Nelson J D
Am J Med. 1985 Aug 9;79(2A):47-51. doi: 10.1016/0002-9343(85)90260-8.
Since 1974, ampicillin and chloramphenicol have been standard therapeutic agents for initial treatment of bacterial meningitis occurring after the newborn period. Emerging problems necessitate a reappraisal and a search for alternatives to those drugs. The problems include the following: (1) Some strains of pneumococci (between 3 and 16 percent) are relatively resistant, with minimal inhibitory concentrations between 0.1 and 1.0 microgram/ml) to penicillin G and ampicillin. Such strains are not eradicated from the cerebrospinal fluid by the usual dosages of penicillin G or ampicillin. (2) Some strains of Hemophilus influenzae type B are resistant to ampicillin and chloramphenicol by virtue of beta-lactamase and acetyltransferase production. Such strains are currently rare in the United States, but it has been predicted that they might account for as many as one quarter of the isolates within a few years. (In Barcelona, Spain, their prevalence is 18 percent.) (3) Patients with meningitis often receive phenobarbital or phenytoin. Those drugs, and others metabolized by the liver, can significantly affect the pharmacology of chloramphenicol and result in either subtherapeutic or toxic concentrations of chloramphenicol in some patients. (4) For a variety of reasons, neither ampicillin plus gentamicin nor ampicillin plus chloramphenicol is an ideal combination for infants between one and four months of age when etiologic agents include coliform bacilli and group B streptococci, as well as Hemophilus, pneumococci, and meningococci. First-generation cephalosporins were unsuitable for the treatment of meningitis because of their low concentrations in the cerebrospinal fluid in relation to the bactericidal concentrations required for the common pathogens. Several of the newer cephalosporins achieve therapeutic concentrations in the cerebrospinal fluid and, in the case of three cephalosporin derivatives (cefuroxime, cefotaxime, and moxalactam), large, controlled clinical trials have demonstrated activity comparable to that of standard therapy. Limited experience suggests that several other cephalosporins (e.g., ceftizoxime, ceftazidime) will be shown to be effective when more experience is gained. Furthermore, the use of these drugs, with the exception of moxalactam, which has insufficient activity against gram-positive cocci, obviates the four problems just cited.
自1974年以来，氨苄西林和氯霉素一直是新生儿期后发生的细菌性脑膜炎初始治疗的标准治疗药物。新出现的问题需要重新评估并寻找这些药物的替代药物。这些问题包括：（1）一些肺炎球菌菌株（3%至16%）对青霉素G和氨苄西林相对耐药，最低抑菌浓度在0.1至1.0微克/毫升之间。常规剂量的青霉素G或氨苄西林无法从脑脊液中清除这些菌株。（2）一些B型流感嗜血杆菌菌株通过产生β-内酰胺酶和乙酰转移酶而对氨苄西林和氯霉素耐药。目前在美国这种菌株很少见，但据预测，几年内它们可能占分离株的四分之一之多。（在西班牙巴塞罗那，其流行率为18%。）（3）脑膜炎患者常接受苯巴比妥或苯妥英治疗。这些药物以及其他经肝脏代谢的药物会显著影响氯霉素的药理学特性，导致一些患者体内氯霉素浓度低于治疗水平或出现毒性浓度。（4）由于多种原因，当病因包括大肠埃希菌、B组链球菌以及嗜血杆菌、肺炎球菌和脑膜炎球菌时，氨苄西林加庆大霉素或氨苄西林加氯霉素都不是1至4个月婴儿的理想联合用药方案。第一代头孢菌素不适合用于治疗脑膜炎，因为相对于常见病原体所需的杀菌浓度，它们在脑脊液中的浓度较低。几种较新的头孢菌素可在脑脊液中达到治疗浓度，并且就三种头孢菌素衍生物（头孢呋辛、头孢噻肟和拉氧头孢）而言，大型对照临床试验已证明其活性与标准治疗相当。有限的经验表明，当积累更多经验时，其他几种头孢菌素（如头孢唑肟、头孢他啶）也将被证明是有效的。此外，除了对革兰氏阳性球菌活性不足的拉氧头孢外，使用这些药物可避免上述四个问题。
