Whitby M, Finch R
Drugs. 1986 Mar;31(3):266-78. doi: 10.2165/00003495-198631030-00004.
Bacterial meningitis is a continuing challenge. This applies especially to infections in the neonate and the elderly, and to those which are hospital acquired. Factors which maintain the high morbidity and significant mortality from this disease include microbial virulence, a limited host response to infection within the cerebrospinal fluid (CSF), where phagocyte function is often impaired and complement and opsonic antibody activity are deficient, as well as delays in diagnosis and treatment. Added to these adverse factors is the pharmacokinetic hurdle of the 'blood-brain barrier', which limits drug concentrations achievable within the CSF. Inflammatory changes certainly improve the penetration of many agents, especially the penicillins and cephalosporins, but it must be remembered that with resolution of inflammation, achievable concentrations decline. Hence, the necessity for continuing parenteral administration of antibiotics throughout the treatment period. Although penicillin G (benzylpenicillin) remains the drug of choice for both pneumococcal and meningococcal infections, increasing resistance to ampicillin among Haemophilus influenzae has lead to greater reliance on alternative agents. Chloramphenicol is widely used, yet is potentially toxic, so that therapy with cefuroxime and the newer cephalosporins has been increasingly advocated. The advent of these potent, broad spectrum cephalosporins has induced a reappraisal of the treatment of Gram-negative bacillary meningitis, where ampicillin resistance and poor CSF penetration by the aminoglycosides have contributed to an unsatisfactory impact on outcome. Agents such as cefotaxime and ceftazidime have proved effective, although greater controlled experience is required. Finally, the contagious nature of meningococcal and H. influenzae infections justifies offering chemoprophylaxis to selected contacts, with rifampicin (or minocycline for contacts of patients with meningococcal infections).
细菌性脑膜炎仍然是一个持续存在的挑战。这尤其适用于新生儿和老年人的感染以及医院获得性感染。导致这种疾病高发病率和显著死亡率的因素包括微生物毒力、宿主对脑脊液（CSF）内感染的反应有限（其中吞噬细胞功能常常受损，补体和调理抗体活性不足），以及诊断和治疗的延迟。除了这些不利因素外，还有“血脑屏障”的药代动力学障碍，它限制了脑脊液中可达到的药物浓度。炎症变化肯定会提高许多药物的穿透力，尤其是青霉素类和头孢菌素类，但必须记住，随着炎症的消退，可达到的浓度会下降。因此，在整个治疗期间持续进行抗生素的胃肠外给药是必要的。虽然青霉素G（苄青霉素）仍然是肺炎球菌和脑膜炎球菌感染的首选药物，但流感嗜血杆菌对氨苄西林的耐药性增加，导致人们更多地依赖替代药物。氯霉素被广泛使用，但有潜在毒性，因此越来越多地提倡使用头孢呋辛和新型头孢菌素进行治疗。这些强效广谱头孢菌素的出现促使人们重新评估革兰氏阴性杆菌性脑膜炎的治疗，在这种疾病中，氨苄西林耐药以及氨基糖苷类药物在脑脊液中的穿透力差，对治疗结果产生了不理想的影响。头孢噻肟和头孢他啶等药物已被证明有效，尽管还需要更多的对照试验经验。最后，脑膜炎球菌和流感嗜血杆菌感染具有传染性，这证明对选定的接触者进行化学预防是合理的，可使用利福平（或对脑膜炎球菌感染患者的接触者使用米诺环素）。
