Cies Jeffrey J, Moore Wayne S, Conley Susan B, Dickerman Mindy J, Small Christine, Carella Dominick, Shea Paul, Parker Jason, Chopra Arun
The Center for Pediatric Pharmacotherapy LLC, Pottstown, Pennsylvania ; St. Christopher's Hospital for Children, Philadelphia, Pennsylvania ; Drexel University College of Medicine, Philadelphia, Pennsylvania.
The Center for Pediatric Pharmacotherapy LLC, Pottstown, Pennsylvania.
J Pediatr Pharmacol Ther. 2016 Jan-Feb;21(1):92-7. doi: 10.5863/1551-6776-21.1.92.
Pharmacokinetic parameters can be significantly altered for both extracorporeal life support (ECLS) and continuous renal replacement therapy (CRRT). This case report describes the pharmacokinetics of continuous-infusion meropenem in a patient on ECLS with concurrent CRRT. A 2.8-kg, 10-day-old, full-term neonate born via spontaneous vaginal delivery presented with hypothermia, lethargy, and a ~500-g weight loss from birth. She progressed to respiratory failure on hospital day 2 (HD 2) and developed sepsis, disseminated intravascular coagulation, and liver failure as a result of disseminated adenoviral infection. By HD 6, acute kidney injury was evident, with progressive fluid overload >1500 mL (+) for the admission. On HD 6 venoarterial ECLS was instituted for lung protection and fluid removal. On HD 7 she was initiated on CRRT. On HD 12, a blood culture returned positive and subsequently grew Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) for meropenem of 0.25 mg/L. She was started on vancomycin, meropenem, and amikacin. A meropenem bolus of 40 mg/kg was given, followed by a continuous infusion of 10 mg/kg/hr (240 mg/kg/day). On HD 15 (ECLS day 9) a meropenem serum concentration of 21 mcg/mL was obtained, corresponding to a clearance of 7.9 mL/kg/min. Repeat cultures from HDs 13 to 15 (ECLS days 7-9) were sterile. This meropenem regimen was successful in providing a target attainment of 100% for serum concentrations above the MIC for ≥40% of the dosing interval and was associated with a sterilization of blood in this complex patient on concurrent ECLS and CRRT circuits.
体外生命支持(ECLS)和持续肾脏替代疗法(CRRT)均可显著改变药代动力学参数。本病例报告描述了一名接受ECLS并同时进行CRRT的患者持续输注美罗培南的药代动力学情况。一名2.8千克、10日龄、足月顺产的新生儿,出生后出现体温过低、嗜睡,出生体重减轻约500克。出生后第2天(HD 2)病情进展为呼吸衰竭,并因播散性腺病毒感染出现败血症、弥散性血管内凝血和肝功能衰竭。至HD 6时,急性肾损伤明显,入院时液体超负荷进展超过1500毫升(+)。HD 6时开始进行静脉-动脉ECLS以保护肺部并清除液体。HD 7时开始进行CRRT。HD 12时,血培养结果呈阳性,随后培养出铜绿假单胞菌,其对美罗培南的最低抑菌浓度(MIC)为0.25毫克/升。开始给予万古霉素、美罗培南和阿米卡星治疗。给予40毫克/千克的美罗培南负荷剂量,随后以10毫克/千克/小时(240毫克/千克/天)持续输注。HD 15(ECLS第9天)时测得美罗培南血清浓度为21微克/毫升,相应清除率为7.9毫升/千克/分钟。HD 13至15(ECLS第7 - 9天)的重复培养均无菌。该美罗培南治疗方案成功使血清浓度在给药间隔的≥40%时间内达到高于MIC的目标值100%,并使该同时接受ECLS和CRRT治疗的复杂患者的血液实现了杀菌。