Nicasio Anthony M, Quintiliani Richard, DeRyke C Andrew, Kuti Joseph L, Nicolau David P
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT 06102, USA.
Ann Pharmacother. 2007 Jun;41(6):1077-81. doi: 10.1345/aph.1K060. Epub 2007 May 1.
To describe the use of and cerebral spinal fluid (CSF) penetration of a prolonged infusion meropenem regimen in a patient with Serratia marcescens meningitis.
A 54-year-old female was diagnosed with S. marcescens meningitis associated with an epidural abscess 57 days after surgery for a herniated spinal disk. Meropenem 2000 mg every 8 hours was administered as a prolonged (3 h) infusion for the purpose of optimizing pharmacodynamic exposure. Meropenem concentrations were measured from the patient's blood and CSF (via a lumbar drain). The prolonged infusion regimen resulted in concentrations in both serum and CSF above the meropenem minimum inhibitory concentration (MIC) of 0.047 microg/mL for 100% of the dosing interval. After 6 days of therapy, the patient showed no further signs of infection and was subsequently discharged to a rehabilitation facility. At follow-up, she had completed a 4 week course of the prolonged infused therapy without relapse or adverse events.
Gram-negative infections of the central nervous system result in high morbidity and mortality. These infections are often difficult to treat because of poor antibiotic penetration coupled with increasing antibiotic resistance. Although there are 2 other case reports that describe the use of prolonged infusion of meropenem, our patient had a lumbar drain in place, thereby allowing us to collect multiple CSF samples and more accurately assess meropenem exposure at the site of infection. CSF penetration was 6.4% in this patient, resulting in 100% time above the MIC throughout the dosing interval.
In this patient with meropenem-susceptible S. marcescens meningitis, the use of a high-dose prolonged infusion of meropenem resulted in adequate exposure at the site of infection and a successful clinical response.
描述延长输注美罗培南方案在粘质沙雷氏菌脑膜炎患者中的应用及脑脊液（CSF）穿透情况。
一名54岁女性在接受椎间盘突出症手术后57天被诊断为与硬膜外脓肿相关的粘质沙雷氏菌脑膜炎。为优化药效学暴露，每8小时给予2000mg美罗培南进行延长（3小时）输注。从患者血液和脑脊液（通过腰椎引流管）中测量美罗培南浓度。延长输注方案导致血清和脑脊液中的浓度在整个给药间隔期间100%高于美罗培南最低抑菌浓度（MIC）0.047μg/mL。治疗6天后，患者未出现进一步感染迹象，随后出院至康复机构。随访时，她已完成4周的延长输注治疗疗程，无复发或不良事件。
中枢神经系统革兰氏阴性感染导致高发病率和死亡率。由于抗生素穿透性差以及抗生素耐药性增加，这些感染通常难以治疗。尽管有另外2例病例报告描述了美罗培南的延长输注应用，但我们的患者放置了腰椎引流管，从而使我们能够收集多个脑脊液样本并更准确地评估感染部位的美罗培南暴露情况。该患者的脑脊液穿透率为6.4%，在整个给药间隔期间导致100%的时间高于MIC。
在这名对美罗培南敏感的粘质沙雷氏菌脑膜炎患者中，使用高剂量延长输注美罗培南导致感染部位有足够的暴露并取得了成功的临床反应。
