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莫西沙星的治疗药物监测以指导极低出生体重儿脑膜炎的治疗

Therapeutic Drug Monitoring of Moxifloxacin to Guide Treatment of Meningitis in an Extremely Preterm Infant.

作者信息

Yeung Telford, Chung Erin, Chen Jennifer, Erdman Laura K, Smiljkovic Mina, Wong Waison, Rolnitsky Asaph, Morris Shaun K, El Shahed Amr, Banihani Rudaina, Bitnun Ari, Tomlinson Christopher

出版信息

J Pediatr Pharmacol Ther. 2021;26(8):857-862. doi: 10.5863/1551-6776-26.8.857. Epub 2021 Nov 10.

DOI:10.5863/1551-6776-26.8.857
PMID:34790077
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8592008/
Abstract

() is a rare cause of neonatal bacterial meningitis. Treatment can be challenging because of ' intrinsic antibiotic resistance and the difficulty in accessing antimicrobial susceptibility testing. In this report, we describe an extremely preterm male infant with seizures who had a subsequent diagnosis of meningitis. Because of severity of illness, doxycycline (4 mg/kg IV every 24 hours) and moxifloxacin (5 mg/kg IV every 24 hours) were started empirically. Repeat cerebrospinal fluid cultures were negative and showed decreasing pleiocytosis. Given the concentration-dependent killing of moxifloxacin and concern for endovascular infection from a concomitant cerebral venous sinus thrombosis, serum concentrations of moxifloxacin were obtained to estimate pharmacokinetic and pharmacodynamic parameters. These were compared to the targets described in other case reports of meningitis. The maximum serum concentration (C) was 2.5 mg/L, volume of distribution was 2.2 L/kg, clearance was 0.18 L/kg/hr, terminal half-life was 8.6 hours, and area-under-the-concentration-time curve (AUC) was 28.1 mg•hr/L. Using the range of minimum inhibitory concentrations (MICs) reported in the literature, the estimated C/MIC for this patient was 21 to 158 (target C/MIC: >10) and AUC/MIC was 234 to 1757 (target AUC/MIC: ≥100). Doxycycline and moxifloxacin were continued for 6 weeks. No adverse events to moxifloxacin or doxycycline were observed in the NICU. This report describes the successful treatment of neonatal meningitis and adds to the knowledge of pharmacokinetic and pharmacodynamic parameters of moxifloxacin in neonates. Additional data will help to confirm the role for routine therapeutic drug monitoring of moxifloxacin in neonates.

摘要

()是新生儿细菌性脑膜炎的罕见病因。由于其固有的抗生素耐药性以及进行抗菌药物敏感性测试的困难,治疗具有挑战性。在本报告中,我们描述了一名患有癫痫的极早产男婴,随后被诊断为脑膜炎。由于病情严重,经验性地开始使用多西环素(每24小时静脉注射4mg/kg)和莫西沙星(每24小时静脉注射5mg/kg)。重复脑脊液培养结果为阴性,且显示细胞数减少。鉴于莫西沙星的浓度依赖性杀菌作用以及对伴随的脑静脉窦血栓形成导致血管内感染的担忧,测定了莫西沙星的血清浓度以评估药代动力学和药效学参数。将这些参数与其他脑膜炎病例报告中描述的目标进行了比较。最大血清浓度(Cmax)为2.5mg/L,分布容积为2.2L/kg,清除率为0.18L/kg/小时,终末半衰期为8.6小时,浓度-时间曲线下面积(AUC)为28.1mg•hr/L。使用文献报道的最低抑菌浓度(MIC)范围,该患者的估计Cmax/MIC为21至158(目标Cmax/MIC:>10),AUC/MIC为234至1757(目标AUC/MIC:≥100)。多西环素和莫西沙星持续使用6周。在新生儿重症监护病房未观察到莫西沙星或多西环素的不良事件。本报告描述了新生儿脑膜炎的成功治疗,并增加了新生儿莫西沙星药代动力学和药效学参数的知识。更多数据将有助于确认莫西沙星在新生儿中进行常规治疗药物监测的作用。