Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, An der Lutter 24, D-37075 Göttingen, Germany.
Clin Microbiol Rev. 2010 Oct;23(4):858-83. doi: 10.1128/CMR.00007-10.
The entry of anti-infectives into the central nervous system (CNS) depends on the compartment studied, molecular size, electric charge, lipophilicity, plasma protein binding, affinity to active transport systems at the blood-brain/blood-cerebrospinal fluid (CSF) barrier, and host factors such as meningeal inflammation and CSF flow. Since concentrations in microdialysates and abscesses are not frequently available for humans, this review focuses on drug CSF concentrations. The ideal compound to treat CNS infections is of small molecular size, is moderately lipophilic, has a low level of plasma protein binding, has a volume of distribution of around 1 liter/kg, and is not a strong ligand of an efflux pump at the blood-brain or blood-CSF barrier. When several equally active compounds are available, a drug which comes close to these physicochemical and pharmacokinetic properties should be preferred. Several anti-infectives (e.g., isoniazid, pyrazinamide, linezolid, metronidazole, fluconazole, and some fluoroquinolones) reach a CSF-to-serum ratio of the areas under the curves close to 1.0 and, therefore, are extremely valuable for the treatment of CNS infections. In many cases, however, pharmacokinetics have to be balanced against in vitro activity. Direct injection of drugs, which do not readily penetrate into the CNS, into the ventricular or lumbar CSF is indicated when other effective therapeutic options are unavailable.
抗感染药物进入中枢神经系统（CNS）取决于所研究的隔室、分子大小、电荷、亲脂性、血浆蛋白结合、与血脑/血脑脊液（CSF）屏障上主动转运系统的亲和力以及宿主因素，如脑膜炎症和 CSF 流。由于人类的微透析液和脓肿中的浓度并不经常可用，因此本综述重点介绍药物 CSF 浓度。治疗 CNS 感染的理想化合物是具有小分子量、中等亲脂性、低血浆蛋白结合率、分布容积约为 1 升/公斤、并且不是血脑或血-CSF 屏障上外排泵的强配体的化合物。当有几种同样有效的化合物可用时，应优先选择接近这些理化和药代动力学特性的药物。一些抗感染药物（例如异烟肼、吡嗪酰胺、利奈唑胺、甲硝唑、氟康唑和一些氟喹诺酮类药物）达到接近 1.0 的 CSF-血清曲线下面积比值，因此对于治疗 CNS 感染非常有价值。然而，在许多情况下，药代动力学必须与体外活性相平衡。当其他有效治疗选择不可用时，应将不易穿透 CNS 的药物直接注入脑室或腰椎 CSF 中。
