用于IFI的蒃防有效而安全～通常卡与卡泊芬蒃米芬蒃的蒃量蒃50mg/d。 两霉性素B脱氧胆酸蒃因其蒃注相蒃反蒃蒃与毒性～一般不用于蒃防治蒃。有究蒃示研,小蒃量的 ,1-1两霉性素B;0.2mg?kg重体?d,用于IFI蒃防是有益的。目前常以性素两霉B脂蒃体替代。究研两霉表明～危重肝移植患者蒃用性素B脂蒃可少曲感染的蒃生率～体减霉累蒃蒃量蒃1, ,1-11.5g～如同蒃接受蒃蒃替代治蒃～蒃量可增至5 mg?kg重体?d。近年西班牙的者蒃蒃了学5蒃 ,1-1两霉性素B脂蒃蒃体研用于肝移植患者的究～蒃果蒃示～用5 mg?kg重体?d两霉性素B脂蒃蒃体真防菌感染～有蒃好的蒃效。 氟胞蒃蒃的抗菌蒃相蒃窄～有明蒃的毒副作用～蒃蒃使用易出蒃耐蒃,故不推荐其作蒃蒃防蒃物使用。 六、重症患者IFI的治蒃 ;一,抗菌治蒃原蒃真 由于菌感染的蒃蒃性～真目前多提倡分蒃治蒃～包括蒃防性治蒃、蒃蒃性治蒃、蒃先治蒃及目蒃性治蒃。 1,蒃蒃性治蒃,蒃蒃的是蒃蒃IFI的患者～在未蒃得病原蒃学果之前～可考蒃蒃行蒃蒃性治蒃。蒃物的蒃蒃蒃蒃合考蒃可能的感染部位、病原菌、患者蒃真广防用蒃的蒃蒃及蒃物的蒃、有效、安全性和效价比等因素。 蒃于蒃蒃性治蒃的究研减目前主要集中在持蒃蒃蒃的中性粒蒃胞少症患者。蒃于蒃蒃患者蒃用蒃蒃、棘白菌素蒃及多蒃蒃蒃物～蒃床症状改善明蒃。 推荐意蒃5,蒃于蒃蒃IFI重症患者～蒃蒃行蒃蒃性抗菌治蒃;真荐推蒃蒃蒃E蒃, 2,蒃先治蒃,蒃蒃的是蒃床蒃断IFI的患者。蒃有高危因素的患者蒃展蒃蒃蒃蒃～包括每周2次胸部蒃片、CT蒃描、菌真真阳即真即培蒃及菌抗原蒃蒃等。如蒃蒃性蒃果～立蒃始抗菌治蒃～蒃先治蒃。其重要意蒃在于可能尽当真真医降低不恰的蒃蒃性治蒃所致的抗菌蒃物的不必要使用～降低菌耐蒃及蒃花蒃增加的可能性。蒃有的蒃于蒃先治蒃蒃蒃性治蒃比蒃的究蒃示～患者存与研异活率无差～蒃蒃性治蒃的花蒃蒃与真用的抗菌蒃物相蒃更多。 蒃先治蒃有蒃于蒃床生的医断清学断警蒃性及蒃蒃室蒃技蒃的蒃步。新的血蒃蒃方法～包括半乳甘露聚糖蒃蒃、β-D-葡聚糖蒃蒃以及蒃于菌真异特DNA的PCR技蒃～蒃床与征象、微生物培蒃～尤其是CT蒃描一起～蒃蒃始蒃先治蒃、蒃蒃疾病病程、蒃价治蒃反蒃提供了更多有参考价蒃的蒃料。蒃先治蒃的蒃物蒃蒃蒃依据蒃蒃到的菌蒃蒃而定。治蒃蒃真足量、足蒃程～以免蒃蒃。 推荐意蒃6,蒃ICU内蒃床蒃断IFI患者建蒃行蒃先治蒃～同蒃蒃一步蒃病原蒃据;找学荐推蒃蒃蒃E蒃, 推荐意蒃7,蒃ICU内IFI高危患者～蒃蒃展蒃蒃蒃蒃～避免不恰当尽的蒃蒃性治蒃～可能蒃施蒃先治蒃;推荐蒃蒃蒃C蒃, 3,目蒃治蒃,蒃蒃的是蒃确IFI的患者。蒃蒃菌蒃蒃蒃行真异真特性抗菌治蒃。以蒃得致病菌的蒃敏蒃果蒃依据～采用有蒃蒃性的治蒃～也可适当来参依据蒃蒃治蒃的蒃效蒃合蒃敏蒃果蒃整用蒃。蒃物蒃蒃要考蒃物抗菌蒃、蒃理特点学真、菌蒃蒃、蒃床病情和患者耐受性等因素后蒃定。 蒃微生物蒃蒃的侵蒃性念珠菌感染～主要蒃蒃合蒃学敏蒃果蒃行用蒃。白念珠菌、蒃蒃念珠菌、近平滑念珠菌蒃氟氟康蒃敏感～同蒃也可蒃蒃其他蒃蒃、 棘白菌素蒃等蒃物～光滑念珠菌、克柔念珠菌因蒃康蒃有不同程度的耐蒃～治蒃蒃不蒃首蒃氟卡两霉康蒃～而蒃蒃蒃伊曲康蒃、伏立康蒃、泊芬蒃、性素B及其含脂蒃等。体 大部分侵蒃性曲感染的患者多蒃蒃蒃或蒃床蒃～少患者能蒃。霉断数确断由于其蒃困蒃～易出蒃治蒃不足或治蒃蒃度。 ;二,器官功能障碍与真抗菌治蒃 ICU患者是IFI的高危人群～且往往均存在多器官功能障碍或衰竭～而蒃床常用的抗菌真蒃几真确与真乎均有肝蒃毒性及其他毒副作用。在抗菌治蒃蒃程中～如何正蒃蒃合理使用抗蒃菌蒃物～尽减可能避免或少器官蒃害～是ICU生医必蒃面蒃的蒃蒃。 1,常用抗菌蒃物蒃器官功能的真响影,性素两霉B脱氧胆酸蒃抗菌蒃～蒃床蒃广广用泛～但毒副作用多。使用蒃程中常出蒃高蒃、寒蒃、蒃吐、静脉炎、低蒃血症及肝蒃功能蒃害等毒性反蒃。 与两霉性素B脱氧胆两霉酸蒃相比～性素B含脂制蒃注射相蒃蒃症少～蒃并毒性明蒃降低～肝毒性无明蒃差异两霉。其中性素B脂蒃的蒃体并两霉毒性及注射相蒃蒃症最少～但性素B胆固醇蒃合的蒃体并两霉毒性蒃生率蒃高～寒蒃、蒃蒃等注射相蒃蒃症的蒃生率也高于性素B脂蒃。体 几真乎所有的蒃蒃抗菌蒃均有肝蒃毒性～但目前缺乏尚ICU患者使用蒃蒃蒃物蒃生肝功能蒃害的大蒃模蒃床蒃蒃。氟响真康蒃蒃肝蒃功能的影相蒃蒃小～是目前蒃床最常用的抗菌蒃。伊曲康蒃蒃肝蒃等器官的功能有一定影响～但蒃毒性明蒃低于性素两霉B脱氧胆酸蒃～其引起肝蒃害多表蒃蒃胆淤汁蒃。蒃充血性心力衰竭或在伊曲康蒃治蒃中出蒃心力衰竭或症加重的患者～蒃重新蒃状价使用蒃蒃的必要性。与两霉性素B脱氧胆酸蒃相比～伏立康蒃的肝蒃毒性明蒃少～其减另肝毒性具有蒃量依蒃性。外～蒃用伏立康蒃可出蒃短蒃蒃蒃障碍与幻蒃～一般停蒃后多可恢蒃。 以卡卡泊芬蒃、米芬蒃蒃代表的棘白菌素蒃蒃物主要在肝蒃代蒃～可引起肝功能常～异但蒃毒性明蒃低于性素两霉B脱氧胆卡酸蒃。米芬蒃的不良反蒃与卡泊芬蒃蒃似～可蒃致血蒃素增高胆～但几乎不影响蒃功能。 推荐意蒃8,抗菌蒃物治蒃蒃真状响充分考蒃基蒃肝蒃功能蒃以及蒃物蒃肝蒃功能的影 (推荐蒃蒃蒃E蒃) 2,肝蒃功能蒃害蒃抗菌蒃物的蒃蒃,真 ;1,肝功能不全蒃蒃物的蒃蒃蒃与氨量蒃整,肝功能不全患者蒃用蒃蒃蒃物蒃密切蒃蒃肝功能。蒃蒃蒃度升高但无明蒃肝功能不全的蒃床表蒃蒃～可在密切蒃蒃肝功能的基蒃上蒃蒃用蒃～蒃蒃升高正常氨达5倍以上并并出蒃肝功能不全的蒃床表蒃蒃～蒃考蒃停蒃～密切蒃蒃肝功能。 伊曲康蒃用于肝硬化患者蒃～其除清会半衰期延蒃～蒃考蒃蒃整蒃量。蒃蒃氨蒃明蒃升高、有活蒃性肝病或出蒃蒃蒃物性肝蒃蒃的患者蒃慎用伊曲康蒃。 在蒃度或中度肝功能不全患者中～可在密切蒃蒃肝功能的情下况使用伏立康蒃～第一天蒃荷量不蒃～之后蒃持蒃量半减尚研。目前无伏立康蒃蒃用于蒃重肝功能障碍患者的究。 卡泊芬蒃在蒃度肝功能障碍(Child-Pugh蒃分5,6)蒃不需量减～中度肝功能障碍(Child-Pugh蒃分7,9)蒃需量减至35mg/d。目前无重尚度肝功能障碍(Child-Pugh蒃分>9分)患者的用蒃究～研减若存在重度肝功能障碍蒃考蒃蒃一步量或停蒃。 ;2,蒃功能障碍或衰竭蒃蒃物的蒃蒃蒃与量蒃整,氟康蒃80%由原型蒃蒃蒃排出～肌蒃除率清>50ml/min蒃无需蒃整用蒃蒃量～肌蒃除率清<50ml/min蒃蒃量半减。 伊曲康蒃其蒃形蒃蒃丙基-β-蒃糊精从清蒃蒃代蒃～故肌蒃除率<30ml/min蒃～不推荐静脉蒃蒃。口服液的生物利用度蒃胶达囊有所提高～53%以上～若患者蒃道吸收功能可蒃可尚考蒃改蒃口服用蒃～空腹服用可提高生物利用度。 伏立康蒃其蒃形蒃磺丁-β-蒃糊精蒃蒃蒃从清代蒃～故肌蒃除率<50ml/min蒃～不推荐静脉蒃蒃。口服制蒃生物利用度达95%以上～若患者蒃道吸收功能可～可尚考蒃改蒃口服用蒃。 卡泊芬蒃主要在肝蒃代蒃～蒃功能障碍患者无需蒃整蒃量。 3,器官功能障碍蒃性素两霉B的使用,延蒃性素两霉B的蒃注蒃蒃可少其蒃减与毒性相蒃的寒蒃、高蒃等毒性反蒃。究蒃蒃～研24h持蒃静脉两霉注射或延蒃性素B脱氧胆酸蒃的蒃注蒃蒃～可增加患者蒃其耐受性～少低蒃、低蒃血症的蒃生～减并另降低蒃毒性。外～两霉性素B脱氧胆酸蒃价格便宜～故24h持蒃静脉注射两霉性素B脱氧胆酸蒃仍可作蒃治蒃IFI的手段。 推荐意蒃9,延蒃性素两霉B脱氧胆酸蒃的蒃注蒃蒃可增加患者蒃蒃物的耐受性～少蒃减毒性 (推荐蒃蒃蒃C蒃) 蒃用两霉性素B蒃～蒃尽并量避免合蒃用有肝蒃毒性的蒃物。非蒃抗甾体氨苷炎蒃、基糖蒃抗生素、造影蒃、蒃蒃素A、他克莫司等具有明蒃的蒃毒性～与其合用蒃～可增加蒃蒃害的危蒃性。外～蒃另尽量避免性素两霉B与响可能影肝功能的蒃物同蒃使用～以免增加肝蒃胞膜的通透性～出蒃肝蒃蒃害。 在使用两霉性素B脱氧胆酸蒃的蒃程中～如出蒃蒃蒃基蒃疾病蒃化或血肌蒃蒃行性升高、使用糖皮蒃激素及抗蒃等蒃物仍胺出蒃蒃以耐受的注射相蒃副作用、使用蒃物蒃量,500mg仍无效蒃～蒃考蒃蒃蒃。 使用两霉性素B出蒃的蒃功能蒃害～在停蒃后数数日至月后可逐蒃恢蒃～永久性的蒃衰竭少蒃。两霉性素B的蒃毒性蒃与量呈正相蒃。蒃功能蒃害大多蒃生于使用大蒃量两霉性素B后(蒃蒃量,4g)。多蒃究蒃示～蒃研两霉用不同蒃量的性素B脂蒃治蒃体IFI～蒃效并异两霉无蒃著差～但性素B脂蒃蒃体量 -1-1越大～蒃功能蒃害及低蒃血症的蒃生率越高。一般蒃蒃～性素两霉B脂蒃体3,5mg?kg重体?d蒃蒃适宜～不宜蒃一步增加用蒃蒃量。 4,血液透析与真与学响血液蒃蒃蒃抗菌蒃物蒃量的蒃整,血液透析血液蒃蒃蒃蒃代蒃力的影因素蒃蒃多蒃～主要影响数运数因素有蒃物分子量、分布容蒃、血蒃蛋白蒃合率、蒃蒃系、室蒃蒃速率常、蒃物代蒃途径(蒃蒃蒃除的比例清)、超蒃率等。蒃物分子量越小、血蒃蛋白蒃合率越低～蒃血液透析与血液蒃蒃蒃清数与清除越多～若蒃物蒃蒃系低～蒃血液透析血液蒃蒃蒃除蒃少。 两霉性素B含脂制蒃蛋白蒃合率高～血液蒃蒃蒃无需蒃整蒃量。氟康蒃蛋白蒃合率低～血液透析与清血液蒃蒃蒃能蒃除～故于每次透析后常蒃蒃量蒃蒃1次。伊曲康蒃的蛋白蒃合率蒃99%～血液透析 不影响静脉或口服的半衰期与清除率～但β-蒃糊精可蒃血液透析清除～故血液透析蒃伊曲康蒃蒃蒃蒃量不蒃～只需在血液透析前蒃蒃～以便清除β-蒃糊精。伏立康蒃主要在肝蒃代蒃～血液透析与血液蒃蒃蒃无需蒃整蒃量。卡泊芬蒃主要在肝蒃代蒃～血液蒃蒃血液与透析蒃亦无需蒃整蒃量。 推荐意蒃10,接受血液蒃化的重症患者蒃行抗菌真治蒃蒃～蒃根据蒃物的除率蒃清来整蒃物蒃量(推荐蒃蒃蒃D蒃) ;三,免疫蒃蒃治蒃 蒃IFI的治蒃蒃包括免疫蒃蒃治蒃～主要包括胸腺蒃α1;thymosinα1,、IL、粒蒃胞集落刺激因子;G-CSF,、粒-巨噬蒃胞集落刺激因子;GM-CSF,和巨噬蒃胞集落刺激因子;M-CSF,、粒蒃胞蒃注等。免疫蒃蒃治蒃的目的是增加中性粒蒃胞、蒃蒃噬数噬胞的量～激活中性粒蒃胞、蒃蒃胞和蒃突状真减研蒃胞的蒃菌活性～增强蒃胞免疫～蒃短中性粒蒃胞少症的持蒃蒃蒃等。有究表明～免疫治蒃可改善中性粒蒃胞减少症IFI患者的蒃后～但缺乏大蒃尚随研模机蒃照究。 ;四,外科治蒃 有些IFI需要行外科手蒃治蒃～如曲蒃～外科霉确摘除是明的治蒃方法～蒃鼻蒃感染的治蒃蒃蒃合蒃物外科与清与方法～外科蒃蒃内引流在治蒃中十分重要～蒃心蒃膜炎患者蒃行心蒃瓣膜置蒃手蒃～且蒃后要蒃施蒃物治蒃。当然～蒃IFI患者需要蒃施外科治蒃的情况很蒃多～如枢骨髓炎、心包炎、中蒃神蒃系蒃感染引起的蒃蒃蒃等。内 附蒃,IFI的治蒃蒃物蒃述 与真国当并其他抗感染蒃物不同～目前抗菌蒃物在中市蒃可蒃蒃范蒃相有限～且受限于蒃蒃、蒃蒃蒃定条医真体个况并参件和生蒃菌感染的蒃蒃。具蒃用蒃要蒃合患者人情～照蒃品蒃明蒃。 一、多蒃蒃 1,性素两霉B,;1,适蒃蒃,可用于曲、念珠菌、蒃霉球菌、蒃蒃胞蒃菌等引起的IFI。;2,蒃代蒃力学几静脉屏,乎不被蒃道吸收～蒃蒃蒃蒃理想。血蒃蒃合率高～可通蒃胎蒃障、血蒃半衰期蒃24h。蒃蒃除清很慢。;3,用法与静脉用量,蒃蒃～每天0.5,1.0mg/kg重。;体4,注意事蒃,蒃蒃的两性素霉B制蒃具有蒃重的蒃毒性～需蒃患者蒃行蒃密的蒃功能及血蒃水平蒃蒃。蒃功能蒃当减著下降蒃蒃予量～蒃并与避免其他蒃毒性蒃物合用。 2,性素两霉B含脂制蒃,目前有3蒃制蒃性素——两霉B脂蒃蒃合体(ABLC)、性素两霉B胶蒃分散体(ABCD)、性素两霉B脂蒃体(L-AmB),因其分布更集中于蒃核-蒃蒃噬胞系蒃如肝、脾和肺蒃蒃,少了在蒃蒃蒃的蒃减度,故蒃毒性蒃性素两霉B去氧胆体酸蒃低。由于采用脂蒃技蒃制蒃,故价格蒃蒃。昂;1,适蒃蒃: 可用于曲、念珠菌、蒃霉球菌、蒃蒃胞蒃菌等引起的IFI～无法耐受蒃蒃性素两霉B制蒃的患者～蒃功能蒃重蒃害,不能使用蒃蒃性素两霉B 制蒃的患者。;2,蒃代蒃力学:非蒃性蒃力学,易在肝蒃 及脾蒃中蒃集,蒃蒃中蒃蒃少蓄蒃。;3,用法与用量: 推荐蒃量ABLC蒃5 mg/kg重体, ABCD蒃3,4 mg/kg重体, L-AmB蒃3,5 mg/kg重。体起始蒃量蒃每天1mg/kg重体,蒃蒃治蒃的推荐蒃量蒃每天3mg/kg重体,蒃治蒃蒃确每天3 mg/kg重或体5mg/kg重体,蒃静脉注蒃蒃不蒃少于1h。;4,注意事蒃:蒃毒性蒃著降低,蒃液反蒃亦大大少减,但仍需蒃蒃蒃功能。 二、蒃蒃 1,氟康蒃,;1,适蒃蒃,深部念珠菌病、急性蒃球菌性蒃膜炎、侵蒃性念珠菌病的蒃防与治蒃。;2,蒃代蒃力学响清,口服迅速吸收～蒃食蒃蒃物吸收无影。蛋白蒃合率低～蒃蒃除～血蒃半衰期蒃20,30h～血中蒃物可蒃透析清除。;3,用法与用量,侵蒃性念珠菌病400,800mg/d～念珠菌病的蒃防,50,200mg/d,蒃程不宜超蒃2,3周。;4,注意事蒃,蒃期治蒃者注意肝功能。 2,伊曲康蒃,;1,适蒃蒃,曲、念珠菌、蒃霉属属球菌和蒃蒃胞蒃菌等引起的IFI。;2,蒃代蒃力学,蛋白蒃合率蒃99%～血蒃半衰期蒃20,30h。蒃肝P蒃系广胆与泛代蒃～代蒃蒃物蒃汁尿液排450 泄。;3,用法与用量,第1,2天200mg,静脉注射～每天2次～第3,14天200mg,静脉注射～每天1次;蒃注蒃蒃不得少于1h～之后序蒃使用口服液～200mg每天2次。;4,注意事蒃,蒃期治蒃蒃蒃注意蒃蒃肝功能～不得其他与静脉与肝毒性蒃物合用～蒃蒃不得其他蒃物采用同一通路。 3,伏立康蒃,;1,适蒃蒃,免疫抑制患者的蒃重菌感染、真霉氟急性侵蒃性曲病、由康蒃耐蒃的念珠菌引起的侵蒃性感染、蒃刀霉菌引起的感染等。;2,蒃代蒃力学,高危患者中呈非蒃性蒃代蒃力学～蛋白蒃合率蒃58%～蒃蒃分布容蒃蒃4.6L/kg重～除体清半衰期蒃6,9h。;3,用法与用量,蒃荷蒃量,蒃静脉予6mg/kg重体,每12h 1次～蒃用2次。蒃注速度不得超蒃每小蒃3mg/kg重～体在1,2h蒃内完。蒃持蒃量:蒃静脉予4 mg/kg重体,每12 h 1次。;4,注意事蒃,中,重度蒃功能不全患者重蒃蒃蒃。慎静脉 三、棘白菌素蒃 1,卡泊芬蒃,;1,适蒃蒃,蒃蒃性中性粒蒃胞减真并少患者疑似菌感染的蒃蒃性治蒃～用于治蒃侵蒃性念珠菌病、念珠菌血症及其他蒃法蒃控制或不能耐受的侵蒃性曲菌病。;霉2,蒃代蒃力学,血蒃蒃度与蒃量呈等比例增蒃～蛋白蒃合率,96%～除清半衰期蒃40,50h。;3,用法与用量,首日蒃予一次70mg蒃荷蒃量,随后50mg/d蒃持～蒃注蒃蒃不得少于1h～蒃程依患者病情而定。;4,注意事蒃,蒃肝功能受蒃的患者重慎用蒃。 2,米卡属霉属真芬蒃,是一蒃新型水溶性棘白菌素蒃脂蒃～蒃念珠菌、曲菌引起的深部菌感染有蒃抗菌作广用～蒃耐蒃蒃蒃物的白念珠菌、光滑念珠菌、克柔念珠菌及其他念珠菌均有良好的抗菌活性～但不能抑制新型蒃球菌、毛蒃子菌、蒃蒃或蒃合菌。属属属与霉目前主要用于念珠菌曲菌所致的属真体内广与胆深部菌感染。本品分布泛～血蒃蒃蒃蒃度蒃高～主要在肝蒃代蒃～蒃汁排泄～ 与异其他蒃物相互作用少。主要不良反蒃是肝功能常,但蒃生率不高。其并用于治蒃食管念珠菌病 的推荐蒃量蒃150mg/d～蒃防造血干蒃胞移植患者念珠菌感染的推荐蒃量蒃50mg/d。 四、氟胞蒃蒃 ;1,适蒃蒃,少蒃一很两霉用蒃～一般蒃合性素B蒃用于全身念珠菌病、蒃球菌病。;2,蒃代蒃 力学几达,口服迅速～乎完全吸收～蒃口和非胃蒃道蒃蒃均可到相同的血蒃蒃度～蛋白蒃合率低～ 蒃蒃分布泛广～蒃蒃蒃以原形消除～血蒃半衰期蒃2.5,5.0h。;3,用法与用量,若蒃功能正常～初 始蒃量50,150mg/kg重分体4次蒃蒃～6h 1次～若蒃功能不全～初始蒃量25mg/kg重～但体随 后的用量与清达蒃期需蒃整～以使血峰蒃蒃度到70,80mg/L。;4,注意事蒃,每周蒃蒃血肌蒃水平 2次～蒃整合适蒃量～蒃律蒃蒃血蒃胞蒃数与当与两霉肝功能～性素B蒃用蒃～性素两霉B会氟使胞 蒃蒃的除率清降低。 中蒃重症分侵蒃性菌感染指南工作蒃 医学会医学会真 蒃蒃,王蒃霞;中科院 中蒃和科大 国医学学国医学医北京蒃和院感染科, 成蒃;按姓氏排列笔划,,于蒃江;哈蒃蒃科大附第二院医学属医ICU,～方强;浙江大附学 属医第一院ICU,～大蒃;中科院 中蒃和科大 刘国医学学国医学医医北京蒃和院加强蒃科,～ 安友仲;北京大人学医民院ICU,～李若瑜;北京大第一院 学医皮蒃科,～邱海波;蒃南大 学属医附中大院ICU,～徐英春;中科院 中蒃和科大 国医学学国医学医北京蒃和院蒃蒃科,～ 黎毅敏;广医学属医广研州院第一附院 州呼吸疾病究所ICU, 表1 CVVH、CVVHD或CVVHDF及IHD蒃抗菌蒃物的蒃真量蒃整 蒃物名称CVVHCVVHD或CVVHDFIHD氟康蒃200,400mg～400,800 mg～于每次血液透析后 每24h一次每24h一次蒃蒃一次伏立康蒃4mg/kg重体～口服～4mg/kg重体～口服～ 每12h一次每12h一次 伊曲康蒃,,血液透析前蒃蒃卡泊芬蒃无需蒃整蒃量 两霉性素B 两霉性素B脱氧胆酸蒃0.4,1.0mg/kg重体～0.4,1.0mg/kg重体～ 每12h一次每12h一次 3,5mg/kg重体～3,5mg/kg重体～两霉体性素脂蒃蒃合每24h一次每24h一次 3,5mg/kg重体～3,5mg/kg重体～ 每24h一次两霉性素B脂蒃体每24h一次 注,CVVH,蒃蒃静脉静脉,血液蒃蒃～CVVHD,蒃蒃静脉静脉,血液透析～CVVHDF,蒃蒃静脉 ,静脉血液透析蒃蒃～IHD ,蒃歇性血液透析～CVVH、CVVHD或CVVHDF蒃～置蒃液、透析 液均蒃1L/h 参献考文, [1] Martin GS, Mannino DM, Eaton S, Moss M. 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