Alper C M, Doyle W J, Seroky J T, Bluestone C D
Department of Pediatric Otolaryngology, Children's Hospital of Pittsburgh, PA 15213, USA.
Antimicrob Agents Chemother. 1996 Aug;40(8):1889-92. doi: 10.1128/AAC.40.8.1889.
Because of the increasing frequencies of recovery of penicillin-resistant Streptococcus pneumoniae from the middle ears of children with acute otitis media, non-beta-lactam antibiotics are being explored as treatment alternatives to amoxicillin. In this study, the efficacy of a 10-day course of clarithromycin was evaluated with chinchillas. After the pharmacokinetic profiles for clarithromycin were established, 180 animals were assigned to one of three susceptibility groups (n = 60/group; penicillin-susceptible, -intermediate, and -resistant S. pneumoniae), and the right middle ear was infected with the appropriate strain of S. pneumoniae. Equal numbers of animals in each group were treated orally beginning on day 2 with a 10-day course of clarithromycin (15 mg/kg of body weight; given twice a day) or amoxicillin as a control (20 mg/kg twice a day). On days 4, 9, and 13, otomicroscopy and tympanometry were performed, and on day 13, the middle ears were cultured for bacteria. The results showed 100% eradication of the challenge organism in both treatment groups for the susceptible strains of S. pneumoniae. Cultures were negative in 87 and 74% (P > 0.05) of the animals challenged with the intermediate resistant strains and in 100 and 56% (P < 0.05) of the animals challenged with the resistant strains and treated with clarithromycin and amoxicillin, respectively. There were no differences between treatments in the diagnosis of effusion for any group. These results support the use of the chinchilla to evaluate drug efficacy in the treatment of acute otitis media and show clarithromycin to be effective in sterilizing the middle ears of animals challenged with penicillin-susceptible, -intermediate, and -resistant strains of S. pneumoniae.
由于从患有急性中耳炎的儿童中耳中分离出耐青霉素肺炎链球菌的频率不断增加,正在探索使用非β-内酰胺类抗生素作为阿莫西林的替代治疗药物。在本研究中,用龙猫评估了为期10天的克拉霉素疗程的疗效。确定克拉霉素的药代动力学特征后,将180只动物分为三个敏感性组之一(每组n = 60;青霉素敏感、中介和耐药肺炎链球菌),右中耳接种相应的肺炎链球菌菌株。从第2天开始,每组中数量相等的动物口服为期10天的克拉霉素疗程(15 mg/kg体重;每日两次)或阿莫西林作为对照(20 mg/kg每日两次)。在第4、9和13天进行耳显微镜检查和鼓室图测量,并在第13天对中耳进行细菌培养。结果显示,对于肺炎链球菌敏感菌株,两个治疗组中的攻击菌株均被100%根除。用中介耐药菌株攻击的动物中,87%和74%(P>0.05)的培养物为阴性;用耐药菌株攻击并用克拉霉素和阿莫西林治疗的动物中,分别有100%和56%(P<0.05)的培养物为阴性。任何组在积液诊断方面的治疗之间均无差异。这些结果支持使用龙猫评估急性中耳炎治疗中的药物疗效,并表明克拉霉素对于用青霉素敏感、中介和耐药肺炎链球菌菌株攻击的动物中耳消毒有效。