儿童连续性肾替代治疗期间抗菌药物治疗方案调整专家共识（2026）

1 共识形成方法

本共识由药学、儿童重症医学、儿童肾脏病学、新生儿及循证医学等多学科专家组成编写委员会。编写组系统检索了 PubMed、Web of Science、Embase、Cochrane Library、万方医学网、中国知网等数据库(截至2025年8月31日)。检索关键词为:儿童、连续性肾替代治疗、群体药代动力学、药代动力学、治疗药物监测等(包括对应的英文关键词)。经筛选,共纳入167篇文献,包括群体药代动力学(population pharmacokinetics, PopPK)研究66篇,PK研究39篇及临床病例报告6篇等。基于文献证据与临床经验,起草形成初步推荐意见。随后采用改良 Delphi 咨询法进行2轮投票(共39位专家参与投票)。推荐强度依据1~10分制评分均值确定:8~10分为“强推荐”,5~7分为“弱推荐”,1~4分为“不推荐”。关于治疗药物监测(therapeutic drug monitoring, TDM)推荐部分,6~10分为推荐常规监测,1~5分为鼓励医疗机构监测。所有条目经多轮讨论直至达成共识。

2 CRRT期间影响抗菌药物方案的主要因素

CRRT是一组通过不同机制清除水分和溶质的治疗模式总称。患儿接受CRRT治疗期间抗菌药物的合理应用需要基于CRRT因素、药物因素以及患儿因素进行综合评估。

2.1 CRRT因素在制定 CRRT患儿抗菌药物治疗方

表1 不同 CRRT 模式清除溶质的原理与特点

Table 1 The principles and characteristics of different CRRT modes in solute clearance

|清除机制|驱动因素|适用模式|优势分子量范围(Da)|置换液和透析液| |---|---|---|---|---| |对流|跨膜压|SCUF, CVVH|中、小分子(500~5000)|SCUF 无需置换液或透析液, CVVH 需补充置换液| |弥散|浓度梯度差|CVVHD|小分子(<500)|需使用透析液| |对流+弥散|跨膜压+浓度梯度差|CVVHDF|中、小分子(<5000)|需同时使用置换液和透析液|

注:CRRT:连续性肾替代治疗;SCUF:缓慢连续性超滤;CVVH:持续静脉-静脉血液滤过;CVVHD:持续静脉-静脉血液透析;CVVHDF:持续静脉-静脉血液透析滤过;SCUF虽属对流,但因超滤量极低,溶质清除可忽略 CRRT:continuous renal replacement therapy;SCUF:slow continuous ultrafiltration;CVVH:continuous venovenous hemofiltration;CVVHD:continuous venovenous hemodialysis;CVVHDF:continuous venovenous hemodiafiltration;although SCUF operates on the principle of convection, its solute clearance is negligible due to the extremely low ultrafiltration rate

案时,需要综合考虑所采用的CRRT模式、滤器类型及治疗参数对PK的影响[1]。

2.1.1 CRRT模式 目前CRRT主要治疗模式包括持续静脉-静脉血液滤过(continuous venovenous hemofiltration, CVVH)、持续静脉-静脉血液透析(continuous venovenous hemodialysis, CVVHD)、持续静脉-静脉血液透析滤过(continuous venovenous hemodiafiltration, CVVHDF)和缓慢连续性超滤(slow continuous ultrafiltration, SCUF)。研究显示,不同模式的药物清除效率为 CVVHDF> CVVHD>CVVH>SCUF[2],其原理和特点见表1。

2.1.2 CRRT 滤器 药物通过滤器的能力可通过2个关键参数评估:筛分系数(sieving coefficient, SC)和饱和系数(saturation coefficient, SA)。二者分别定义为超滤液和透析液中溶质浓度与血液溶质浓度的比值。不同滤膜通透性有差异,与低通量膜相比,高通量膜对大分子药物的通透性更大,临床 CRRT 多采用高通量膜,但目前仍缺乏基于滤器特性的精准剂量调整建议。

2.1.3 置换液补充形式与 CRRT 治疗剂量 置换液的补充形式可分为前稀释与后稀释,前稀释清除效率较后稀释模式下降[3]。两种模式对药物清除的影响见表2。

CRRT 治疗剂量由透析液流速($Q_d$)、置换液流速($Q_f$)与超滤液流速($Q_f$)共同决定。2012年改善全球肾脏病预后组织(Kidney Disease: Improving Global Outcomes, KDIGO)指南建议 CRRT 患者接受20~25 mL/(kg·h)的治疗剂量[4]。不同模式 CRRT 的清除率(clearance, CL)计算方法不同,目前儿童与成人 CRRT 时药物 CL 计算公式相似[5]。但仅凭流速调整 CRRT 治疗剂量往往难以达到理想的药效动力学(pharmacodynamics, PD)靶值,制定治疗方案时需综合考量多种因素。

2.2 药物因素 CRRT 期间抗菌药物治疗方案调整需综合考虑药物物理化特性(附录A),影响药物清除的关键因素、指标及趋势见表3[3,5-11]。

2.3 患儿因素 CRRT期间,患儿PK特征,如分布容积(volume of distribution, $Vd)^{[7-8]}$、蛋白结合率、消除半衰期($T_{1/2}$)等会因多种临床因素(如高炎症状态$^{[12]}$)发生显著变化,主要表现及原因见表4,CRRT期间治疗方案调整的流程见图1。

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Table 2 Effects of two replacement fluid administration modes on drug clearance

|项目|前稀释模式|后稀释模式| |---|---|---| |作用特点|置换液在滤器前与血流混合, 稀释血浆药物浓度|置换液在滤器后加入, 血浆直接进入滤器| |清除效率|较后稀释下降|药物CL与流速和SC相关| |CL计算公式|$ \text{超滤率}\times\text{SC}\times(1-\frac{Q_r}{\text{血流速}+Q_r}) $|超滤率×SC|

注:CL:清除率;SC:筛分系数;$Q_r$:置换液流速 CL:clearance;SC:sieving coefficient;$Q_r$:replacement flow rate

Table 3 Physicochemical properties of drugs influencing CRRT regimen djustments

|关键因素|关键指标|影响| |---|---|---| |分子量特性[6]|药物分子量|<500 Da 通过弥散作用清除;500~5000 Da 通过对流方式清除| |蛋白结合特性|蛋白结合率|危重症患儿常伴低蛋白血症,可显著降低药物蛋白结合率,增加清除[3,5,7]| |滤膜相互作用|电荷|药物带负电荷较带正电荷易易被滤膜吸附清除[8]| |亲脂性/亲水性|Vd|亲脂性药物,Vd一般≥2L/kg,清除有限,通常无需调整剂量[5];亲水性药物,Vd通常较小,易被CRRT清除,常需调整剂量[9,10]| |清除途径|经肾清除|肾清除药物受CRRT影响显著,需进行剂量调整;非肾清除(或肾脏清除<25%~30%)药物受CRRT影响较小,一般无需调整[3,5,11]|

注: CRRT:连续性替代治疗;Vd:分布容积 CRRT:continuous,renal replacement therapy;Vd:volume of distribution

Table 4 Changes in PK characteristics during CRRT

|变化点|原因|影响| |---|---|---| |Vd 增大|高血压和高血容量状态|增加血管通路压力,影响超| |蛋白结合率降低|血管活性药物|滤效率及药物清除[9-10]| |蛋白结合率降低|感染消耗|增加高蛋白结合率药物的游离浓度(如头孢曲松)[13]| |蛋白结合率降低|毛细血管渗漏|松)[13]| |蛋白结合率降低|酸碱失衡|药物CL变化| |蛋白结合率降低|尿毒症毒素|| |$T_{1/2}$ 改变[11,14-15]|CRRT模式及参数|药物CL变化| |$T_{1/2}$ 改变[11,14-15]|残余肾功能状态|| |$T_{1/2}$ 改变[11,14-15]|体外膜肺氧合||

注: CRRT:连续性肾替代治疗;PK:约代动力学;Vd:分布容积;$T_{1/2}$:消除半衰期;CL:清除率 CRRT:continuous renal replacement therapy;PK:pharmacokinetics;Vd:volume of distribution;$T_{1/2}$:elimination half-life;CL:clearance

3. CRRT特殊情况下抗菌药物调整策略

3.1 有残余肾功能(residual renal function, RRF)患儿行 CRRT 期间.治疗方案应如何制定与调整?

推荐意见1:对于接受CRRT治疗且存在RRF的儿童患者,药物清除能力较24h无尿状态显著增加,同时应关注患儿从无尿到肾功能恢复过程中药物清除能力的变化,动态调整治疗方案。建议综合患儿RRF水平、CRRT参数及药物PK/PD特征调整治疗方案,推荐条件允许时实施TDM以指导个体化给药(强推荐:9.33分)。

推荐依据:RRF指自然肾脏在接受替代治疗期间所保留的功能[16]。当估算肾小球滤过率(estimated glomerular filtration rate, eGFR)≥10 mL/(min·1.73m$^{2}$)或

尿量≥0.5 mL/(kg·h)时,需重视 RRF 的临床影响[17-18]。目前,测量 RRF 的最佳方法尚未确立。在启动 CRRT 前,肾小球滤过率(glomerular filtration rate, GFR)常通过基于血肌酐水平的公式估算:儿童患者多采用 Schwartz 公式[19],也可参考改良的 Q-based 方程[20];开始 CRRT 后,GFR 需基于 24 h 尿中肌酐和尿素 CL 的平均值评估[8](表5)。

在 CRRT 期间,药物的清除由3部分构成,即 CRRT 清除、RRF 清除以及非肾清除途径,其关系可表示为[18]:$CL_{总}=CL_{CRRT}+CL_{残余肾}+CL_{非肾}$。主要经肾排泄的药物受 RRF 影响尤为突出[21],可在估算出 $CL_{CRRT}$ 后,将 $CL_{残余肾}$ 及 $CL_{非肾}$ 纳入考量,维持剂量参考肾功能水平相当患者的推荐方案[8],并尽可能开展 $TDM^{[15]}$。主要经非肾途径清除的药物通常无需调整剂量[8]。

Table 5 Commonly used GFR estimation formulas

|名称|公式| |---|---| |Schwartz 公式(2009更新版)[22]|eGFR=0.413×身高(cm)/血肌酐(mg/dL)| |Q-based 方程[20]|eGFR=M/[血肌酐(µmol/L)/Q]| |基于肌酐和尿素CL的平均值评估[8,23]|2岁以下M值=100.2;2岁及2岁以上M值=107.3Q值:男童为19.5+3.2×年龄;女童为23.6+2.2×年龄eGFR(mL/min)=[尿肌酐(mg/dL)]/血肌酐(mg/dL)+尿液尿素氮(mg/dL)/血尿素氮(mg/dL)]×尿量(mL/d)/(2×1440)| ||体表面积校正:eGFR[mL/(min·1.73m²)]=eGFR(mL/min)×1.73/体表面积(m²)|

注:GFR:肾小球滤过率;eGFR:估算肾小球滤过率;CL:清除率;1 $mg/dL \approx 88.4 \ \mu mol/L$ GFR:glomerular filtration rate;eGFR:estimated glomerular filtration rate;CL:clearance;1 $mg/dL \approx 88.4 \ \mu mol/L$

3.2新生儿与早产儿行 CRRT期间如何制定治疗方案?

推荐意见2:新生儿与早产儿行CRRT期间,暂无剂量推荐,需结合患儿的发育差异及药物PK特点,基于现有循证证据与临床经验制定个体化治疗方案。推荐开展TDM,结合疗效与安全性动态调整治疗方案,确保PK/PD达标,实现个体化精准治疗(强推荐:8.95分)。

推荐依据:目前缺乏该群体 CRRT 治疗时的 PK 数据,现有证据主要来源于少量病例报告及涵盖广泛年龄范围(0.03~18.00岁)的研究,结果显示个体间差异较大[24-27]。由于肝肾功能个体发育差异显著且动态变化[28],加之 CRRT 时体外循环血量占比较高,对药物 Vd 影响更大,进一步加剧个体间 PK 差异。因此,基于 PopPK 模型的标准化治疗方案在此类患者中适用性有限。建议结合现有证据和经验制定治疗方案,并基于病原菌最低抑菌浓度(minimum inhibitory concentration, MIC)和 TDM 结果进行个体化调整,以优化疗效并预防毒性。

3.3 儿童行 CRRT期间联用多种药物时，如何管理以降低药物相互作用相关风险？

推荐意见3:儿童行CRRT期间，若联合使用可能存

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 注: CRRT:连续性肾替代治疗;Vd:分布容积;RRF:残余肾功能;CL:清除率;PK:药代动力学;PD:药效动力学;TDM:治疗药物监测;PopPK:群体药代动力学 CRRT:continuous renal replacement therapy;Vd:volume of distribution;RRF:residual renal function;CL:clearance;PK:pharmacokinetics;PD:pharmacodynamics;TDM:therapeutic drug monitoring;PopPK:population pharmacokinetics

图1 CRRT期间治疗方案调整流程图

Figure 1 Flowchart for treatment regimen adjustment during CRRT

在相互作用的药物,推荐开展 TDM。同时,推荐在条件允许时由包含临床药师在内的跨学科协作团队实施联合查房并指导用药(强推荐:9.38分)。

推荐依据:接受 CRRT 的患儿常需联合使用多种药物(如抗菌药物、抗凝药物、心血管活性药物及免疫抑制剂),药物间相互作用可能影响非肾途径的清除,进而改变总体$CL^{[15,21]}$。例如伏立康唑与质子泵抑制剂(如奥美拉唑)、抗血小板药物(如氯吡格雷)、免疫抑制剂(如他克莫司)等联用时,可能因 PK 参数改变引起剂量不足或过量风险[28-31]。因此,推荐通过 TDM 指导此类药物的治疗方案调整。临床药师可在预测相互作用、加强监测及制定个体化方案方面发挥关键作用,以降低相关风险[31-32]。

4 CRRT期间儿童常用抗菌药物调整方案

本共识将常用抗菌药物划分为“无需调整剂量”与

“需要调整剂量”两大类(表6)。本部分推荐意见基于专家共识及有限的循证医学证据,主要适用于因少尿或无尿接受 CRRT 治疗的危重症患儿。针对这些患儿建议优先使用主要经非肾途径代谢或肾毒性小的药物。如果因病情需要必须使用肾毒性较大的药物,请按照要求进行 TDM。对于当前证据尚不充分、无法形成推荐意见的药物,本共识暂未纳入。

4.1 抗细菌药物

4.1.1 哌拉西林/他唑巴坦

推荐意见4:CVVHDF期间给药建议(以哌拉西林计):(1)连续输注(首选方案):200 mg/(kg·d),连续输注24 h;(2)间歇输注(替代方案):100 mg/(kg·次),q8h,输注30 min(强推荐:8.77分)。

推荐依据:基于一项儿童PopPK研究,在CVVHDF模式下,哌拉西林200 mg/kg,24 h持续输注可使90%以上患儿达到100%fT>$1 \times MIC$。替代方案为100 mg/kg,

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表6 抗菌药物分类推荐汇总表

Table 6 Summary table of recommended classification of antimicrobial agents.

|分类|抗细菌药物|抗真菌药物| |---|---|---| |无需调整剂量|苯唑西林、头孢克洛、头孢曲松、头孢哌酮/舒巴坦$^{a}$、氨曲南、莫西沙星$^{a}$、红霉素、阿奇霉素、克林霉素、利奈唑胺、替加环素、硫酸多黏菌素B、硫酸黏菌素、米诺环素、多西环素|伏立康唑、伊曲康唑、泊沙康唑、艾沙康唑、米卡芬净$^{a}$、卡泊芬净$^{a}$、两性霉素B(脱氧胆酸盐$^{a}$,胆固醇硫酸酯复合物$^{a}$以及脂质体)| |需要调整剂量|氨苄西林、哌拉西林、头孢唑林、头孢西丁$^{a}$、头孢呋辛、头孢洛生/他唑巴坦、头孢吡肟、头孢噻肟、阿莫西林/克拉维酸、哌拉西林/他唑巴坦、头孢他啶/阿维巴坦、亚胺培南/西司他丁、美罗培南/厄他培南$^{a}$、庆大霉素、妥布霉素、阿米卡星、链霉素、环丙沙星、左氧氟沙星、多黏菌素E甲磺酸钠$^{a}$、万古霉素、替考拉宁$^{a}$、去甲万古霉素$^{a}$、达托霉素$^{a}$、复方磺胺甲噁唑|氟康唑|

注:TDM:治疗药物监测;CRRT:连续性肾替代治疗;将常用抗菌药物分为“无需调整剂量”与“需要调整剂量”两大类,仅基于现有数据,推荐并非绝对。临床仍需结合患儿具体病情综合判断;表示儿童CRRT数据极度缺乏,推荐方案主要基于成人数据外推或理论计算,临床应用时不确定性高,使用时建议尽一切可能开展TDM TDM:therapeutic drug monitoring;CRRT:continuous renal replacement therapy;common antimicrobial agents are categorized into 2 groups: "no dosage adjustment required" and "dosage adjustment required". These recommendations are based solely on available data and are not absolute. Clinical decisions must be tailored to the specific condition of each pediatric patient; "pediatric data on CRRT are extremely scarce. The recommended regimens are primarily extrapolated from adult data or derived from theoretical calculations,entailing a high degree of uncertainty in clinical application. TDM is strongly advised whenever feasible

q8h, 输注30 min[33]。另外,当CVVH或CVVHD超滤液流速和透析液流速之和<1 500 mL/(m$^{2}$·h)时,建议哌拉西林剂量为70 mg/kg, q6~8h;当流速之和≥1 500 mL/(m$^{2}$·h)时,可调整为70~100 mg/kg, q6~8h[18]。

4.1.2 头孢吡肟

推荐意见5:CRRT期间建议给予50 mg/(kg·次), q8~12h,单次最大剂量为2 g。对于$CL_{CRRT}$高,MIC较高菌株或危重症患儿的严重感染,可考虑延长输注时间或增加给药频次(强推荐:8.90分)。

推荐依据:国外《肾功能衰竭患者的药物处方——成人及儿童用药剂量指南》[32]建议,儿童CRRT时头孢吡肟治疗方案为50 mg/kg, q12h。当 CVVH 或 CVVHD 超滤液流速和透析液流速之和<1 500 mL/($m^2 \cdot h$)时,调整为 25 ~ 50 mg/kg, q12 ~ 18h;当流速之和≥1 500 mL/($m^2 \cdot h$)时,调整为 25 ~ 50 mg/kg, q12h[18]。一项回顾性研究(n=4, CVVHDF 模式)显示,危重患儿使用50 mg/kg, q12h 可能难以达到100%fT>4×MIC的PK/PD目标,并强烈建议进行TDM[34]。另一项研究(n=3)表明,50 mg/kg, q8~12h或1g, q8h可使所有患儿达到100%fT>1×MIC[35]。

4.1.3 头孢他啶/阿维巴坦(Ceftazidime/Avibactam, CAZ/AVI)

推荐意见6:在CVVHDF模式下,CAZ和AVI均可被清除,对于危重症患儿和高 MIC菌株感染患儿,可根据不同年龄段给予常规剂量,通过延长输注时间(如3~4h)达到PK/PD目标(强推荐:8.59分)。

推荐依据:目前儿童数据极为有限。成人病例(n=1, CVVHDF)显示 CAZ/AVI 2.5 g, q8h 可达 PK/PD 靶值(CAZ:100%fT>4×MIC; AVI:50%fT>1 mg/L)。对于MIC<4 mg/L,血流感染或尿路感染时,也可考虑1.25 g, q8h[36]。另一项成人研究[n=8, CVVHDF=38.6 mL/ (kg·h)]显示,1.25~2.50 g, q8h,持续输注,CAZ 可达

稳态血药浓度(steady-state concentrations, $C_{ss}$)/MIC $\ge 4^{[37]}$。一项儿童病例报告(n=1, CVVHDF)显示 CAZ/AVI 30 mg/7.5 mg/kg, q8h, 持续输注2h并未达到PK/PD目标[38]。结合该患儿体内外模拟试验结果, CAZ和AVI在CRRT条件下CL较高, 可能需要更高的剂量(如以CAZ计, 40~50 mg/kg, q8h)或延长输注(如3~4h)/持续输注以达到治疗水平。同时, 推荐依据TDM结果调整[39]。

4.1.4美罗培南

推荐意见7:CRRT期间常规推荐20 mg/(kg·次), q8h, 输注1~4 h; 在某些情况下(严重感染或 MIC ≥ 4 mg/L), 建议提高至40 mg/(kg·次), q8h, 输注时间≥3 h; 单次最大剂量不超过2 g(强推荐:9.15分)。

推荐依据:(1)对于MIC=4 mg/L的病原菌(n=9, CVVH/CVVHDF模式):40 mg/kg,q12h,输注30 min,仅32%的患儿达到100%fT>MIC;而20 mg/kg,q8h(4 h输注)或40 mg/kg,q8h(输注≥2 h),可使90%以上的患儿达到100%fT>MIC[40]。(2)对于MIC>4 mg/L的病原菌(n=11):60 mg/(kg·d)和120 mg/(kg·d)连续输注可达到PK/PD靶值(50%fT>MIC和100%fT>MIC)[41]。(3)对于MIC<4 mg/L的病原菌:①重症监护病房患儿(n=31,CVVHD或CVVHDF模式):20~40 mg/kg,q8h,输注30 min或3 h;或60~120 mg/(kg·d)持续输注,均可实现40%fT>MIC[42];②脓毒症患儿(n=9,CVVHDF模式):40 mg/kg,q8h,3 h输注方案,100%fT>MIC的达标率为77.4%;40 mg/kg,q8h,1 h输注,可达到50%fT>MIC[43];③120 mg/(kg·d),连续输注,所有患儿可实现100%fT>MIC[42]。

4.1.5亚胺培南/西司他丁

推荐意见8:CRRT期间治疗方案调整为7~13 mg/（kg·次）（以亚胺培南计），q8h(强推荐:8.69分)。

推荐依据:目前缺乏亚胺培南/西司他丁在儿童CRRT中PK的研究。国外《肾功能衰竭患者的药物处

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方——成人及儿童用药剂量指南[32]建议,CRRT时,亚胺培南/西司他丁调整为7~13 mg/(kg·次),q8h(以亚胺培南计)。

4.1.6复方磺胺甲恶唑

推荐意见9:CRRT会增加磺胺甲恶唑(Sulfamethoxazole, SMZ)的清除,而对甲氧苄啶(Trimethoprim, TMP)清除影响较小。CRRT期间可考虑先给予常规剂量,根据TDM结果动态调整治疗方案(强推荐:8.49分)。

推荐依据:成人病例报告显示($n=2$, CVVHDF模式),给予常规剂量的50%,TMP的CL(21.5~28.9 mL/min)接近正常肾脏的CL(20~80 mL/min),而SMZ的CL(18.7~42.6 mL/min)变异度较大,远超正常值(1~5 mL/min)[44]。一项基于成人的研究同样显示($n=168$,未明确 CRRT模式),CRRT时SMZ的CL显著增加,而对TMP的CL影响较小,CRRT患者SMZ剂量需加倍以达到相同的暴露水平[45]。当CVVH或CVVHD超滤液流速和透析液流速之和<1 500 mL/($m^2 \cdot h$)时,可考虑TMP 3~5 mg/kg,q18h;当流速之和≥1 500 mL/($m^2 \cdot h$)时,可考虑TMP 4~5 mg/kg,q18h[18]。对于儿童耶氏肺孢子菌感染,建议TMP 5 mg/kg,q8h[18]。

4.1.7阿米卡星

推荐意见10:CRRT期间推荐治疗方案为7.5 mg/（kg·次），q12h(强推荐:8.64分)。

推荐依据:系统评价显示,CVVH<1~2 L/h,GFR<15~30 mL/min时,推荐剂量为10 mg/kg,q24h[21]。另一项系统评价显示,CVVH和CVVHD模式下,首次给药剂量建议为5.0~7.5 mg/kg[18]。国外《肾功能衰竭患者的药物处方——成人及儿童用药剂量指南》[32]建议CRRT时调整为7.5 mg/kg,q12h。

4.1.8 环丙沙星和左氧氟沙星

推荐意见11:CRRT期间,环丙沙星推荐治疗方案为10~15 mg/(kg·次),q12h;左氧氟沙星推荐治疗方案为10 mg/(kg·次),q24h(强推荐:8.62分)。

推荐依据:系统评价显示,环丙沙星儿童常规推荐剂量为10 mg/kg,q12h,当CVVH<1~2 L/h,GFR<15~30 mL/min时,建议剂量减少25%,q12h[21]。另外,国外《肾功能衰竭患者的药物处方——成人及儿童用药剂量指南》[32]建议使用10~15 mg/kg,q12h,推荐通过TDM进行剂量调整。

相比环丙沙星,左氧氟沙星在 CVVH 和 CVVHDF 期间 CL 显著增加。系统评价显示,当 CVVH<1~2 L/h, GFR<15~30 mL/min 时,推荐剂量为 5~10 mg/kg, q24h,无需剂量调整[21]。对于≤10岁的儿童,CRRT 期间建议调整为 10 mg/kg, q24h[32]。

4.1.9 万古霉素

推荐意见12:万古霉素在CRRT期间PK变异极

大,建议初始治疗方案为15~20 mg/(kg·次),q8~12h,须在首次给药后24~48 h内启动TDM,并基于血药浓度-时间曲线下面积(area under the curve,AUC)/MIC或谷浓度(minimum plasma concentration,$C_{min}$)进行个体化调整。不推荐在未进行TDM的情况下长期使用固定治疗方案(强推荐:9.18分)。

推荐依据:国外《肾功能衰竭患者的药物处方——成人及儿童用药剂量指南》[32]建议 CRRT 时调整为10 mg/kg, q12h。一项儿童回顾性研究(n=41,86%的患儿有残余尿量)显示,接受 CRRT 通常需要 17.5 mg/kg, q12h 的治疗方案[46]。另一项研究表明,为达到 AUC/MIC>400 mg·h/L 且 $C_{min}<20$ mg/L, CVVHDF 患儿可基于去脂体重给予 40~50 mg/(kg·d), q8~12h, 并需严格监测血药浓度[47]。一项前瞻性研究结果显示:(1)接受体外膜肺氧合(extracorporeal membrane oxygenation, ECMO)且无 AKI/CRRT 的患儿(n=15),与无 ECMO 的重症患儿相比,Vd相似但CL较低,建议初始剂量为40 mg/(kg·d), q6h,并在治疗24 h后根据血药浓度水平调整剂量;(2)接受 ECMO 并伴有 AKI/CRRT 的患儿(n=11),需要使用较低的剂量[20 mg/(kg·d), q12h],并根据肾功能进行调整;(3)ECMO+CRRT 但未发生 AKI 的患儿(n=3),推荐剂量为40 mg/(kg·d), q6h;该研究强烈建议对所有接受 ECMO 的患儿开展 TDM 指导万古霉素用药[48]。

4.1.10 利奈唑胺

推荐意见13:CRRT期间通常无需调整剂量(强推荐:8.95分)。

推荐依据:利奈唑胺主要经非肾途径清除,国外《肾功能衰竭患者的药物处方——成人及儿童用药剂量指南》[32]建议 CRRT 期间无需调整剂量。一项儿童PopPK研究(n=15)显示,CRRT 对利奈唑胺关键 PK 参数未产生显著影响[49]。

4.1.11 硫酸多黏菌素B、多黏菌素E甲磺酸钠和硫酸黏菌素

推荐意见14:(1)硫酸多黏菌素B主要经非肾途径清除,接受CVVHDF的患儿原则上无需调整剂量。(2)多黏菌素E甲磺酸钠缺少儿童研究数据,参照成人数据建议首剂给予负荷剂量,24 h后给予维持剂量。(3)硫酸黏菌素虽然主要经肾途径清除,但CRRT对硫酸黏菌素的清除影响较小,无需调整剂量。停用CRRT后,需根据肾功能和药物暴露重新评估(强推荐:8.51分)。

推荐依据:硫酸多黏菌素B经血管内给药后可直接发挥抗菌活性,主要经非肾脏途径代谢;多黏菌素E甲磺酸钠为前体药物,需要转化为多黏菌素E后才能发挥抗菌作用,大部分以原型经肾脏排泄;硫酸黏菌素仅在国内上市,暂缺乏儿童PK研究。

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成人行 CRRT 时无需调整硫酸多黏菌素B的剂量[5],而国内儿童病例报告(n=2, CVVHDF 模式)显示 CRRT 显著降低药物暴露,CRRT 期间的稳态平均血药浓度(average steady-state plasma concentration, $C_{ss,avg}$)仅为非 CRRT 期间的53%~58%[50]。2 例患儿接受1 mg/kg, q12h 初始剂量时, $C_{ss,avg}$ 均未能达标;当剂量增至2 mg/kg, q12h 后, $C_{ss,avg}$ 分别达到2.60 mg/L 和1.73 mg/L,感染得到有效控制[50]。

目前暂无儿童 CRRT 治疗期间多黏菌素E甲磺酸钠剂量调整相关数据,成人研究提示 CRRT可以有效清除多黏菌素E甲磺酸钠和多黏菌素E活性基质,首剂给予负荷剂量,24 h后给予维持剂量,有助于更快达到目标浓度$^{[5]}$。

儿童研究显示 CRRT 组与非 CRRT 组相比,硫酸黏菌素 $C_{min}$、峰浓度(maximum plasma concentration, $C_{max}$)以及临床疗效差异无统计学意义,提示 CRRT 对硫酸黏菌素的消除影响较小,但从安全性角度考虑,建议对接受 CRRT 的患儿常规进行 TDM[51]。另1例ECMO联合CRRT 治疗的患儿,治疗前后硫酸黏菌素 $C_{min}$ 和 $C_{max}$ 无显著差异,提示接受 ECMO 联合 CRRT 治疗患儿无需调整剂量[52]。

4.2 抗菌药物

4.2.1 氟康唑

推荐意见15:在CVVHD治疗期间,氟康唑的CL增加,建议2倍维持剂量作为负荷剂量;维持剂量为6~12 mg/(kg·次),q24h,单次最大剂量为800 mg(强推荐:8.56分)。

推荐依据:国外《肾功能衰竭患者的药物处方-成人及儿童用药剂量指南》[32]建议 CRRT 期间剂量为6 mg/kg, q24h; 系统评价显示, 静脉或口服负荷剂量6~10 mg/kg(或以2倍维持剂量作为负荷剂量), 当 CVVH 或 CVVHD 超滤液流速和透析液流速之和<1 500 mL/($m^2 \cdot h$)时, 维持剂量3~12 mg/kg, q24h; 当流速之和≥1 500 mL/($m^2 \cdot h$)时, 维持剂量6~12 mg/kg, q24h[18]。

病例报告显示($n=1, CVVHD$模式),需要静脉给予首剂负荷剂量900 mg,维持剂量600 mg(即10 mg/kg), q12h才能达到PK/PD目标[53]。另一项针对婴儿的PK研究显示,对于预防器官移植相关真菌感染(同时接受CRRT和ECMO),25 mg/kg,静脉注射,1次/周,足以达到PK/PD目标(血药浓度高于MIC)[54]。

4.2.2 伏立康唑、泊沙康唑、艾沙康唑、卡泊芬净、米卡芬净、两性霉素B

推荐意见16:CRRT对伏立康唑、泊沙康唑、艾沙康唑、卡泊芬净、米卡芬净、两性霉素B(脱氧胆酸盐,胆固醇硫酸酯复合物以及脂质体)等药物体内清除影响较

小,CRRT期间无需调整治疗方案(强推荐:8.90分)。

推荐依据:研究报道1例接受CVVH和静脉-静脉ECMO联合治疗的患儿(5岁),推荐伏立康唑治疗曲霉菌感染剂量为10~14 mg/kg,q12h[55]。目前关于泊沙康唑和艾沙康唑,儿童CRRT治疗期间暂无剂量推荐,基于其主要经非肾途径清除,推测在CRRT期间原则上不需要调整剂量。

一项成年肝移植患者研究表明(n=6, CVVH 模式),米卡芬净40~50 mg/d可以达到治疗目标,CVVH对其 PK 影响较小,无需调整剂量[56]。此外,研究发现卡泊芬净在离体 CVVHDF 模式回路中,电路CL极低(0.40 mL/min)并且不受$CL_{CRRT}$影响[57]。国外《肾功能衰竭患者的药物处方——成人及儿童用药剂量指南》[32]建议米卡芬净和卡泊芬净在CRRT期间无需调整剂量。

两性霉素B脂质体具有高亲脂性、高蛋白结合率,在肾组织浓度低,呈非线性PK特征。研究表明,两性霉素B脂质体在CVVH模式下体外CL低,CRRT期间无需调整剂量[21,57]。目前缺乏两性霉素B脱氧胆酸盐、两性霉素B胆固醇硫酸酯复合物在儿童CRRT期间的剂量研究,基于PK特征推测无需调整剂量。

5 CRRT期间TDM开展建议

推荐意见17:对于肾毒性较大的药物(如万古霉素、多黏菌素类、阿米卡星、复方磺胺甲恶唑等)及个体化差异较大或治疗窗较窄的药物(如伏立康唑),推荐常规开展TDM指导个体化用药。对于其余药物,受限于循证证据、检测条件及获益-风险平衡,鼓励有条件的医疗机构开展TDM(附录B)(强推荐:8.20分)。

推荐依据:万古霉素主要经肾清除,CRRT会影响其暴露水平,常规治疗方案往往难以达到治疗目标[58-59]。研究表明TDM在保障万古霉素的疗效和安全性方面发挥重要作用[47-48,60]。关于多黏菌素类药物,基于其肾毒性及CRRT对其代谢影响差异,从疗效和安全性角度考虑,建议对接受CRRT的患儿常规进行TDM[61-66]。氨基糖苷类药物是小分子亲水性物质,主要经肾脏排泄。相较于肾功能正常者,接受CRRT治疗的危重症患者,其阿米卡星与妥布霉素的CL降低,Vd增大。同时研究表明在CVVH与CVVHD两种模式下,上述药物的Vd亦存在显著差异[67]。另有阿米卡星PopPK研究证实,大剂量给药(25 mg/kg,q48h)联合延长给药间隔,并配合TDM是CRRT危重症患者应用该类药物的优选方案[68]。此外,研究表明CRRT时TMP跨膜CL高于SMZ[69];另有研究显示,CRRT时常规则量的TMP/SMZ治疗与嗜麦芽窄食单胞菌感染导致的高失败率以及死亡率相关[70]。因此,结合该药安全性特点,有必要开展

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TDM 指导用药。伏立康唑主要通过肝脏代谢,研究表明 CVVH 对其清除作用较小,标准静脉剂量可有效达到大多数病原体的目标血浆浓度[71]。然而其治疗窗较窄,$C_{min}$过低(<1 mg/L)时治疗效果较差,过高(>5.5 mg/L)则与视力障碍、神经毒性和肝毒性的发生率增加有关,且伏立康唑在儿童中血药浓度差异显著大于成人,因此TDM是确保其有效暴露同时避免毒性的必要手段[72-76]。

综上所述,CRRT显著影响抗菌药物的PK特点,结合危重患儿的个体差异,规范TDM是优化治疗的关键。本共识基于循证医学证据和临床实践经验,针对万古霉素等抗细菌药物及伏立康唑等抗真菌药物,制定了包含监测指标、监测时机、目标浓度、重复监测时机以及治疗方案调整策略等要点的TDM策略。然而,TDM工作需要注意以下几点:(1)目标浓度多引自群体数据,需考虑个体差异;(2)$CL_{CRRT}$受滤器参数、药物理化特性等多种因素影响;(3)部分药物儿童数据有限,多参照成人的研究数据。因此,TDM结果仅作为临床决策的重要参考依

据,而非唯一标准,必须结合患儿的治疗反应情况进行个体化评估。

6小结与展望

本共识系统梳理了儿童 CRRT 期间抗菌药物治疗方案调整的关键问题,共提出17条推荐意见,涵盖CRRT期间影响抗菌药物方案的主要因素、特殊情况下的治疗方案调整、常用抗菌药物具体调整方案及TDM策略,强调了跨学科协作的重要性。然而,本共识仍存在一定局限性。(1)患儿招募困难、伦理与技术壁垒高以及成本高昂导致儿童 CRRT 期间抗菌药物高质量研究缺乏;(2)部分推荐基于病例报告或成人数据外推,循证依据有限。未来应秉持“有证用证,无证创证”的原则,推动以下研究:(1)开展儿童 CRRT 时 PopPK 研究,尤其针对新生儿、早产儿及不同 CRRT 模式下的药物清除规律;(2)开发基于人工智能的剂量预测模型,实现动态个体化给药;(3)加强 TDM 在基层医疗机构的普及,建立多中心儿童 CRRT 药物浓度监测网络。

(文庆段淑倪梁倩莹李天姿杨梅执笔)

附录A 儿童患者 PK 参数

|抗菌药物|相对分子质量|蛋白结合率(%)|半衰期(h)|儿童患者|儿童患者|重症儿童患者|重症儿童患者|主要清除方式|PK/PD特征|参考文献| |---|---|---|---|---|---|---|---|---|---|---| |抗菌药物|相对分子质量|蛋白结合率(%)|半衰期(h)|Vd(L/kg)|CL[L/(kg·h)]|Vd(L/kg)|CL[L/(kg·h)]|主要清除方式|PK/PD特征|参考文献| |哌拉西林|517|16|1|0.57~10.00|0.108~0.860|$0.780^{a}$|$0.097^{a}$|经肾清除|时间依赖性|[77-81]| |他唑巴坦|300|48|1|0.11~0.13|0.13|-|-|经肾清除|时间依赖性|[77]| |头孢哌酮|668|70.0~93.5|1.7|0.058~0.089|0.084~0.110|0.22|0.14|经胆道清除|时间依赖性|[82-83]| |舒巴坦|255|38|1|0.395|0.359|0.686|0.970|经肾清除|时间依赖性|[83-84]| |头孢他啶|636|17|2.8|0.10~0.24|0.34~0.46|0.087|0.200|经肾清除|时间依赖性|[85-88]| |阿维巴坦|265|5.7~8.2|2.7|0.20~0.68|0.67~0.36|$0.15^{a}$|$0.36^{a}$|经肾清除|时间依赖性|[38,89]| |美罗培南|438|2|1|0.13~0.47|0.18~0.64|0.05~2.04|0.04~0.63|经肾清除|时间依赖性|[25,40-43,90-92]| |||||||$0.13~0.19^{a}$|$0.04~0.16^{a}$|||| |亚胺培南|240|15~25|1|0.73~0.78|0.26~0.95|0.20~0.76|0.23~0.48|经肾清除|时间依赖性|[93-95]| |复方磺胺甲哌唑|290|SMZ 70;TMP 44|SMZ 9/TMP 11|SMZ 0.086~0.410;TMP 1.840~2.470|SMZ 0.021~0.026;TMP 0.130~0.160|-|-|经肾清除|尚不清楚|[96]| |阿米卡星|585|0~10|2~3|0.24~0.57|0.026~0.140|-|-|经肾清除|浓度依赖性|[97-98]| |环丙沙星|331|20~40|4|0.06~3.04|0.16~1.12|-|-|经肾清除|浓度依赖性|[99-100]| |左氧氟沙星|361|24~38|7|0.74~1.49|0.13~0.48|-|-|经肾清除|浓度依赖性|[101]| |替加环素|585|71~89|42|0.04~9.72|0.21~0.80|-|-|经肾及胆道清除|时间-浓度依赖性|[102-103]| |万古霉素|1448|10~55|4~6|0.60~1.60|0.02~0.11|0.68~1.60|0.38~1.67|经肾清除|时间-浓度依赖|[24,47,48,104-109]| |||||||$0.26~1.05^{a}$|$0.02~0.11^{a}$|||| |利奈唑胺|337|31|5|0.07~1.24|0.03~0.56|-|0.030~0.039|非肾清除|时间依赖性|[49,110-113]| |多黏菌素B|1189|60|2.70~5.52|0.123~0.185|0.042~0.076|-|-|非肾清除|浓度依赖性|[114]| |多黏菌素E甲磺酸钠|1748|&gt;50|4.96|0.660|0.069|1.38|0.27|经肾清除|浓度依赖性|[115-116]| |氟康唑|306|10|20~50|0.70~5.71|0.005~0.046|$0.55~1.37^{a}$|$0.080~0.042^{a}$|经肾清除|浓度依赖性|[54,117-119]| |伏立康唑|349|58|6|4.6|0.20~0.58|0.38~0.89|-|代谢物经尿清除|时间-浓度依赖性|[120-121]| |泊沙康唑|700|98~99|20~66|1.09~4.67|0.06~0.12|-|-|经粪便清除|时间-浓度依赖性|[122-124]| |艾沙康唑|437|99|130|6.4|0.004 3~0.046 0|-|-|代谢物经尿及粪便清除|时间-浓度依赖性|[125]| |卡泊苏净|1213|97|13|$ 1.72\,\text{L/m}^2 $|$ 0.15\sim 0.47\,\text{L/(h·m}^2\text{)} $|-|-|代谢物经尿及粪便清除|浓度依赖性|[126-127]| |米卡芬净|1292|99|15~17|0.12~0.66|0.009 9~0.069 0|$0.075~0.091^{a}$|$0.004 8~0.005 3^{a}$|经粪便清除|浓度依赖性|[56,128-130]| |两性霉素B脂质体|924|91~95|6.8|0.16~2.59|0.007~0.098|-|-|缓慢经肾清除|浓度依赖性|[131-132]| |两性霉素B脱氧胆酸盐|924|91~95|5~82|0.1~17.5|$ 0.8\sim 7.5\,\text{L/(h·m}^2\text{)} $|-|-|经肾及胆道清除|浓度依赖性|[133-134]|

注:PK:药代动力学;Vd:分布容积;CL:清除率;PD:药效动力学;SMZ:磺胺甲噁唑;TMP:甲氧苄啶;CRRT:连续性肾替代治疗;a为CRRT模式下的数据

中华实用儿科临床杂志2026年4月第41卷第4期 Chin J Appl Clin Pediatr, April 2026, Vol. 41, No. 4

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附录B 抗菌药物 TDM 监测要点汇总表

|药物|监测指标|监测时机*|目标浓度b|重复监测时机c|治疗方案调整策略| |---|---|---|---|---|---| |哌拉西林/他唑巴坦|Cmax或fc135-136||哌拉西林;|①Cc.4-8xMC[135]|①Cc.10xMC,剂量减少50%;Cmax~20%| |哌拉西林/他唑巴坦|Cmax或fc135-136||②目标治疗;FCmax-4xMIC,Cmax&lt;160 mg/L;经验治疗;Cmax为80~160 mg/L;136]|同哌拉西林/他唑巴坦[135]|同哌拉西林/他唑巴坦[135]| |头孢哌肟|Cmax[135]||Cmax4-8xMC[135]|同哌拉西林/他唑巴坦[135]|同哌拉西林/他唑巴坦[135]| |头孢他啶/阿维巴坦|Cmax[135]||①头孢他啶,Cmax-4xMIC[135]②头孢他啶,50%f/T&gt;MIC,阿维巴坦;50%f/T&gt;1 mg/L;157-136]|同哌拉西林/他唑巴坦[135]|| |美罗培南|①Cminos或fc135,139②特殊情况可联合监测|Cminos或fc4-5剂后下给药前30 min 内监测(危患者建议于给药1~2剂后监测)[141-142]|①Cminos&lt;32 mg/L(降低不良反应的发生[141,143])②一般感染;9/T MIC ≥40%&lt;50%;重症感染;9/T MIC ≥100%,即Cminos≥MIC,甚至Cminos≥4x MIC 时疗效较好[141]|①患者肾功能显著变化(如AKI或恢复期)[144]②临床疗效不佳或感染复发[139]|| |亚胺培南d|fcmin或fcmin||③Cminos-4-8xMC[135]③目标治疗;FCmin≥4xMIC,Cminos&lt;5 mg/L;经验治疗;FCmin为2.5-5.0 mg/L[136]|①患者的疾病状态发生变化②给药途径改变③调整治疗方案48h后采血|基于TDM结果个体化调整| |复方磺胺甲唑唑*|Cminos或fcmin||一般病原体TMP 1.5-2.5 mg/L; SMS 30-60 mg/L;耶氏肺孢子菌 TMP 5-10 mg/L; SMZ 100~200 mg/L;诺卡菌 SMZ 100~150 mg/L[146]|①患者的疾病状态发生变化②给药途径改变③调整治疗方案48h后采血|基于TDM结果个体化调整| |阿米卡星*|Cminos或fcmin和AUC0-24h[147-148]||①Cminos应&lt;35 mg/L[149]②轻度中度感染;AUC0-24h;MIC为30-50[148];危重成人患者建议AUC0-24h/MIC为80-100,Cmax&gt;MIC≥8~10,Cminos&lt;2.5 mg/L[150];振毒症患者建议Cmax&lt;2/MIC 8~12;Cminos&lt;5 mg/L[147]①|①Cminos~MC&lt;8,日剂量增加25%~30%,最多达到30 mg/kg②minos~MC&lt;12,减少25%~30%,最小值为7.5 mg/kg③minos&gt;5 mg/L,给药间隔延长至12 h(最多72 h)[147]|| |环丙沙星|Cminos或fcmin和AUC0-24h[135,150]||①Cminos~MC,Cminos&lt;2 mg/L[135]②危重成人患者建议喹诺酮类/AUC0-24h/MIC≥80,Cminos&gt;8~12[150]|①Cminos&gt;2 mg/L,剂量每36~48 h下调②minos&lt;10xMIC,上调25%[135]|| |左氧氟沙星|Cminos或fcmin和AUC0-24h[135,150]||①Cminos&gt;10xMIC,Cminos&lt;3 mg/L[135]②危重成人患者建议喹诺酮类/AUC0-24h/MIC≥80,Cminos&gt;8~12[150]|①Cminos&gt;2 mg/L,剂量每36~48 h下调②minos&lt;10xMIC,上调25%[135]|| |万古霉素*|①Cminos或fcmin和AUC0-24h,或Cmin|①肾功能正常患者建议在给药48 h后进行首次TDM;肾功能不全患者建议在给药72 h后开展[152]②对于儿童严重MRSA感染,可在给药后24~48 h内进行[151]|①Cminos&gt;儿童/新生儿建议维持在5-15 mg/L[152,154]②AUC0-24h;400~650 mg/h/L[152,154]③cminos&gt;特殊情况下为20~40 mg/L[153]|①患者肾功能显著变化[153]②长期治疗(&gt;3-5 d)或高剂量方案(如4g/d)[155]①|①Cminos&lt;10 mg/L;按10%~20%增量[151];缩短给药间隔[156]②minos&lt;20 mg/L;按10%~20%减量;延长给药间隔③如有肾毒性(血清肌酐≥44.2 µmol/L);停药12-24 h后重新调整方案[151]| |替去拉宁|Cmin[150,157]|Cmin:在第4天尚未达到稳态时测量|①Cmin≥15-30 mg/L[150]②minos非复杂性MRSA感染为15~30 mg/L;复杂和/或严重MRSA感染为20-40 mg/L[157]|①肾功能不全患者②Cmin:需要超过20 mg/L的严重感染7 d内应进行TDM复测|基于TDM结果个体化调整| |利奈唑胺|Cminos[135,150,158]|在给药后48 h进行采样[150]|Cminos~2-8 mg/L[135,158]|①Cminos&gt;15 mg/L,剂量减少50%;Cminos~8-15 mg/L,增加25%~20minos&lt;1 mg/L,增加50%;Cminos~2-2 mg/L,增加25%[135]||

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续附录B 抗菌药物 TDM 监测要点汇总表

|药物|监测指标|监测时机$^{a}$|目标浓度$^{b}$|重复监测时机$^{ac}$|治疗方案调整策略| |---|---|---|---|---|---| |多黏菌素 $E^{c}$|$AUC_{ss,24h}$ 及 $C_{ss,avg}$ [159-160]|$C_{min}$ 和 $C_{max}$:①肾功能正常且未使用负荷剂量的患者应在第4次/第5次给药前和给药后采集②若使用了负荷剂量,则可改为在第2次/第3次给药前和给药后采集[160]|$AUC_{ss,24h}$ 为 50~100 mg/h,对应 $C_{ss,avg}$ 为 2~4 mg/L[159-160]||基于 TDM 结果个体化调整| |多黏菌素 $E^{c}$|$AUC_{ss,24h}$ 及 $C_{ss,avg}$ [159]|$AUC_{ss,24h}$ 为 50 mg/h,L,对应 $C_{ss,avg}$ 为 2 mg/L[159]|$AUC_{ss,24h}$ 为 50 mg/L,L,对应 $C_{ss,avg}$ 为 2 mg/L[159]|$C_{min-ss}$ 和 $AUC_{0-24h}$ [135,161]|基于 TDM 结果个体化调整| |氟康唑|$C_{min-ss}$ 和 $AUC_{0-24h}$ [135,161]|$C_{min-ss}$ 和 $AUC_{0-24h}$ [135,161]|$C_{min-ss}$ 和 $AUC_{0-24h}$ [135,161]|$C_{min-ss}$ 和 $AUC_{0-24h}$ [135,161]|①$C_{min-ss}$ &lt;10×MIC,剂量上调25%②$C_{min-ss}$ &gt;50 mg/L,下调50%;$C_{min-ss}$ 为30~50 mg/L,下调25%[135]| |伏立康唑$^{c}$|$C_{min-ss}$ [72-75,150]|给予负荷剂量后3~5 d 进行首次采血[72,162]|①$C_{min-ss}$ 1.0~5.5 mg/L[73-74,163]②危重症患者抗真菌预防或治疗$C_{min-ss}$ 为2~6 mg/L[150]|加用或停用影响伏立康唑 PK 药物[72]|①$C_{min-ss}$ &lt;1.0 mg/L 且抗真菌治疗无反应时,剂量可增加50%或100%②$C_{min-ss}$ &gt;5.5 mg/L 或观察到药物相关不良反应时,剂量减少25%或50%以降低 $C_{min-ss}$ [73]| |泊沙康唑|$C_{min-ss}$ [150,164-165]|①口服混悬液:用药后7 d 进行首次采血②注射液或肠溶片:用药后5~7 d 进行首次采血[166]|①$C_{min-ss}$:预防真菌感染为≥0.5~0.7 mg/L(危重症患者为&gt;0.5~0.7 mg/L);抗真菌治疗&gt;1 mg/L[150,165]②儿童患者预防真菌感染 $C_{min-ss}$ 为≥0.7 mg/L[167]|加用或停用质子泵抑制剂等能影响泊沙康唑体内代谢的药物,应在更改方案7 d 后再次监测|基于 TDM 结果个体化调整| |艾沙康唑|$C_{min-ss}$ [135]|$C_{min-ss}$ 1~7 mg/L[135]||①$C_{min-ss}$ &gt;5 mg/L, 剂量下调25%~50%② $C_{min-ss}$ &lt;1 mg/L, 上调25%~50%[135]||

注:(1)TDM:治疗药物监测:$C_{ss}$:稳态血药浓度;$JC_{ss}$:连续给药游离稳态血药浓度;$MIC_{s}$:最低抑菌浓度;$%/T>MIC_{s}$:给药间隔内游离药物浓度高于MIC的时间百分比;$C_{min-ss}$:稳态血药谷浓度;$C_{max-ss}$:稳态血药峰浓度;AKI:急性肾损伤;$JC_{min}$:间歇给药游离谷浓度:$C_{min}$:谷浓度;$SMZ_{s}$:磺胺甲噁唑;TMP:甲氧苄啶;$AUC_{0-24h}$:24 h 药时曲线下面积;$AUC_{0-24h}$:游离药物24 h 药时曲线下面积;$MRS_{s}$:耐甲氧西林金黄色葡萄糖球菌;$AUC_{ss,24h}$:稳态下24 h 内的药时曲线下面积;$C_{ss,avg}$:稳态平均血药浓度;$PK_{s}$:药代动力学;PD:药效动力学。(2)$^{a}$表中未标明监测时机的;$C_{min-ss}$为下一次给药前30 min采样;$C_{max-ss}$为静脉输注结束后30~60 min采样;$C_{ss}$为连续输注的药物,达稳态后的任何时间点采样。$(3)^{b}$β内酰胺类$Uptodate$专题及部分指南文献推荐的最低PK/PD靶值目标为≥50%/T>MIC_{s}$;危重症患者首选PK/PD目标则提高至≥100%/T>MIC_{s}^{[98,121]}$,和其余文献推荐存在差异,建议PK/PD靶值应结合临床疗效和安全性进行个体化综合评估。(4)“所有药物重复监测时机的通用原则:①调整给药剂量或频率,应在3~5个半衰期后再次进行TDM评估;②发生药物不良事件和疗效欠佳者,随时复查。(5)$^{d}$亚胺培南稳定性差,建议采样后快速送检。$(6)^{e}$推荐常规TDM的抗菌药物。(7)表格为基于现有文献证据整理的TDM要点,临床实施时须充分权衡疗效与毒性风险,且谨慎超说明书用药,并依法履行知情同意。

参与本共识讨论和制订的专家（按单位汉语拼音排序）：

指导专家:深圳市儿童医院(陈泽彬);首都医科大学附属北京儿童医院(王晓玲)

临床专家:北京儿童医院黑龙江医院(哈尔滨市儿童医院)(于鑫岩);成都市妇女儿童中心医院(朱玲);重庆医科大学附属儿童医院(白科);大连市妇女儿童医疗中心(集团)(李宁);复旦大学附属儿科医院(陈伟明);广东省人民医院(郭予雄、王静);广州医科大学附属广州妇女儿童医疗中心(杨镱宇);河南省儿童医院(成怡冰、苏军);湖北省妇幼保健院(朱凤娜);湖南省儿童医院(黄娇甜);南京医科大学附属儿童医院(缪红军);山东大学附属儿童医院(林霞);上海交通大学医学院附属上海儿童医学中心(宁铂涛);深圳市儿童医院(杨卫国、马伟科、武宇辉、张蕾、贾实磊、王朝霞、苏国云、魏锋、李丹、卢平、陈俊宇、谢慧、范绮梦);首都医科大学附属北京儿童医院(钱索云、王荃、李峥、贾鑫磊、孙婧、巩纯秀);四川大学华西第二医院(李德渊);厦门市儿童医院(黄育坤)

药学专家:重庆医科大学附属儿童医院(贾运涛、邓冬梅);大连市妇女儿童医疗中心(集团)(李中、张奇);广东省妇幼保健院(方瑞);广州医科大学附属妇女儿童医疗中心(莫小兰、梁倩莹);哈尔滨医科大学附属第一医院(赵爽);河南省儿童医院(张胜男、海莉丽);湖南省儿童医院(赵昕、张海霞);南京医科大学附属儿童医院(陈峰、郭慧蕾);山东大学齐鲁医院(郑义);上海交通大学医学院附属上海儿童医学中心(李志玲、于丽婷);上海市儿童医院(王学彬);深圳市宝安区妇幼保健院(范晓梅);深圳市第二人民医院(王金平);深圳市儿童医院(陈泽彬、李学娟、文庆、段淑倪、崔萍、郭育鑫、湛敏);深圳市妇幼保健院(常宏、邓少洁);深圳市罗湖区妇幼保健院(许夏燕);首都医科大学附属北京儿童医院(王晓玲、杨梅);首都医科大学附属北京儿童医院黑龙江医院(哈尔滨市儿童医院)(金彦、李天姿);四川大学华西第二医院(林芸竹);苏州大学附属儿童医

院(周密);武汉儿童医院(刘茂昌、高萍);浙江大学医学院附属儿童医院(缪静、黄凌斐);浙江省肿瘤医院(杨佳钰);中山大学附属第八医院(刘新宇);中山大学附属第七医院(周本杰)

方法学专家:北京大学深圳医院(苏琪茹);首都医科大学附属北京儿童医院(彭晓霞);中山大学附属第七医院(袁金秋)

外审专家:安徽省儿童医院(蔡和平);天津市儿童医院(孙燕燕);西安市儿童医院(李媛、张华);中国医科大学附属盛京医院(刘春峰)

利益冲突所有作者声明不存在利益冲突

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(收稿日期:2025-11-20)

(本文编辑:李建华)

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