Schmutzhard E, Williams K J, Vukmirovits G, Chmelik V, Pfausler B, Featherstone A
University Clinic of Innsbruck, Austria.
J Antimicrob Chemother. 1995 Jul;36 Suppl A:85-97. doi: 10.1093/jac/36.suppl_a.85.
Third-generation cephalosporins are presently the agents of choice for the empirical antimicrobial therapy of bacterial meningitis. However, a number of factors associated with these agents, namely the development of resistance by pneumococci, limited activity against some Enterobacteriaceae and Pseudomonas spp., and the possible adverse effects of their bacteriolytic mode of action, indicate that newer classes of antimicrobial agents be evaluated for the treatment of bacterial meningitis. Meropenem is a carbapenem antibiotic which is highly active against the major bacterial pathogens causing meningitis, and penetrates well into the cerebrospinal fluid. Two prospective randomised studies in 56 adult bacterial meningitis patients have compared meropenem 40 mg/kg 8-hourly, up to a maximum of 6 g/day (n = 28) with cephalosporin treatment, i.e. cefotaxime (n = 17) or ceftriaxone (n = 11). Patients were assessed by neurological examination, Glasgow Coma Score and Herson-Todd score. Clinical cure was observed in all 23 evaluable patients treated with meropenem (100%) and with 17 of the 22 evaluable cephalosporin-treated patients (77%). All pre-treatment isolates were eradicated except one isolate of Staphylococcus aureus in a cefotaxime-treated patient. Neurological sequelae were noted in three meropenem and four cephalosporin-treated patients. No patients in either treatment group experienced seizures after the start of therapy. This was despite the fact that a patient in each group had experienced seizures before therapy, several had underlying CNS disorders, and that doses of 6 g/day of meropenem were given. Hearing impairment was recorded in 11 meropenem and nine cephalosporin treated patients. Three patients in the meropenem group and one in the cephalosporin group died during treatment for reasons unrelated to study therapy. Overall, the results of this study indicate that meropenem is an effective and well-tolerated antibiotic for the treatment of bacterial meningitis in adults.
第三代头孢菌素目前是细菌性脑膜炎经验性抗菌治疗的首选药物。然而，与这些药物相关的一些因素，即肺炎球菌耐药性的产生、对某些肠杆菌科细菌和假单胞菌属的活性有限，以及其溶菌作用方式可能产生的不良反应，表明需要评估新型抗菌药物用于治疗细菌性脑膜炎。美罗培南是一种碳青霉烯类抗生素，对引起脑膜炎的主要细菌病原体具有高度活性，并且能很好地穿透脑脊液。两项针对56例成年细菌性脑膜炎患者的前瞻性随机研究，将每8小时静脉滴注40mg/kg美罗培南（最大剂量为6g/天）（n = 28）与头孢菌素治疗进行了比较，即头孢噻肟（n = 17）或头孢曲松（n = 11）。通过神经学检查、格拉斯哥昏迷评分和赫森-托德评分对患者进行评估。接受美罗培南治疗的所有23例可评估患者（100%）以及接受头孢菌素治疗的22例可评估患者中的17例（77%）观察到临床治愈。除了一名接受头孢噻肟治疗的患者中的一株金黄色葡萄球菌分离株外，所有治疗前的分离株均被清除。在接受美罗培南治疗的3例患者和接受头孢菌素治疗的4例患者中发现有神经后遗症。两个治疗组中均没有患者在治疗开始后出现癫痫发作。尽管每组中有一名患者在治疗前曾有癫痫发作，数名患者有潜在的中枢神经系统疾病，并且给予了6g/天的美罗培南剂量。在接受美罗培南治疗的11例患者和接受头孢菌素治疗的9例患者中记录到听力损害。美罗培南组有3例患者和头孢菌素组有1例患者在治疗期间因与研究治疗无关的原因死亡。总体而言，本研究结果表明美罗培南是治疗成人细菌性脑膜炎的一种有效且耐受性良好的抗生素。
