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影音先锋下载 【大家共鸣】相连性肾替代治疗抗菌药物剂量改变大家共鸣(2024年版)
发布日期:2024-09-19 18:05 点击次数:65
相连性肾替代治疗抗菌药物剂量改变共鸣大家组 中国药学会病院药学专科委员会 中国医药说明协会感染疾病专科委员和会信作家:卢晓阳,浙江大学医学院附庸第一病院临床药学部,杭州 310003,Email:luxiaoyang@zju.edu.cn;蔡急流,浙江大学医学院附庸第一病院重症医学科,杭州 310003,Email:1193001@zju.edu.cnDOI:10.3760/cma.j.cn441217-20230906-00906摘 要 相连性肾替代治疗(continuous renal replacement therapy,CRRT)是临床危重症患者迫切的治疗技能。危重症患者往往需要同期接受抗菌药物和CRRT治疗。在CRRT时间,抗菌药物的药代能源学和药效学均可能受到影响,现时尚缺少CRRT时间抗菌药物治疗剂量的保举和漠视。国内临床医学、药学、重症医学以及感染病学大家设立CRRT抗菌药物剂量改变共鸣大家组,围绕CRRT身分、药物特点、患者身分及CRRT时间各类抗菌药物使用基本原则进行字据检索,并充分有筹商,制定了该共鸣,以期为CRRT时间合理使用抗菌药物提供指引漠视。要道词 相连性肾替代疗法;危重症照管;抗微生物药物处理;剂量改变;大家共鸣相连性肾替代治疗(continuous renal replacement therapy,CRRT)是指一组体外血液净化的治疗时期,是整个相连、逐渐吊销水分和溶质治疗神气的总称,已成为多样危重症救治中迫切的援助治疗程序之一[1]。传统CRRT应捏续治疗24 h以上,但临床上可根据患者的治疗需求机动改变治疗时辰[2]。严重感染和感染性休克是急性肾挫伤(acute kidney injury,AKI)常见的发病原因之一[3],此类患者常需要接受CRRT。重症感染导致了重症监护病房内>50%的AKI[4],因此接受CRRT的危重症患者往往同期使用多种抗菌药物。对于接受CRRT的患者,多种身分如CRRT身分、药物身分、患者身分等可能会影响抗菌药物的药代能源学(pharmacokinetics,PK)/药效学(pharmacodynamics,PD)[5]。抗菌药物剂量使用不妥可能导致药物不良响应增多、病原菌耐药和临床治疗失败。本共鸣旨在为临床接受CRRT的危重症患者抗菌药物使用提供漠视,以保险抗菌药物使用的灵验性和安全性。一、共鸣变成要领共鸣大家小组由重症医学、感染病学、肾内科临床医学和药学大家构成,共鸣援笔大家组讲求共鸣草拟,在前期共鸣大家小组商议会及函询的基础上变成拟保举主意,并基于保举分级的评估、制订与评价(grading of recommendations assessment,development and evaluation,GRADE)网格,行使更动的德尔菲法,通过投票表决达成共鸣。达成共鸣的投票端正如下(表1):若除了“0”除外的任何一格票数杰出50%,则视为达成共鸣,可径直坚信保举主意标的及强度;若“0”某一侧2格总票数杰出70%,亦视为达成共鸣,可坚信保举主意标的,保举强度则径直定为“弱”;其余情况视为未达成共鸣,插附近一轮投票。通过共鸣大家小组投票表决,本共鸣就CRRT中抗菌药物剂量改变的33条保举主意达成共鸣,其中21条变成强保举,12条变成弱保举。 图片影音先锋下载影音先锋下载影音先锋下载 二、CRRT身分对CRRT中抗菌药物剂量的影响保举主意1. CRRT不同形状及治疗剂量使药物吊销存在各异,抗菌药物剂量改变时应玄虚研讨患者接受CRRT的形状及治疗剂量。(保举级别:强保举)CRRT包括多种形状,不同形状的吊销机制、滤器种类、置换液和/或透析液流速、补充神气等性能和参数各异可影响药物和溶质的吊销。(一) CRRT形状现时CRRT主要治疗形状包括:捏续静脉-静脉血液滤过(continuous veno-venous hemofiltration,CVVH)、捏续静脉-静脉血液透析(continuous veno-venous hemodialysis,CVVHD)以及捏续静脉-静脉血液透析滤过(continuous veno-venous hemodiafiltration,CVVHDF)。上述形状波及的3种主要吊销神气包括:血液滤过、血液透析以及血液透析滤过,不同形状的吊销神气其液体置换机制不同。CVVH吊销机制主要为对流作用,指溶质随同溶剂通过半透膜的移动,其不受溶质分子量和浓度梯度差的影响,跨膜能源是膜两侧的静水压差,治疗时需使用置换液。CVVH形状在静水压力驱动下,中、小分子药物易进行跨膜转运。CVVHD吊销机制主要为弥漫作用,指溶质依靠膜两侧浓度差跨膜转运,治疗时需使用透析液。CVVHD形状下,小分子药物易从高浓度侧通过弥漫作用向低浓度侧转换。与弥漫形状比拟,对流形状可去除分子量较大的药物[6]。CVVHDF同期合股了对流和弥漫机制,溶质通过浓度梯度及压力梯度吊销,治疗时需要同期使用置换液和透析液。针对不同CRRT形状,有研究觉得药物的吊销遵守为CVVHDF>CVVHD>CVVH[7]。(二) CRRT滤器CRRT滤器在通透性、膜材料和膜面积方面的不同,可导致药物吊销率存在各异。药物通过滤器的才略不错用筛分总共(sieving coefficient,SC)和足够总共(saturation coefficient,SA)来示意。SC和SA分裂示意超滤液(SC)和透析液(SA)中溶质浓度与血液溶质浓度的比值[8]。SC或SA=0代表整个药物弗成通过滤器,而SC或SA=1代表整个药物不错通过CRRT滤器。一项“CATCH”前瞻性研究发现,利福平、替考拉宁、环丙沙星、左氧氟沙星、利奈唑胺、哌拉西林-他唑巴坦、好意思罗培南、永劫霉素、复方磺胺甲噁唑(磺胺甲噁唑-甲氧苄啶)在CVVH时间均具有较高的SC[9],指示CVVH对上述抗菌药物吊销率有较大的影响。与间歇性血液透析滤器比拟,CRRT滤器用有较大的孔径,不错灵验去除较大的分子。不同的CRRT膜材料影响抗菌药物的吊销。常见的CRRT滤膜包括聚砜、聚甲基丙烯酸甲酯和聚丙烯腈膜。在这些滤膜中,聚丙烯腈膜具有由丙烯腈/甲代烯丙基磺酸酯共聚物制成的氢结构,不错吸附多量卵白质。与聚砜比拟,聚丙烯腈膜接收抗菌药物才略较强。此外,CRRT滤器的名义积在往常几年里从0.6~0.9 m2增多到1.2~1.5 m2[10]。最近的1项研究标明,与0.9 m2滤膜滤器比拟,接受具有1.5 m2 AN69ST滤器的CVVHDF的患者需要更高的哌拉西林-他唑巴坦剂量[11]。因此改变剂量时应试虑CRRT时间的滤器特点。关联词,由于对CRRT滤器接收抗菌药物的研究有限,现时还莫得准确的剂量改变漠视。(三) 置换液补充神气与CRRT治疗剂量置换液补充神气可分为前稀释与后稀释。前稀释指置换液在滤器前与血流混杂;后稀释指置换液在滤器后加入。在后稀释形状下,血浆径直插足滤器,药物吊销率与流速及SC连接。前稀释形状下,血浆在插足滤器前被稀释,因此药物浓度在滤过前被稀释,比拟后稀释形状CRRT对其吊销减少[12]。CRRT治疗剂量是透析液流速(Qd)和超滤液流速(Qf)的总数。改善世界肾脏病预后组织2012年临床推行指南漠视接受CRRT的患者接受20~25 ml·kg-1·h-1的治疗剂量[13]。关联词,CRRT治疗剂量在临床推行中仍然存在很大各异。研究标明,较高的治疗剂量会增多某些药物的吊销率,可能需要更高的抗菌药物剂量。CRRT中药物吊销率与药物SC密切连接,不错通过SC、SA和CRRT治疗剂量诡计如下:一般来说,CVVHD形状下的吊销率(CLCVVHD)=Qd×SA;CVVHDF形状下的吊销率(CLCVVHDF)=(Qf Qd)×SA;CVVH后稀释形状下的吊销率(CLCVVH(post))=Qf×SC,而CVVH前稀释形状下的吊销率(CLCVVH(pre))尚需研讨血液流速(Qb)和置换液流速(Qrep)的影响,CLCVVH(pre)=Qf×SC×Qb/(Qb Qrep)[14]。但由于危重症患者存在个体各异,简便地根据流量改变剂量可能不及以确保达到抗菌药物PK/PD靶值。三、药物特点对CRRT中抗菌药物剂量的影响保举主意2. CRRT时间抗菌药物剂量改变应试虑药物特点,如分子量、卵白合股率、表不雅散布容积(apparent volume of distribution,Vd)和药物吊销道路。(保举级别:强保举)CRRT中药物吊销受其本身特点的影响(表2)。分子量、卵白合股率、Vd和药物吊销道路被觉得是CRRT时间PK参数的迫切影响身分。与低通量血液透析比拟,CRRT不错吊销大分子药物,大部分游离抗菌药物可经CRRT吊销,而药物与卵白合股会变成难以被CRRT吊销的大分子复合物。关联词,研究标明,一些具有高卵白联协力的抗菌药物具有高SC或SA[20],这可能是由于接受CRRT的危重症患者的个体各异大,如血液pH值变化、低卵白血症等。图片 Vd较大的药物(≥2 L/kg)在血管外散布泛泛或组织亲和力较高,反之,Vd较小的药物则在血管内浓度较高。亲脂性药物往往具有较大的Vd,受到较少的肾脏吊销,不易经由CRRT吊销,因此Vd较大的药物时常不需要改变剂量。Vd较小的药物多数为亲水性药物,大多数亲水性药物以原形经肾脏吊销,因此Vd较小的药物更容易被CRRT吊销,往往需要改变药物剂量。另外,CRRT行为捏续治疗技能,可能导致组织中药物再行散布而插足血管,从而莳植药物吊销率。药物吊销率是指单元时辰内血浆中的药物被皆备吊销的总量,即吊销率=药物吊销速度/血药浓度。总吊销率是指药物在不同器官吊销率的总数。接受CRRT时,药物吊销尚存在体外吊销进程,即存在体外吊销率。当体外吊销率大于总吊销率的25%时,时常觉得体外吊销具有迫切的临床好奇景仰[21]。与经非肾道路吊销药物比拟,CRRT赫然增多了经肾脏吊销药物的吊销率。经非肾道路吊销药物或肾脏吊销小于25%~30%,CRRT对药物吊销的影响较小,但研讨到CRRT对体液的吊销作用,CRRT也可能在一定进程上增多经由其他器官吊销药物的吊销率。对于主要经肾脏吊销的药物,在CRRT时间需进行剂量改变。对于主要经非肾道路吊销的药物,原则上不需要改变剂量。四、患者身分对CRRT中抗菌药物剂量的影响保举主意3. 对于接受CRRT的重症感染患者,应试虑器官功能景色并合股病原菌最低抑菌浓度(minimum inhibitory concentration,MIC)改变抗菌药物剂量,研讨到重症患者PK/PD存在个体各异,血药浓度监测是最好的抗菌药物剂量改变技能。(保举级别:强保举)重症患者往往伴有液体负荷改变,水肿、腹水、胸腔积液、低卵白血症等都可引起Vd增多,因此可能需要更高的抗菌药物剂量。重症患者由于疾病可能使抗菌药物PK改变,影响药物浓度[22](表3)。接受CRRT的患者随液体吊销增多,Vd相应减少,此时需要相应减少药物剂量。重症患者脏器功能受损往往导致药物吊销减少,此时需要减少剂量。而CRRT可能会增多药物的吊销,需要对应补充药物剂量,在改变药物剂量的同期,还需要研讨患者的残余肾功能。图片 抗菌药物可分为时辰依赖性和浓度依赖性药物。时辰依赖性抗菌药物的抗菌效应和临床疗效主要与血药浓度高于MIC的时辰关联,当血药浓度高于病原菌MIC的4~5倍时,不绝增多剂量,其杀菌效应不再增多,规划此类药物疗效的PK/PD参数主要为游离药物浓度杰出MIC的时辰(fT>MIC);浓度依赖性抗菌药物的抗菌效应和临床疗效取决于药物自满量,规划此类药物疗效的PK/PD参数主要为血药峰浓度(Cmax)/MIC或24 h药时弧线底下积(area under the curve,AUC)/MIC比值(AUC0~24 h/MIC)。因此对于接受CRRT的重症感染患者尚需研讨病原微生物对药物的敏锐度。药物负荷剂量一般由Vd决定,如患者存在水肿、腹水或液体超负荷,可导致Vd增多[23],需要对应增多负荷剂量,而存在脱水常需要镌汰负荷剂量。药物负荷剂量不受CRRT及患者残余肾功能影响,而防守剂量时常需通过PK/PD靶值和稳态血药谷浓度(Cmin)来坚信。基于患者个体各异,漠视对于接受CRRT的患者进行抗菌药物血药浓度监测,根据血药浓度监测限定改变药物剂量。五、CRRT时间各类抗菌药物使用基本原则本部分针对24 h捏续CRRT的无尿患者,依据文献报说念合股大家主意保举不同抗菌药物剂量改变有筹算(表4)。基于现存字据不及以给出保举主意的药物,在本共鸣中未纳入。图片 (一)抗细菌药物1. β-内酰胺类抗菌药物:β-内酰胺类抗菌药物多数经肾脏吊销,可被CRRT吊销,CRRT时间需要对应改变剂量。(1) 头孢菌素类:保举主意4. CRRT不同形状下使用头孢菌素类药物可参考肾功能浅薄患者的剂量给药。(保举级别:弱保举)5. 在重症感染或病原菌MIC较高时,漠视给以头孢他啶负荷剂量2 g,防守剂量CVVHDF形状下3 g qd捏续输注或CVVH形状下2 g q8 h延迟输注4 h。(保举级别:弱保举)6. 在重症感染或病原菌MIC较高或接受较高CRRT治疗剂量时,漠视给以头孢吡肟2 g q8 h延迟输注4 h或捏续输注。(保举级别:弱保举)7. 头孢曲松在CRRT时间无需改变剂量。(保举级别:强保举)早期研究保举在CVVH形状下给以头孢吡肟1~2 g q12 h,在CVVHD或CVVHDF形状下给以头孢吡肟1 g q8 h或2 g q12 h[24-25]。近期研究发当今CVVH和CVVHDF时间头孢吡肟PK参数存在各异,蒙特卡罗模拟分析自满在CVVH或CVVHDF形状下,头孢吡肟2 g q8 h适用于较高的CRRT治疗剂量(>1.5 L/h[26]或20 ml·kg-1·h-1[27]),而1 g q8 h适用于较低的CRRT治疗剂量(≤1 L/h)[26]。针对亚洲危重症患者分析的研究自满,头孢吡肟2 g q8 h在CVVH治疗剂量为20~40 ml·kg-1·h-1时均可达到灵验PK/PD靶值(≥60% fT>4×MIC)[28]。头孢吡肟最好剂量应根据CRRT形状、CRRT治疗剂量以及MIC进行改变[29]。对于MIC较高的病原菌,可研讨延迟输注时辰以莳植头孢菌素类抗菌药物在CRRT时间的疗效。一项前瞻性研究发现,在接受CVVHDF形状治疗(透析液流速1 L/h、置换液流速1.5 L/h)的7例危重症患者中,给以头孢他啶2 g负荷剂量后,通过逐日捏续输注3 g头孢他啶不错保证血药浓度/MIC>4[30]。在CVVH形状下,当CRRT治疗剂量为20~30 ml·kg-1·h-1时,给以头孢他啶负荷剂量2 g输注0.5 h,防守剂量2 g q8 h并延迟输注4 h可在48 h内完好意思PK/PD靶值(≥60%fT>4×MIC)[27]。一项前瞻性研究自满头孢吡肟延迟输注时辰可莳植CVVH和CVVHD时间的PK/PD靶值达标率,头孢吡肟2 g q8 h延迟输注4 h,可使MIC=8 mg/L的病原菌感染患者达到100%fT>MIC,10例患者中有1例达到100%fT>4×MIC[31]。对于MIC≤8 mg/L的病原菌感染,头孢吡肟2 g q8 h间歇输注可达到PK/PD靶值(100%fT>MIC),而对于MIC=16 mg/L的病原菌感染需延迟输注4 h或捏续输注[32]。头孢曲松经胆汁、肾脏双通说念吊销,接受CVVH治疗患者的头孢曲松吊销率与肾功能浅薄受试者的吊销率接近[24]。CVVH党羽孢曲松的吊销率约占总吊销率的70%,头孢曲松旧例剂量1 g qd可灵验用于MIC≤2 mg/L的病原菌感染[33]。(2) β-内酰胺酶遏止剂复方制剂:保举主意8. CRRT不同形状下使用β-内酰胺酶遏止剂复方制剂可参考肾功能浅薄患者的剂量给药。(保举级别:弱保举)9. CVVHDF治疗剂量为3.0~3.5 L/h时,漠视给以哌拉西林-他唑巴坦4.5 g q8 h;CVVH治疗剂量为20~40 ml·kg-1·h-1时,漠视给以哌拉西林-他唑巴坦3.375 g q6 h;对于MIC=32 mg/L的病原菌感染,漠视给以哌拉西林-他唑巴坦4.5 g q6 h,必要时捏续输注或延迟输注4 h。(保举级别:强保举)10. 在重症感染或病原菌MIC较高时,CVVH时间漠视头孢哌酮-舒巴坦根据舒巴坦剂量诡计,给以舒巴坦≥1 g q8 h,必要时捏续输注或延迟输注。(保举级别:弱保举)哌拉西林-他唑巴坦可被不同形状CRRT吊销。与CVVH形状比拟,CVVHDF形状下哌拉西林的吊销率较高[7.5(5.9,11.2)L/h比4.7(4.5,9.6)L/h,P=0.21],但两者各异无统计学好奇景仰[34]。CVVHDF形状与CVVHD形状下哌拉西林-他唑巴坦PK/PD参数无显耀各异[35]。一项前瞻性研究自满,CVVHDF治疗剂量为3.0~3.5 L/h时,哌拉西林-他唑巴坦4.5 g q8 h可使哌拉西林血药浓度>32 mg/L[36]。针对亚洲东说念主的蒙特卡罗模拟分析研究自满,CVVH治疗剂量为20~40 ml·kg-1·h-1 时,哌拉西林-他唑巴坦3.375 g q6 h可在48 h内达到PK/PD靶值(≥60%fT>MIC)[28]。CVVH形状下,对于MIC=32 mg/L的病原菌感染,给以哌拉西林-他唑巴坦4.5 g q6 h可使PK/PD靶值(100%fT>MIC)达标概率≥90%[37]。与间歇推注比拟,CRRT时间哌拉西林-他唑巴坦捏续输注或延迟输注4 h不错显耀莳植PK/PD靶值达标率,尤其适用于MIC较高的病原菌感染或感染性休克患者[34,38-41]。头孢哌酮-舒巴坦中头孢哌酮主要经胆汁吊销,舒巴坦主要经肾脏吊销。基于氨苄西林-舒巴坦的研究,早期研究漠视CVVH形状给以舒巴坦1 g q12 h,CVVHD或CVVHDF形状下给以舒巴坦1 g q8 h[24]。在接受CVVH形状治疗的危重症患者中,舒巴坦的PK发生显耀改变,对于接受1 g q8 h舒巴坦的患者唯独约37.5%的患者Cmin>8 mg/L,因此对于不太敏锐的病原菌,在CVVH时间可能需要更高的剂量[42]。到现时为止,舒巴坦在CVVHDF和CVVHD下的PK/PD数据尚未更新。因此,漠视给与血药浓度监测来个体化改变剂量。头孢他啶-阿维巴坦是一种新式β-内酰胺-β-内酰胺酶遏止剂组合,用于治疗多重耐药革兰阴性菌感染。CRRT时间头孢他啶-阿维巴坦的PK/PD数据有限。一例病例陈诉自满当CVVH治疗剂量为2 L/h时,CRRT党羽孢他啶和阿维巴坦的吊销率分裂为57.1%和54.3%,给以头孢他啶-阿维巴坦1.25 g q8 h可达到PK/PD靶值(100%fT>MIC)[43]。一例病例陈诉自满当CVVHDF治疗剂量为2.75 L/h时,旧例剂量2.5 g q8 h可达到PK/PD靶值(fT>4×MIC)[44]。另1病例陈诉自满,当CVVHD治疗剂量为2 L/h时,头孢他啶-阿维巴坦2.5 g q12 h延迟输注2 h可使头孢他啶Cmin>4×MIC[45]。一项纳入8例难治性耐药铜绿假单胞菌感染病例的研究自满,当CVVHDF中位治疗剂量为38.6 ml·kg-1·h-1时,中位头孢他啶吊销率约为2.39 L/h,阿维巴坦吊销率为2.56 L/h,1.25~2.50 g q8 h捏续输注有益于完好意思头孢他啶游离稳态血药浓度/MIC≥4[46]。(3) 碳青霉烯类抗菌药物:保举主意11. CRRT不同形状下使用碳青霉烯类抗菌药物可参考肾功能浅薄患者的剂量给药。(保举级别:强保举)12. 对于MIC≤2 mg/L的病原菌感染,漠视CRRT时间给以亚胺培南剂量0.5 g q6 h;对于MIC 4~16 mg/L的病原菌感染,漠视给以1.0 g q6 h。(保举级别:强保举)13. 对于MIC=8 mg/L的病原菌感染,漠视CRRT时间给以好意思罗培南剂量2 g q8 h,必要时捏续输注或延迟输注3 h给药,或3~6 g qd捏续输注。(保举级别:弱保举)碳青霉烯类抗菌药物可被CRRT吊销。Meta分析研究自满,不同CRRT形状下AKI患者亚胺培南吊销率为89~149 ml/min,西司他丁吊销率为9~32 ml/min,漠视亚胺培南给药剂量为0.5 g q12 h至0.5 g q6 h[47]。CRRT治疗剂量与亚胺培南吊销率连接性研究论断尚不一致。前瞻性临床PK研究自满,CVVH高治疗剂量(32~74 ml·kg-1·h-1)下,亚胺培南吊销率更高[(3.27±0.48)L/h][48]。群体PK研究自满,跟着透析液流速增多,CRRT时间亚胺培南吊销率显耀增多[49]。而1项蒙特卡罗模拟分析研究发现,CRRT治疗剂量改变(20、37、74 ml·kg-1·h-1)与亚胺培南PK/PD靶值达标概率无临床连接性[50]。另外,病原菌的MIC亦然碳青霉烯类抗菌药物给药战略的迫切影响身分。早期研究自满CVVH或CVVHDF时间亚胺培南1 g qd足以治疗最常见的革兰阴性菌感染(MIC≤2 mg/L),而治疗MIC 4~8 mg/L的细菌感染可能需要2 g qd以上的给药剂量[51]。蒙特卡罗模拟分析研究自满,对于MIC≤2 mg/L的病原菌感染给以亚胺培南0.5 g q6 h,对于MIC 4~16 mg/L的病原菌感染给以亚胺培南1.0 g q6 h,可使PK/PD靶值(40%fT>MIC)达标概率≥80%[50]。基于不同CRRT治疗剂量、MIC、感染进程以及PK/PD靶值,好意思罗培南保举剂量在0.25 g q24 h至2.00 g q8 h波动[52-54]。在CVVH形状治疗剂量为20~40 ml·kg-1·h-1时,好意思罗培南1 g q12 h可在48 h内达到PK/PD靶值(≥60%fT>MIC),而好意思罗培南1 g q8 h可达到更高的PK/PD靶值(≥60%fT>4×MIC)[28]。在CVVHD或前稀释CVVH治疗剂量为25 ml·kg-1·h-1或35 ml·kg-1·h-1时,好意思罗培南0.75 g q8 h可达到PK/PD靶值(≥40%fT>4×MIC)[54]。基于亚洲东说念主群的PK模子指示,CVVH或CVVHD治疗剂量为20~25 ml·kg-1·h-1 或35 ml·kg-1·h-1时,对于MIC<2 mg/L的病原菌感染,好意思罗培南0.75 g q8 h可达到PK/PD靶值(≥40%fT>4×MIC)[55]。在CRRT时间,好意思罗培南捏续输注将会莳植PK/PD靶值达标率[56-58]。在CVVHDF形状(平均治疗剂量为37.4 ml·kg-1·h-1)下,好意思罗培南125~500 mg q6 h 捏续输注6 h可达到PK/PD靶值(游离稳态血药浓度/MIC>4)[59]。Meta分析研究自满,在CRRT治疗剂量为35 ml·kg-1·h-1的非创伤患者中,对于MIC≤4 mg/L的病原菌感染,给以好意思罗培南1 g q6 h或2 g q8 h~q6 h间歇输注,以及1 g q8 h延迟输注3 h或2 g qd捏续输注24 h可达到PK/PD靶值(100%fT>MIC);对于MIC=8 mg/L的病原菌感染,给以好意思罗培南2 g q8 h,或3~6 g qd捏续输注,可达到PK/PD靶值[60]。CRRT治疗剂量(25~50 ml·kg-1·h-1)对好意思罗培南达标概率无显耀影响[60]。2. 氨基糖苷类抗菌药物:保举主意14. 阿米卡星在CRRT时保举给以较高的负荷剂量,并延迟给药断绝,同期合股血药浓度监测进行剂量改变,防守Cmax/MIC在8~10之间。(保举级别:强保举)氨基糖苷类抗菌药物为浓度依赖性药物,需通过莳植Cmax/MIC赢得更佳的治疗遵守。在CVVHDF形状下给以首剂≥25 mg/kg 阿米卡星才智达到治疗峰值浓度[61]。最新蒙特卡罗模拟分析研究指示,接受CVVHDF的患者以Cmax/MIC>8为PK/PD靶值时,对于MIC≤4 mg/L的病原菌,阿米卡星负荷剂量25~30 mg/kg及给药断绝为24~48 h时可使首日及稳态PK/PD达标概率≥90%;对于MIC=4 mg/L的病原菌,阿米卡星负荷剂量15~20 mg/kg在首日无法完好意思PK/PD达标概率≥90%;而对于MIC≥8 mg/L的病原菌,给以阿米卡星15~30 mg/kg,给药断绝为24 h、36 h或48 h时均无法完好意思PK/PD达标概率≥90%[62]。在CVVH形状下相通保举给以较高的负荷剂量和延迟给药断绝(25 mg/kg q48 h),合股血药浓度监测进行阿米卡星剂量改变[63]。在CVVHD时间,阿米卡星Cmax和半衰期变异泛泛[64],弗成根据透析剂量或其他身分准确规划阿米卡星的给药有筹算,应根据首剂PK对接受CVVHD的患者制定个体化的给药有筹算。研讨到氨基糖苷类药物的治疗窗较窄,热烈漠视根据血药浓度监测进行充分且安全的剂量改变,漠视防守Cmax/MIC在8~10之间[15]。3. 喹诺酮类抗菌药物:保举主意15. 主要经肾脏吊销的喹诺酮类药物在CRRT时间吊销率有所增多,因此需要相应增多剂量。(保举级别:弱保举)16. 重症感染时,环丙沙星在CVVH或CVVHDF形状下漠视400 mg q8 h,CVVHD形状下漠视200 mg q8 h。(保举级别:弱保举)17. 对于敏锐的革兰阳性菌感染,在CVVH或CVVHD形状下,CRRT治疗剂量为25 ml·kg-1·h-1或30 ml·kg-1·h-1时,漠视给以左氧氟沙星500~750 mg qd。(保举级别:弱保举)18. 莫西沙星经肝肾双通说念道路吊销,在CRRT时间无需改变剂量。(保举级别:强保举)环丙沙星可被CRRT吊销[65-66]。在CVVH和CVVHDF时间环丙沙星的吊销是可变的且具有较低的体外吊销分数。早期研究标明,当CVVHD透析液流速为3 L/h时,环丙沙星200 mg q8 h是适合的剂量[67]。在CVVHDF形状下,CRRT治疗剂量为4 L/h时,对于MIC≤0.5 mg/L的病原菌感染,需要环丙沙星400 mg q12 h才智达到PK/PD靶值;在CVVH、CVVHDF或CVVHD形状下,CRRT治疗剂量为30 ml·kg-1·h-1或更高时,可能需要400 mg q8 h或更高的环丙沙星剂量[68-69]。保举使用血药浓度监测进行剂量改变。与环丙沙星比拟,左氧氟沙星Vd较小,因此具有较高的体外吊销分数。早期研究标明,在CRRT低治疗剂量下,接受CVVH或CVVHDF的患者可使用左氧氟沙星250 mg qd抗感染[70]。最新蒙特卡罗模拟研究发现,在CVVH或CVVHD形状下,使用CRRT高治疗剂量(25 ml·kg-1·h-1或30 ml·kg-1·h-1),对于MIC=2 mg/L的铜绿假单胞菌感染,左氧氟沙星旧例给药有筹算均未达到PK/PD靶值(治疗前72 h的日平均AUC/MIC≥125);而对于MIC=2 mg/L的肺炎链球菌感染,左氧氟沙星750 mg qd可达到PK/PD靶值(治疗前72 h的日平均AUC/MIC≥50),因此左氧氟沙星不应行为单一疗法用于治疗CRRT患者的严重铜绿假单胞菌感染[71]。莫西沙星经肝肾双通说念吊销,在接受CVVHD或血液透析患者中其PK参数与肾功能浅薄患者接近[72-73],因此CRRT时间无需改变剂量。4. 糖肽类抗菌药物:保举主意19. 与肾功能浅薄患者剂量比拟,永劫霉素和替考拉宁在CRRT时间漠视减少给药剂量。(保举级别:强保举)20. 在CVVH形状下,漠视永劫霉素给以负荷剂量20 mg/kg,防守剂量500 mg q8 h;在CVVHDF形状下,漠视永劫霉素给以负荷剂量20 mg/kg,防守剂量500 mg q12 h。根据血药浓度监测限定改变剂量,防守稳态Cmin在10~20 mg/L,或AUC0~24 h/MIC在400~600。(保举级别:强保举)21. CRRT时漠视替考拉宁给以负荷剂量10~12 mg/kg q12 h(相连2 d),第3天起给以10~12 mg/kg q72 h。对于非复杂抗甲氧西林金黄色葡萄球菌感染,保举贪图Cmin为15~30 mg/L;对于严重和/或复杂性抗甲氧西林金黄色葡萄球菌感染(如心内膜炎、骨髓炎),保举贪图Cmin为20~40 mg/L。保举根据血药浓度监测限定改变剂量。(保举级别:强保举)永劫霉素和替考拉宁均具有较大的分子量,与普通血液透析比拟,CRRT可增多此类药物的体外吊销[74]。在CVVH治疗剂量为0.8~1.2 L/h时,给以永劫霉素1 g q12 h,约49.4%±20.8%的永劫霉素可经CVVH吊销,给以500~750 mg q12 h可使稳态Cmin防守在15~20 mg/L[75]。一项前瞻性研究自满,当CVVH治疗剂量为30~40 ml·kg-1·h-1时,给以永劫霉素500 mg q12 h,约66.96%±6.05%的永劫霉素可经CVVH吊销,给以400~650 mg q12 h可使稳态Cmin防守在15~20 mg/L[76]。另1项回归性研究发现,在较高治疗剂量的CVVH形状[置换液流速(31.3±12.0)ml·kg-1·h-1]下,给以永劫霉素15~22 mg/kg q12 h~24 h更有助于达到Cmin(15~20 mg/L)[77]。与CVVH形状比拟,CVVHD形状对永劫霉素的吊销较低。一项纳入160例患者的单中心回归性队伍研究发现,在CVVHD治疗剂量为1.5~2.0 L/h(19.1~26.4 ml·kg-1·h-1)下,永劫霉素给药日剂量为1.0~1.5 g(11.1~14.8 mg/kg)时,患者平均Cmin为24.6 mg/L,推断永劫霉素10 mg/kg qd可能是CVVHD形状下较为适合的给药剂量[78]。2013年日本化疗学会和日本治疗药物监测学会保举在CVVHDF形状下给以永劫霉素负荷剂量15~20 mg/kg,防守剂量500 mg(7.5~10.0 mg/kg)qd[79]。一项蒙特卡罗模拟分析研究自满,对于接受CVVHDF的危重症患者,给以负荷剂量2 g,防守剂量750 mg q12 h可使永劫霉素Cmin在15~20 mg/L[80]。而MIC≥1 mg/L的CRRT感染患者可能需要永劫霉素总剂量≥2.75 g qd才可达到灵验的治疗浓度[81]。好意思国卫生系统药剂师协会、好意思国感染病学会最新指南保举在CRRT治疗剂量为20~25 ml·kg-1·h-1时,保举永劫霉素开动防守剂量为7.5~10.0 mg/kg q12 h[82]。最新蒙特卡罗模拟分析研究觉得不同CRRT形状对永劫霉素PK/PD靶值达标概率无显耀影响,保举在CRRT治疗剂量≤30 ml·kg-1·h-1时给以永劫霉素负荷剂量20 mg/kg,防守剂量500 mg q8 h;在CRRT治疗剂量为35 ml·kg-1·h-1时,增多防守剂量为1 g q12 h[83]。另1项蒙特卡罗模拟分析研究保举,在CRRT治疗剂量为20~25 ml·kg-1·h-1或25.1~45.0 ml·kg-1·h-1时,保举永劫霉素剂量分裂为5.0 mg/kg q12 h或7.5 mg/kg q12 h[84]。由于在CRRT时间患者使用永劫霉素AUC各异大,且永劫霉素吊销受CRRT治疗剂量的显耀影响,现时尚无长入的剂量保举,漠视根据血药浓度监测限定调整个这个词体剂量使稳态Cmin防守在10~20 mg/L或AUC0~24 h/MIC防守在400~600[82]。替考拉宁相通主要由肾脏吊销,体表里研究发现替考拉宁可被聚甲基丙烯酸甲酯膜或高通量聚砜膜等膜吸附[85-86]。在CVVH形状下保举替考拉宁的负荷剂量为1 200 mg,防守剂量为600~1 800 mg qd[87]。早期研究标明,在CVVHD形状下,替考拉宁负荷剂量为800 mg,防守剂量为400 mg q48 h~72 h[88]。现时研究发现,即使在CRRT低治疗剂量下(CVVHDF形状,治疗剂量<20 mg·kg-1·h-1),在前3日给以4剂12 mg/kg负荷剂量(第1日12 mg/kg q12 h,第2、3日12 mg/kg qd)亦完好意思Cmin≥20 mg/L[89]。蒙特卡罗模拟分析研究自满,替考拉宁给以负荷剂量10 mg/kg q12 h (相连2 d)可在多样CRRT形状下达到Cmin>15 mg/L[83]。2022年日本化疗学会和日本治疗药物监测学会漠视在CVVHDF形状下,如需达到Cmin 15~30 mg/L,需在开动3 d给以10 mg/kg替考拉宁,其中第1天给药2次,第2、3天各给药1次;如需达到Cmin 20~40 mg/L,需在开动3 d给以12 mg/kg替考拉宁,其中第1天给药2次,第2、3天各给药1次;防守剂量可研讨给以替考拉宁3.0~3.3 mg/kg qd[90]。咱们漠视对替考拉宁进行血药浓度监测,非复杂抗甲氧西林金黄色葡萄球菌感染患者的保举贪图Cmin为15~30 mg/L。对于严重和/或复杂性抗甲氧西林金黄色葡萄球菌感染(如心内膜炎、骨髓炎)患者,替考拉宁的保举贪图Cmin为20~40 mg/L[91]。5. 环脂肽类抗菌药物:保举主意22. 在CRRT治疗剂量≤25 ml·kg-1·h-1时,漠视达托霉素给药剂量为6~8 mg/kg qd,而在治疗剂量30~35 ml·kg-1·h-1 下,漠视给药剂量为8~10 mg/kg qd。(保举级别:强保举)达托霉素为环脂肽类抗菌药物。在CRRT治疗剂量为30~40 ml·kg-1·h-1下,给以达托霉素3~8 mg·kg-1·h-1后患者体内药物自满量与肾功能浅薄的重症监护病房患者相似,但低于健康志愿者[92]。在CVVHDF或CVVHD(CRRT治疗剂量为30~40 ml·kg-1·h-1)形状下,使用6 mg/kg qd的达托霉素莫得发生显耀的蓄积[93]。也有研究自满对于金黄色葡萄球菌菌血症或右心内膜炎感染患者,较大的给药剂量有筹算(8 mg/kg qd)适用于CVVHDF患者[94]。关联词,研究发现,8 mg/kg qd达托霉素很有可能达到毒性阈值,而6 mg/kg qd在CVVHD或CVVHDF时间提供了令东说念主得志的风险-收益均衡[95]。针起义甲氧西林金黄色葡萄球菌感染,1项以达托霉素Cmin≥3.2 mg/L及AUC0~24 h/MIC≥1 061 为PK/PD靶值的蒙特卡罗模拟分析研究自满,CRRT治疗剂量≤25 ml·kg-1·h-1时,达托霉素给药的保举有筹算为6~8 mg/kg qd,而在30~35 ml·kg-1·h-1下保举给药8~10 mg/kg qd[83]。6. 噁唑烷酮类抗菌药物:保举主意23. CRRT时间旧例无需改变利奈唑胺剂量,研讨到患者个体各异较大,保举通过血药浓度监测进行剂量改变,使稳态Cmin防守在2~8 mg/L。(保举级别:强保举)时常觉得利奈唑胺经肾脏吊销较少,肾功能不全患者无需改变剂量。关联词1项系统评价研究发现,接受CRRT的AKI脓毒症重症患者的利奈唑胺PK/PD参数存在很大各异[96]。海外研究自满对于存在残余肾功能的患者,利奈唑胺900 mg q8 h有很高的治疗生效概率,而不会影响CVVHD或CVVHDF的安全性[97]。保举给与血药浓度监测来莳植CRRT时利奈唑胺治疗的灵验性[98],漠视防守稳态Cmin在2~8 mg/L[16]。7. 替加环素:保举主意24. CRRT时间旧例无需改变替加环素剂量。(保举级别:强保举)替加环素经肝肾双通说念吊销,研究标明,与总吊销率比拟(18.3 L/h),CRRT对替加环素的吊销孝顺较小,在CVVHD和CVVHDF形状下吊销率分裂为1.69 L/h和2.71 L/h,与非AKI患者肾脏吊销率接近[99]。一项前瞻性研究自满,非CRRT组替加环素Cmax、Cmin和AUC0~24 h分裂为(1.00±0.66)mg/L、(0.20±0.12)mg/L和(22.12±14.46)mg·h·L-1,CRRT组Cmax、Cmin和AUC0~24 h分裂为(0.96±0.31)mg/L、(0.22±0.12)mg/L和(19.90±8.14)mg·h·L-1,2组PK/PD参数各异均无统计学好奇景仰[100]。在CVVHDF形状下,CRRT组和非CRRT组替加环素Cmax无显耀各异,而Cmin显耀高于非CRRT组,但未达到毒性阈值[101]。因此CRRT时间无需改变替加环素给药剂量。8. 多黏菌素类抗菌药物:保举主意25. 多黏菌素E甲磺酸钠(colistimethate sodium,CMS)在CRRT时间保举给以负荷剂量2×平均稳态血药浓度(Css,avg)[mg/kg,以多黏菌素E活性基质(colistin base activity,CBA)计],12~24 h后给以防守剂量,其中CVVHDF形状给以CBA 220 mg q12 h,CVVH和CVVHD形状给以逐日剂量192×Css,avg(mg,以CBA计),每8~12小时给药1次,并根据血药浓度监测限定改变剂量,使多黏菌素E Css,avg达到2 mg/L或24 h稳态血药浓度-时辰弧线底下积(AUCss,24 h)达到50 mg·h·L-1。(保举级别:弱保举)CMS是黏菌素的前药,主要经肾脏吊销,在体内转换为CBA起效,因此CRRT对CMS的PK有显耀影响。与肾功能浅薄患者比拟,接受CRRT的患者对黏菌素吊销赫然,因此需要更大剂量的CMS。案例研究自满,3例接受CVVHDF的患者透析液流速分裂为1.90、2.30、1.95 L/h,CMS剂量分裂为150 mg q18 h、75 mg q8 h、75 mg q8 h,其吊销半衰期分裂为15.7、8.0、7.7 h,通过CVVHDF的吊销率分裂为0.67、0.81、0.71 L/h,分裂占总的体外吊销率的35%、45%、36%,总的体外吊销率分裂占总吊销率的59%、43%、45%[102]。对于CVVHDF患者,唯唯一部分体外吊销由透析滤过引起,还有一部分可能通过滤膜吸附而丢失[102]。一项多中心群体PK研究自满,CMS和CBA不错被血液透析灵验吊销,CVVHD(透析液流速为42 ml/min)形状下的吊销率为2.06 L/h[103]。该研究漠视对于接受CVVHD的患者,可根据体重先给以负荷剂量,即CBA(mg)=Css,avg(mg/L)×2×体重(kg)(注:Css,avg根据MIC、感染部位、感染严重进程坚信,时常给与2 mg/L;体重采用理思体重和内容体重中的最低值;负荷剂量>300 mg时需慎用);12~24 h后给以防守剂量,即CBA逐日防守剂量(mg)=192×Css,avg,每8~12小时给药1次[103]。一项纳入8例CVVHDF危重症患者的研究自满,给药后6 h CBA Css,avg为1.72 mg/L,CVVHDF对黏菌素的吊销率特别于总吊销率的62%,根据CMS-CBA血药浓度的PK规划模子,该研究觉得给以CVVHDF患者首剂负荷剂量CMS 1 200万单元(CBA 396 mg)、防守剂量650~750万单元(CBA 214.5~247.5 mg)q12 h的有筹算较为适合,但其安全性可能有待评估[104]。2019年1项针对CVVH形状下使用CMS的呼吸机连接性肺炎患者的回归性不雅察性队伍研究自满,CRRT治疗剂量为35 ml·kg-1·h-1时给以CMS负荷剂量900万单元(CBA 297.0 mg),防守剂量450万单元(CBA 148.5 mg)q8 h,约64%患者有高超的治疗遵守,其余患者治疗失败[105]。玄虚现时的研究,CRRT不错灵验吊销CMS和CBA,均漠视给以首剂负荷剂量,有助于更快地达到贪图黏菌素浓度,24 h后给以防守剂量。多黏菌素最好使用国际共鸣指南漠视对于接受CRRT的患者,给以CBA 220 mg q12 h,以使黏菌素Css,avg达到2 mg/L[15]。保举主意26. 多黏菌素B在CRRT时间原则上不需要改变剂量,保举旧例进行血药浓度监测,使多黏菌素B Css,avg达到2~4 mg/L或AUCss,24 h达到50~100 mg·h·L-1。(保举级别:强保举)硫酸多黏菌素E和多黏菌素B主要通过非肾道路吊销,在CRRT时间表面上不需要改变剂量。研究标明,多黏菌素B在CVVHD(透析液流速1.8~2.0 L/h)形状下的吊销率仅占总吊销率的5.62%~12.20%,通过CVVHD的吊销率为0.001 5~0.005 2 L·h-1·kg-1,指示多黏菌素B弗成通过CRRT灵验吊销,无需改变剂量[106]。基于此,多黏菌素最好使用国际指南漠视行CRRT时使用多黏菌素B无需改变剂量[15]。然而比年有针对中国东说念主群的PK/PD数据发现,CRRT可能也会吊销多黏菌素B。一项基于中国危重症患者使用多黏菌素B的群体PK模子研究自满,CRRT是吊销率的迫切协变量,未接受CVVH患者的AUCss,24 h平均值约为CVVH患者的3倍[107]。近期另1项基于中国危重症患者使用多黏菌素B的PK/PD研究相通自满CRRT对多黏菌素B的吊销率赫然高于非CRRT,CRRT的AUC0~12 h赫然低于非CRRT患者,且CVVH和CVVHDF之间的AUC0~12 h无赫然各异[108]。基于前瞻性研究的PK模子分析相通发现CVVHDF可莳植多黏菌素B的吊销率[109]。上述研究指示多黏菌素B在CVVH或CVVHDF形状下也可能被显耀吊销。而近期1项研究发现,与肾功能保留患者比拟,接受CVVHD(平均治疗剂量为29 ml·kg-1·h-1)的患者具有较高的多黏菌素B自满量[110]。因此漠视在血药浓度监测要求下改变剂量,以使多黏菌素B Css,avg达到2~4 mg/L。硫酸黏菌素尚缺少CRRT连接研究,基于其主要经非肾道路吊销,推断在CRRT时间原则上不需要改变剂量。9. 磺胺类抗菌药物:保举主意27. 在CVVH或CVVHD形状下,CRRT治疗剂量在1~6 L/h时,可研讨以甲氧苄啶(trimethoprim,TMP)10 mg/kg qd,分2次给药,并进行血药浓度监测,治疗耶氏肺孢子菌肺炎时防守磺胺甲噁唑(sulfamethoxazole,SMZ)Cmax在100~200 mg/L。(保举级别:弱保举)SMZ-TMP主要从尿液中排出。案例研究自满,在CVVHDF形状下静脉用SMZ-TMP可被显耀吊销[111]。CVVHDF中的SMZ吊销施展出高度可变性,无明确保举剂量。TMP的跨膜吊销率大于SMZ。体外研究自满,CVVH或CVVHD形状下,CRRT治疗剂量在1~6 L/h时,给以TMP 10 mg/kg qd使稳态Cmax防守在5~10 mg/L,给以SMZ 50 mg/kg qd使稳态Cmax防守在100~200 mg/L,对于耶氏肺孢子菌具有较好的抗菌遵守[112]。(二)抗真菌药物1. 唑类抗真菌药物:保举主意28. CVVH治疗剂量为2 L/h时,漠视给以氟康唑200~400 mg qd;CVVHD治疗剂量为2 L/h和4 L/h时,漠视分裂给以氟康唑400~800 mg qd和600 mg q12 h;CVVHDF治疗剂量为2~3 L/h时,如病原菌MIC≤8 mg/L,漠视给以氟康唑400~800 mg qd,如病原菌MIC为8~16 mg/L,漠视给以氟康唑800 mg qd。(保举级别:强保举)唑类抗真菌药物由于其吊销机制各异,CRRT时间剂量改变战略存在各异。约莫80%的氟康唑以原形药物通过尿液排出。在CRRT时间,氟康唑可被灵验吊销。早期研究标明,在CRRT治疗剂量为2 L/h时,氟康唑800 mg qd的剂量适用于接受CVVHD或CVVHDF的患者,而氟康唑400 mg qd的剂量适用于接受CVVH的患者,对于非克柔念珠菌或光滑念珠菌感染且MIC≤8 mg/L时,氟康唑逐日剂量可降至400 mg(CVVHD或CVVHDF)或200 mg(CVVH)[24]。血液透析时间保举的治疗剂量高于血液滤过,其原因可能是氟康唑的低分子量和低卵白合股率使其较容易通过扩散穿过滤器。跟着CRRT治疗剂量增多,氟康唑吊销对应增多。一例病例陈诉自满在CVVHD高治疗剂量(4 L/h)下,更高的氟康唑剂量(负荷剂量900 mg,防守剂量600 mg q12 h)可达到贪图浓度(AUC0~24 h/MIC≥100,Cmax 16~32 mg/L,Cmin 10 mg/L)[113]。一例痴肥病例陈诉标明,在CVVH治疗剂量为2.4~3.2 L/h时,6 mg/kg qd的氟康唑剂量粗略完好意思PK/PD靶值(AUC/MIC≥25)[114]。一项纳入10例重症无尿患者的研究发现,在CVVHDF形状透析液流速1 L/h、滤过液流速2 L/h要求下,CVVHDF的体外吊销率约占氟康唑总吊销率的62%[115]。以AUC/MIC>25为氟康唑PK/PD靶值,进一步给与蒙特卡罗模拟分析,限定自满,针对MIC为1 mg/L和4 mg/L的真菌感染,氟康唑负荷剂量400 mg 和1 600 mg可在开动12 h达到PK/PD靶值;达到稳态后对于MIC≤8 mg/L的真菌感染,氟康唑200 mg bid与400 mg bid 给药有筹算PK/PD靶值达标概率接近,而对于MIC 8~16 mg/L的真菌感染,氟康唑400 mg bid具有更高的PK/PD靶值达标概率[115]。在氟康唑剂量改变时间,应试虑病原菌的MIC、CRRT神气、CRRT治疗剂量以及感染部位。保举主意29. 在CRRT时间无需改变口服伏立康唑、口服泊沙康唑、口服及打针艾沙康唑的给药剂量。接受CRRT的患者可参照肾功能浅薄患者使用伏立康唑打针剂及泊沙康唑打针剂,漠视优先遴荐口服制剂。(保举级别:强保举)由于伏立康唑经非肾道路吊销,在CRRT时间伏立康唑的口服制剂不需要改变剂量。泊沙康唑主要经粪便排出,口服制剂相通无需改变剂量。PK案例研究标明,在CVVHDF时间,静脉使用泊沙康唑的患者未出现泊沙康唑蓄积[116]。伏立康唑和泊沙康唑静脉制剂辅料为磺丁基醚-β-环糊精,可在肾功能受损的患者体内蕴蓄。对于接受伏立康唑打针剂[117]或泊沙康唑打针剂[118]治疗的患者,CVVH可灵验吊销其体内的磺丁基醚-β-环糊精。艾沙康唑代谢后经粪便及尿液吊销,原形药物经肾脏吊销<1%,研究发现艾沙康唑不易被CRRT吊销,无需改变剂量[119]。2. 棘白菌素类抗真菌药物:保举主意30. 在CRRT时间,棘白菌素类抗菌药物(卡泊芬净和米卡芬净)无需改变给药剂量。(保举级别:强保举)棘白菌素类药物,主要包括卡泊芬净和米卡芬净,在体内经肝脏代谢后代谢居品经粪便及尿液排出。现存研究觉得卡泊芬净和米卡芬净在不同CRRT形状下自满量无显耀各异,接受任何一种CRRT形状的患者都不需要改变卡泊芬净剂量[120-122]。但也有研究标明,CRRT滤器对于卡泊芬净及米卡芬净存在吸附作用[123-124],可能导致药物亏蚀,其临床好奇景仰尚需进一步阐述。3. 多烯类抗真菌药物:保举主意31. 在CRRT时间,两性霉素B脂质体无需改变给药剂量。(保举级别:弱保举)两性霉素B在体内经肾脏逐渐吊销,而其脂质体在肾组织浓度低,呈非线性吊销。现存研究标明,CVVH和CVVHDF对两性霉素B脂质体PK参数无显耀影响[125-126]。一项不雅察性研究自满,对于接受CRRT的患者,两性霉素B脂质体给药剂量和频次均无需改变[127]。现时缺少两性霉素B脱氧胆酸盐、两性霉素B胆固醇硫酸酯复合物在CRRT时间的剂量研究,基于其PK特征,推断无需改变剂量。六、CRRT特别情况下抗菌药物改变战略保举主意32. 对于24 h无尿行CRRT患者,在使用主要经肾脏吊销的抗菌药物时,如转为间歇性肾替代治疗,需驻扎减少剂量,并在透析收尾后给药。(保举级别:强保举)33. 有残余肾功能患者行CRRT时间,使用主要经肾脏吊销的抗菌药物,需研讨根据残余肾功能情况增多剂量,在达到牢固血药浓度前漠视监测血药浓度。(保举级别:强保举)24 h无尿且行CRRT患者,如行间歇性肾替代治疗以及存在残余肾功能,抗菌药物剂量需进行对应改变。对于主要经肾脏吊销的抗菌药物,如患者逐日行固定时辰的CRRT,保举鄙人机后给以抗菌药物,同期应根据治疗时辰及肾功能对应改变抗菌药物剂量,给药剂量应低于行CRRT时的剂量,延迟停机时辰可能需要对应镌汰剂量或罢手治疗[7]。对于CRRT患者转血液透析治疗后,应试虑将抗菌药物剂量改变为血液透析治疗时的给药剂量,大多数抗菌药物应在透析当日透析后给药。与接受CRRT的无尿患者比拟,存在残余肾功能且接受CRRT的患者经肾脏吊销药物吊销率增多[7],需同期研讨CRRT及残余肾功能对药物的吊销作用,应参考CRRT治疗剂量及肌酐吊销率,对应增多抗菌药物剂量。声明 编制本共鸣时邀请了药学大家及各连接学科临床大家对所罕有据进行了审议。然而由于此类数据可能会随时发生变化,因此咱们无法确保其在使用时的准确性,医生应根据其专科学问讲求解释和应用所罕有据。出书方不合在本文献指引下作念出的任何医疗卫生活动承担任何法律背负,也不合未经授权使用本文献的任何其他使用方承担任何法律背负志谢 感谢以下大家在共鸣制定中的匡助(按姓名汉语拼音字母表法例排序):曹恒斌(湖州市中心病院)、戴单单(宁波大学附庸第一病院)、胡阳敏(浙江大学医学院附庸第二病院)、李晴宇(杭州市肿瘤病院)、林彬(长兴县东说念主民病院)、芦小燕(宁波华好意思病院)、毛小红(浙江省东说念主民病院)、吴娇芬(宁波市医疗中心李惠利病院)、项迎春(浙江病院)、俞振伟(浙江大学医学院附庸邵逸夫病院)、詹波涛(金华市中心病院)、张春红(温州大学医学院附庸第一病院)、张萍(浙江大学医学院附庸第一病院)、郑霞(浙江大学医学院附庸第一病院)、周志慧(浙江大学医学院附庸邵逸夫病院)、朱剑萍(浙江大学医学院附庸邵逸夫病院)利益突破 整个作家声明无利益突破相连性肾替代治疗抗菌药物剂量改变共鸣大家组大家组组长:卢晓阳(浙江大学医学院附庸第一病院临床药学部)、康焰(四川大学华西病院重症医学科)、俞云松(浙江省东说念主民病院感染科)、陈崴(中山大学附庸第一病院肾内科)、张玉(华中科技大学同济医学院附庸协和病院药学部)、蔡急流(浙江大学医学院附庸第一病院重症医学科)大家组布告:姜赛平(浙江大学医学院附庸第一病院临床药学部)大家构成员(按姓名汉语拼音字母表法例排序):蔡急流(浙江大学医学院附庸第一病院重症医学科)、陈杰(中山大学附庸第一病院药学部)、陈崴(中山大学附庸第一病院肾内科)、陈勇川(陆军军医大学第一附庸病院药物临床进修机构办公室)、董亚琳(西安交通大学第一附庸病院科技部)、方巍(山东省立病院重症医学科)、郭玉金(济宁市第一东说念主民病院临床药学科)、韩飞(浙江大学医学院附庸第一病院肾脏病中心)、黄品芳(福建医科大学附庸第一病院药学部)、姜玲[中国科学时期大学附庸第一病院(安徽省立病院)药学部]、江荣林(浙江省中病院重症医学科)、康焰(四川大学华西病院重症医学科)、李文雄(都门医科大学附庸北京向阳病院外科重症监护病房)、卢晓阳(浙江大学医学院附庸第一病院临床药学部)、马晓春(中国医科大学第一病院重症医学科)、邵华(东南大学附庸中大病院药学部)、邵敏(安徽医科大学第一附庸病院重症医学科)、史琛(华中科技大学同济医学院附庸协和病院药学部)、王建华(新疆医科大学第一附庸病院药学部)、王婧雯(西药学部)、肖永红(浙江大学医学院附庸第一病院传染病诊治国度要点实验室)、熊爱珍(南昌大学附庸第二病院药学部)、熊滨(广西壮族自治区东说念主民病院重症医学科)、徐萍(中南大学湘雅二院药学部)、徐永昊(广州呼吸健康研究院重症医学科)、杨毅(浙江大学医学院附庸第四病院肾病科)、杨勇(四川省东说念主民病院药学部)、俞云松(浙江省东说念主民病院感染科)、曾振国(南昌大学第一附庸病院重症医学科)、张波(北京协和病院药学部)、张菁(复旦大学附庸华山病院抗生素研究所)、张丽娜(中南大学湘雅病院重症医学科)、张弋(天津市第一中心病院药学部)、张玉(华中科技大学同济医学院附庸协和病院药学部)、赵鸣雁(哈尔滨医科大学附庸第一病院重症医学科)、郑波(北京大学第一病院临床药理研究所)、郑瑞强(江苏省苏北东说念主民病院重症医学科)主要援笔大家:李璐(浙江大学医学院附庸第一病院临床药学部)、王融溶(浙江大学医学院附庸第一病院临床药学部)共同援笔大家:李佳(中山大学附庸第一病院药学部)、李馨(吉林大学第二病院药品处理部)、梁培(南京饱读楼病院药学部)、褚燕琦(都门医科大学宣武病院药学部)、俞文桥(浙江大学医学院附庸第一病院重症医学科)要领学大家:金明娟(浙江大学公卫学院)图片 迪丽热巴换脸1. 国度卫生健康委办公厅. 对于印发血液净化标准操作规程(2021版)的示知[EB/OL]. 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Correction to: the clinical usage of liposomal amphotericin B in patients receiving renal replacement therapy in Japan: a nationwide observational study[J]. Clin Exp Nephrol, 2021, 25(3): 288. DOI: 10.1007/s10157-020-02004-5.图片 援用本文: 相连性肾替代治疗抗菌药物剂量改变共鸣大家组, 中国药学会病院药学专科委员会, 中国医药说明协会感染疾病专科委员会. 相连性肾替代治疗抗菌药物剂量改变大家共鸣(2024年版)[J]. 中华肾脏病杂志, 2024, 40(2): 158-174. DOI: 10.3760/cma.j.cn441217-20230906-00906.著作编号:1001-7097(2024)02-0158-17收稿日历:2023-09-06出书日历:2024-02-15网刊发布日历:2024-02-20本文剪辑:彭苗 本站仅提供存储作事,整个内容均由用户发布,如发现存害或侵权内容,请点击举报。 |