Cies Jeffrey J, LaCoursiere Richard J, Moore Wayne S, Chopra Arun
The Center for Pediatric Pharmacotherapy (JJC, WSM, AC), LLC, Pottstown, Pennsylvania; St. Christopher's Hospital for Children (JJC), Philadelphia, Pennsylvania; Drexel University College of Medicine (JJC), Philadelphia, Pennsylvania; Thomas Jefferson University School of Pharmacy (RJL), Philadelphia, Pennsylvania; NYU Langone Medical Center (AC), New York, New York; NYU School of Medicine (AC), New York, New York.
J Pediatr Pharmacol Ther. 2017 Nov-Dec;22(6):467-470. doi: 10.5863/1551-6776-22.6.467.
Aztreonam, a broad-spectrum monobactam, is typically reserved for multidrug resistant (MDR) infections. Pharmacokinetic (PK) data to guide dosing in children, however, are limited to healthy volunteers or nonintensive care unit (ICU) patients. Impaired antibiotic delivery into tissue remains a major concern and may explain the high morbidity and mortality associated with MDR infections. Therefore, evaluating the PK changes in pediatric ICU patients is necessary to elucidate the most appropriate antimicrobial regimen. We describe the PK of prolonged infusion aztreonam in a patient with MDR Pseudomonas aeruginosa empyema. The 16-year-old tetraplegic male with a cervical spinal cord injury, chronic respiratory failure, and tracheostomy was admitted with a 2-day history of fever and hypoxemia. Chest x-ray revealed a left lower lobe infiltrate. On hospital day 2, computed tomography scan noted a massive collapse of the left lung with bronchiectasis and hepatization with a pneumatocele. He underwent bronchoscopy on days 2, 6, and 10 and the cultures subsequently grew P aeruginosa only sensitive to aztreonam (minimum inhibitory concentration [MIC] of 2-6 mg/L). A regimen of aztreonam 2 grams intravenously (IV) every 6 hours (each dose infused over 4 hours) and polymyxin B 1,000,000 units IV every 12 hours (each dose infused over 30 minutes) was initiated on day 3. On day 8, the aztreonam serum plateau concentration was 71 mg/L. Repeat respiratory and bronchoscopy cultures from days 19 to 37 remained negative. Aztreonam clearance was 2.3 mL/kg/min, which was significantly increased when compared with the 1.3 mL/kg/min suggested in the prescribing information based on adult data. A prolonged infusion of 2 grams of aztreonam every 6 hours (each dose infused over 4 hours) successfully attained 100% of the target serum and lung concentrations above the MIC for at least 40% of the dosing interval, and was associated with successful treatment of MDR P aeruginosa empyema.
氨曲南是一种广谱单环β-内酰胺类抗生素，通常用于治疗多重耐药（MDR）感染。然而，用于指导儿童用药剂量的药代动力学（PK）数据仅限于健康志愿者或非重症监护病房（ICU）患者。抗生素向组织内的递送受损仍然是一个主要问题，这可能解释了与MDR感染相关的高发病率和死亡率。因此，评估儿科ICU患者的PK变化对于阐明最合适的抗菌方案是必要的。我们描述了在一名患有MDR铜绿假单胞菌脓胸患者中延长输注氨曲南的PK情况。该16岁男性四肢瘫痪患者，有颈髓损伤、慢性呼吸衰竭和气管造口术，因发热和低氧血症2天入院。胸部X线显示左下叶浸润。住院第2天，计算机断层扫描显示左肺大量萎陷，伴有支气管扩张和肝样变，并伴有肺气囊。他在第2天、第6天和第10天接受了支气管镜检查，随后培养结果显示仅对氨曲南敏感的铜绿假单胞菌生长（最低抑菌浓度[MIC]为2 - 6mg/L）。第3天开始使用每6小时静脉注射（IV）2克氨曲南（每次剂量输注4小时）和每12小时静脉注射100万单位多粘菌素B（每次剂量输注30分钟）的方案。第8天，氨曲南血清平台浓度为71mg/L。第19天至37天重复进行的呼吸道和支气管镜培养结果均为阴性。氨曲南清除率为2.3 mL/kg/min，与基于成人数据的处方信息中建议的1.3 mL/kg/min相比显著增加。每6小时延长输注2克氨曲南（每次剂量输注4小时）成功使目标血清和肺浓度在至少40%的给药间隔内达到高于MIC的100%，并成功治疗了MDR铜绿假单胞菌脓胸。
