Boak Lauren M, Li Jian, Spelman Denis, du Cros Philipp, Nation Roger L, Rayner Craig R
Facility for Anti-infective Drug Development and Innovation, Department of Pharmacy Practice, Victorian College of Pharmacy, Monash University, Parkville, Australia.
Ann Pharmacother. 2006 Jul-Aug;40(7-8):1451-5. doi: 10.1345/aph.1H029. Epub 2006 Jun 13.
To describe a case of coagulase-negative Staphylococcus ventriculitis successfully treated with oral linezolid, for which good cerebrospinal fluid (CSF) penetration was observed.
A 69-year-old man had an extraventricular drain inserted following a right cerebellar infarct. On day 6, the CSF culture was positive for coagulase-negative staphylococci; intravenous vancomycin 1 g daily was initiated to treat ventriculitis. A ventriculoperitoneal shunt, inserted on day 35 to manage communicating hydrocephalus, was subsequently removed as symptoms suggesting infection presented. Coagulase-negative Staphylococcus was isolated from shunt reservoir aspirate, and intrathecal vancomycin 10 mg daily was added to the treatment regimen. On day 61, vancomycin was stopped and oral linezolid 600 mg twice daily was started. Linezolid was discontinued 22 days later, with no evidence of ongoing infection. Four blood samples were collected around the seventh dose of linezolid and 5 CSF samples were collected on separate days during treatment. Linezolid concentrations were measured in plasma and CSF by HPLC. Using an ADAPT II maximum a priori Bayesian estimator module, a 2 compartment pharmacokinetic model was fitted to the plasma linezolid concentration data and CSF:predicted plasma concentration ratios (ranging from 0.27 to 1.02) were derived. All CSF concentrations exceeded the reported 90% minimum inhibitory concentration of 2 mg/L for linezolid against coagulase-negative staphylococci.
Evidence of the effectiveness of linezolid against central nervous system infections is growing; however, limited data exist describing its CSF penetration. Oral linezolid exhibited good CSF penetration in this patient, which corresponded to positive clinical response.
Oral linezolid may play a valuable role in the treatment of multiresistant gram-positive central nervous system infections.
描述1例经口服利奈唑胺成功治疗的凝固酶阴性葡萄球菌性脑室炎病例,观察到该药在脑脊液(CSF)中有良好的穿透性。
1名69岁男性在发生右小脑梗死之后插入了脑室外引流管。第6天,CSF培养显示凝固酶阴性葡萄球菌阳性;开始每日静脉注射1g万古霉素以治疗脑室炎。第35天插入脑室腹腔分流管以处理交通性脑积水,随后因出现提示感染的症状而将其移除。从分流管储液器吸出物中分离出凝固酶阴性葡萄球菌,治疗方案中添加了每日10mg鞘内注射万古霉素。第61天,停用万古霉素,开始每日2次口服600mg利奈唑胺。22天后停用利奈唑胺,无持续感染的迹象。在利奈唑胺第7剂给药前后采集了4份血样,并在治疗期间不同日期采集了5份CSF样本。采用高效液相色谱法测定血浆和CSF中的利奈唑胺浓度。使用ADAPT II最大先验贝叶斯估计模块,将二室药代动力学模型拟合至血浆利奈唑胺浓度数据,并得出CSF与预测血浆浓度之比(范围为0.27至1.02)。所有CSF浓度均超过已报道的利奈唑胺针对凝固酶阴性葡萄球菌的90%最低抑菌浓度2mg/L。
利奈唑胺治疗中枢神经系统感染有效性的证据日益增多;然而,描述其CSF穿透性的数据有限。口服利奈唑胺在该患者中显示出良好的CSF穿透性,这与积极的临床反应相符。
口服利奈唑胺在治疗多重耐药革兰氏阳性菌中枢神经系统感染中可能发挥重要作用。