Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney Injury.
Finding the Dose for Ceftolozane-Tazobactam in Critically Ill Children with and without Acute Kidney Injury.
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确定头孢洛扎-他唑巴坦在有和无急性肾损伤的危重儿童中的剂量。
DOI：
10.3390/antibiotics9120887
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发表时间：
2020-12-10
期刊：
影响因子：
--
通讯作者：
Santiago MJ
中科院分区：
文献类型：
--
作者：
Butragueño-Laiseca L;Troconiz IF;Grau S;Campillo N;García X;Padilla B;Fernández SN;Santiago MJ
研究背景：头孢洛扎-他唑巴坦是一种新型抗生素，可对抗铜绿假单胞菌等多重耐药病原菌。头孢洛扎-他唑巴坦在儿童中的剂量仍不确定，特别是在肾损害或接受连续性肾脏替代治疗（CRRT）的儿童中。方法：对3例危重患儿采用不同的头孢洛扎-他唑巴坦给药方案进行评价。通过基于群体PK模型的贝叶斯估计获得患者的特定参数来表征头孢洛扎的药代动力学（PK）。同时使用前滤器、后滤器和超滤液浓度估计接受CRRT的患者C的清除率（CL）。将血液、透析液、置换液和超滤液流速以及红细胞压积等变量整合到模型中。使用NONMEM v.7.4进行所有PK分析。结果如下：患者A（8月龄，8.7 kg），肾功能正常，每6 h接受40 mg/kg：肾清除率（AUC）为0.88 L/h;分布容积（Vd）Vd 1 = 3.45 L，Vd 2 = 0.942 L;终末半衰期（t1/2，β）= 3.51 h，给药间隔稳态药物浓度-时间曲线下面积（AUCτ，SS）为397.73 mg × h × L−1。eGFR为22 mL/min/1.73 m2的患者B（19月龄，11 kg）接受36 mg/kg每8 h给药一次：AUC = 0.27 L/h; Vd 1 = 1.13 L; Vd 2 = 1.36; t1/2，β = 6.62 h; AUCSS 1481.48 mg × h × L−1。患者C（9月龄，5.8 kg）患有重度肾损害，接受CRRT治疗，接受30 mg/kg每8 h一次：肾脏替代治疗清除率（CLRRT）0.39 L/h; Vd 1 = 0.74 L; Vd 2 = 1.17; t1/2，β = 3.51 h; AUCτ，SS 448.72 mg × h × L−1。未观察到抗生素治疗引起的不良反应。结论：我们的研究结果表明，每8小时35 mg/kg的剂量可能是适当的重症脓毒症儿童与多药耐药铜绿假单胞菌感染。对于重度阿基儿童，可以考虑每8小时10 mg/kg的较低剂量。对于CRRT和高流出率的患者，可以考虑每8小时30 mg/kg的剂量。
Background: Ceftolozane-tazobactam is a new antibiotic against multidrug-resistant pathogens such as Pseudomonas aeruginosas. Ceftolozane-tazobactam dosage is still uncertain in children, especially in those with renal impairment or undergoing continuous renal replacement therapy (CRRT). Methods: Evaluation of different ceftolozane-tazobactam dosing regimens in three critically ill children. Ceftolozane pharmacokinetics (PK) were characterized by obtaining the patient’s specific parameters by Bayesian estimation based on a population PK model. The clearance (CL) in patient C undergoing CRRT was estimated using the prefilter, postfilter, and ultrafiltrate concentrations simultaneously. Variables such as blood, dialysate, replacement, and ultrafiltrate flow rates, and hematocrit were integrated in the model. All PK analyses were performed using NONMEM v.7.4. Results: Patient A (8 months of age, 8.7 kg) with normal renal function received 40 mg/kg every 6 h: renal clearance (CLR) was 0.88 L/h; volume of distribution (Vd) Vd1 = 3.45 L, Vd2 = 0.942 L; terminal halflife (t1/2,β) = 3.51 h, dosing interval area under the drug concentration vs. time curve at steady-state (AUCτ,SS) 397.73 mg × h × L−1. Patient B (19 months of age, 11 kg) with eGFR of 22 mL/min/1.73 m2 received 36 mg/kg every 8 h: CLR = 0.27 L/h; Vd1 = 1.13 L; Vd2 = 1.36; t1/2,β = 6.62 h; AUCSS 1481.48 mg × h × L−1. Patient C (9 months of age, 5.8 kg), with severe renal impairment undergoing CRRT received 30 mg/kg every 8 h: renal replacement therapy clearance (CLRRT) 0.39 L/h; Vd1 = 0.74 L; Vd2= 1.17; t 1/2,β = 3.51 h; AUCτ,SS 448.72 mg × h × L−1. No adverse effects attributable to antibiotic treatment were observed. Conclusions: Our results suggest that a dose of 35 mg/kg every 8 h can be appropriate in critically ill septic children with multi-drug resistance Pseudomonas aeruginosa infections. A lower dose of 10 mg/kg every 8 h could be considered for children with severe AKI. For patients with CRRT and a high effluent rate, a dose of 30 mg/kg every 8 h can be considered.
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影响因子：
2.9
作者：
Mian AN;Schwartz GJ
通讯作者：
Schwartz GJ
推荐的β-内酰胺方案对于接受连续肾脏替代治疗的脓毒症患者来说是不够的。
DOI：
10.1186/cc10257
发表时间：
2011
期刊：
Critical care (London, England)
影响因子：
--
作者：
Seyler L;Cotton F;Taccone FS;De Backer D;Macours P;Vincent JL;Jacobs F
通讯作者：
Jacobs F
影响因子：
4.9
作者：
Sime, Fekade B.;Lassig-Smith, Melissa;Roberts, Jason A.
通讯作者：
Roberts, Jason A.
影响因子：
1.7
作者：
Martin-Cazana, Maria;Grau, Santiago;Blazquez-Gamero, Daniel
通讯作者：
Blazquez-Gamero, Daniel
影响因子：
4.9
作者：
Sime, Fekade B.;Lassig-Smith, Melissa;Roberts, Jason A.
通讯作者：
Roberts, Jason A.