Klugman K P, Dagan R
Department of Medical Microbiology, University of Witwatersrand, South Africa.
Antimicrob Agents Chemother. 1995 May;39(5):1140-6. doi: 10.1128/AAC.39.5.1140.
Broad-spectrum cephalosporins are drugs of choice for the treatment of meningitis in communities which can afford them. The emergence of cephalosporin-resistant pneumococci demands the clinical trial of alternate agents. Carbapenems are active against the bacteria causing meningitis, but the use of imipenem-cilastatin was frustrated by drug-associated seizures. The safety and efficacy of meropenem, a new carbapenem, were compared to those of cefotaxime in a prospective randomized trial of 190 children with bacterial meningitis. Seizures occurred within 24 h before antibiotic therapy in 16 of 98 patients (16%) randomized to receive meropenem and in 6 of 92 patients (7%) randomized to receive cefotaxime. In patients without seizures before therapy, seizures occurred during therapy in 5 of 82 patients (6%) receiving meropenem and in 1 of 86 patients (1%) receiving cefotaxime (95% confidence interval: -0.7%, 10.6%). None were thought to be drug related. Twenty-four meropenem-treated patients (24%) and 11 cefotaxime-treated patients (12%) had neurological abnormalities before therapy. In patients without pretherapy neurological abnormalities, these abnormalities were present after treatment in 4 of 74 meropenem-treated patients (5%) and in 2 of 81 cefotaxime-treated patients (2%) (95% confidence interval: -3.2%, 9.1%). Of 75 meropenem-treated and 64 cefotaxime-treated patients with pretherapy positive cerebrospinal-fluid cultures, 68 and 59, respectively, had repeat lumbar punctures. Bacterial eradication was found to be 100% in both groups. Our data suggest that meropenem may be a carbapenem agent that is well tolerated and effective in the treatment of bacterial meningitis.
在负担得起的社区中,广谱头孢菌素是治疗脑膜炎的首选药物。耐头孢菌素肺炎球菌的出现需要对替代药物进行临床试验。碳青霉烯类药物对引起脑膜炎的细菌有活性,但亚胺培南-西司他丁的使用因药物相关的癫痫发作而受阻。在一项针对190例细菌性脑膜炎儿童的前瞻性随机试验中,将新型碳青霉烯类药物美罗培南与头孢噻肟的安全性和有效性进行了比较。在随机接受美罗培南治疗的98例患者中,有16例(16%)在抗生素治疗前24小时内发生癫痫发作;在随机接受头孢噻肟治疗的92例患者中,有6例(7%)发生癫痫发作。在治疗前无癫痫发作的患者中,接受美罗培南治疗的82例患者中有5例(6%)在治疗期间发生癫痫发作,接受头孢噻肟治疗的86例患者中有1例(1%)发生癫痫发作(95%置信区间:-0.7%,10.6%)。均认为与药物无关。24例接受美罗培南治疗的患者(24%)和11例接受头孢噻肟治疗的患者(12%)在治疗前有神经异常。在治疗前无神经异常的患者中,接受美罗培南治疗的74例患者中有4例(5%)在治疗后出现这些异常,接受头孢噻肟治疗的81例患者中有2例(2%)出现这些异常(95%置信区间:-3.2%,9.1%)。在75例接受美罗培南治疗和64例接受头孢噻肟治疗且治疗前脑脊液培养阳性的患者中,分别有68例和59例进行了重复腰椎穿刺。两组细菌清除率均为100%。我们的数据表明,美罗培南可能是一种耐受性良好且对治疗细菌性脑膜炎有效的碳青霉烯类药物。