Duke Trevor, Curtis Nigel, Fuller David G
Centre for International Child Health, University Department of Paediatrics, Royal Children's Hospital, Flemington Road, Parkville, Victoria, 3052, Australia.
Expert Opin Pharmacother. 2003 Aug;4(8):1227-40. doi: 10.1517/14656566.4.8.1227.
Bacterial meningitis is still a major cause of death and disability in children worldwide. With the advent of conjugate vaccines against the three major pathogens, the burden of disease is increasingly concentrated in developing countries that cannot afford the vaccines. Antibiotic resistance is an increasing problem; in developed countries, high-level resistance to beta-lactams among Streptococcus pneumoniae necessitates the addition of vancomycin to third-generation cephalosporins. In many developing countries, the problems are more fundamental. Increasing resistance of S. pneumoniae to penicillin and chloramphenicol and of Haemophilus influenzae to chloramphenicol means that many children with bacterial meningitis receive ineffective treatments, as third-generation cephalosporins are often unavailable or unaffordable. Case fatality rates are as high as 50% and neurological sequelae occur in one-third of survivors. The use of corticosteroids in meningitis is controversial; the evidence that they protect against neurological complications of childhood meningitis (particularly severe hearing loss) is strongest when: meningitis is caused by H. influenzae type b; dexamethasone is given before the first dose of antibiotics; a bactericidal antibiotic such as a third-generation cephalosporin is used; and in the early stages of the infection. There are few controlled clinical trials on which to base recommendations about other adjuvant therapy for meningitis. Avoidance of secondary brain injury from hypoxia, hypotension, hypo-osmolarity and cerebral oedema, hypoglycaemia or convulsions is essential for a good outcome. The problem of bacterial meningitis will only be solved if protein-conjugate vaccines (or other effective vaccine strategies) against S. pneumonia, H. influenzae and epidemic strains of Neisseria meningitidis are available to all the world's children. Making third-generation cephalosporins affordable in the developing world is also a necessary intervention, but better antibiotics will not overcome the problems of poor access to hospitals and late presentation with established brain injury, and will inevitably bring further pressure for antimicrobial resistance.
细菌性脑膜炎仍是全球儿童死亡和残疾的主要原因。随着针对三种主要病原体的结合疫苗的出现，疾病负担越来越集中在买不起疫苗的发展中国家。抗生素耐药性问题日益严重；在发达国家，肺炎链球菌对β-内酰胺类药物的高水平耐药性使得在第三代头孢菌素中添加万古霉素成为必要。在许多发展中国家，问题更为根本。肺炎链球菌对青霉素和氯霉素以及流感嗜血杆菌对氯霉素的耐药性不断增加，这意味着许多患细菌性脑膜炎的儿童接受的是无效治疗，因为第三代头孢菌素往往无法获得或负担不起。病死率高达50%，三分之一的幸存者会出现神经后遗症。在脑膜炎中使用皮质类固醇存在争议；当满足以下条件时，它们预防儿童脑膜炎神经并发症（尤其是严重听力损失）的证据最为充分：脑膜炎由b型流感嗜血杆菌引起；在首剂抗生素给药前给予地塞米松；使用杀菌性抗生素如第三代头孢菌素；以及在感染早期。关于脑膜炎其他辅助治疗的建议几乎没有基于对照临床试验。避免因缺氧、低血压、低渗透压和脑水肿、低血糖或惊厥导致的继发性脑损伤对于取得良好预后至关重要。只有当全世界所有儿童都能获得针对肺炎链球菌、流感嗜血杆菌和脑膜炎奈瑟菌流行菌株的蛋白质结合疫苗（或其他有效疫苗策略）时，细菌性脑膜炎问题才能得到解决。在发展中国家使第三代头孢菌素价格可承受也是一项必要的干预措施，但更好的抗生素无法克服就医不便和已发生脑损伤时就诊延迟的问题，而且不可避免地会给抗菌药物耐药性带来进一步压力。
