Granizo Juan José, Giménez María José, Barberán José, Coronel Pilar, Gimeno Mercedes, Aguilar Lorenzo
Clinical Epidemiology Department, Fundación Jiménez Díaz, Madrid, Spain.
Clin Ther. 2006 Dec;28(12):2061-9. doi: 10.1016/j.clinthera.2006.12.010.
Community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB) are frequently caused by Streptococcus pneumoniae, Haemopbilus influenzae, and Moraxella catarrbalis; thus, these are the target pathogens for antibiotic treatment.
This pooled analysis was performed to evaluate the efficacy of cefditoren pivoxil (CDN) in patients with lower respiratory tract infections (CAP or AECB). A particular focus was the per-pathogen bacteriologic response rate among the most common causative pathogens, S pneumoniae, H influenzae, and M catarrbalis.
The final reports of all clinical trials of CDN in the treatment of community-acquired lower respiratory tract infection were reviewed. Microbiologic outcome data for CDN 200 and 400 mg and comparator treatments were pooled from 4 CAP studies (3 randomized and 1 noncomparative) and 3 AECB studies. The comparators were the standard oral treatments clarithromycin 500 mg BID, cefuroxime 250 mg BID, cefpodoxime 200 mg BID, and amoxicillin/clavulanate 500/125 mg TID or 875/125 mg BID. Microbiologic response was defined as eradication of the initial pathogen or presumed eradication (absence of sputum for culture in a patient with a clinical response).
The bacteriologically evaluable population contained 654 patients in the CDN 200-mg group, 592 in the CDN 400-mg group, and 664 in the comparator group. A total of 1223 target pathogens were isolated before treatment: 406 isolates of S pneumoniae (including 56 penicillin-nonsusceptible [intermediate + resistant] strains), 595 isolates of H influenzae, and 222 isolates of M catarrbalis. The microbiologic response ranged from 84.1% to 88.8% in the CAP studies and from 75.1% to 77.1% in the AECB studies, with no differences between the CDN 200-mg, CDN 400-mg, and comparator groups. In the analysis of per-pathogen bacteriologic response, similar response rates were found for S pneumoniae (range, 88.5%-92.0%), H influenzae (range, 82.7%-86.6%), and M catarrbalis (range, 84.1%-95.2%), with no significant differences between groups. Focusing on penicillin-nonsusceptible (MIC >or=0.12 microg/mL) strains of S pneumoniae, CDN (both doses pooled) was associated with a response rate of 92.3% (36/39 isolates); all nonresponders were in the CDN 200-mg group. When only penicillin-resistant (MIC >or=2 microg/mL) strains were considered, there was only 1 nonresponder, again in the CDN 200-mg group. Thus, the overall response rate to CDN (both doses pooled) was 94.4% (17/18 isolates).
In this pooled analysis, CDN was associated with high rates of per-pathogen bacteriologic response among the main causative pathogens in lower respiratory tract infection. The rates of response were approximately 85% against H influenzae and approximately 90% against S pneumoniae, including penicillin-intermediate and penicillin-resistant strains.
社区获得性肺炎（CAP）和慢性支气管炎急性加重（AECB）常由肺炎链球菌、流感嗜血杆菌和卡他莫拉菌引起；因此，这些是抗生素治疗的目标病原体。
进行这项汇总分析以评估头孢妥仑匹酯（CDN）在治疗下呼吸道感染（CAP或AECB）患者中的疗效。特别关注的是最常见病原体肺炎链球菌、流感嗜血杆菌和卡他莫拉菌中每种病原体的细菌学反应率。
回顾了CDN治疗社区获得性下呼吸道感染的所有临床试验的最终报告。从4项CAP研究（3项随机研究和1项非对照研究）和3项AECB研究中汇总了CDN 200和400 mg及对照治疗的微生物学结果数据。对照药物为标准口服治疗药物，即克拉霉素500 mg每日2次、头孢呋辛250 mg每日2次、头孢泊肟酯200 mg每日2次以及阿莫西林/克拉维酸500/125 mg每日3次或875/125 mg每日2次。微生物学反应定义为初始病原体的清除或推测清除（临床有反应的患者痰培养阴性）。
细菌学可评估人群中，CDN 200 mg组有654例患者，CDN 400 mg组有592例患者，对照组有664例患者。治疗前共分离出1223株目标病原体：406株肺炎链球菌（包括56株对青霉素不敏感[中介+耐药]菌株）、595株流感嗜血杆菌和222株卡他莫拉菌。在CAP研究中，微生物学反应率为84.1%至88.8%，在AECB研究中为75.1%至77.1%，CDN 200 mg组、CDN 400 mg组和对照组之间无差异。在每种病原体细菌学反应分析中-，肺炎链球菌（范围为88.5%至92.0%）、流感嗜血杆菌（范围为82.7%至86.6%）和卡他莫拉菌（范围为84.1%至95.2%）的反应率相似，组间无显著差异。对于肺炎链球菌对青霉素不敏感（MIC≥0.12μg/mL）菌株，CDN（两剂量合并）的反应率为92.3%（36/39株）；所有无反应者均在CDN 200 mg组。仅考虑对青霉素耐药（MIC≥2μg/mL）菌株时，只有1例无反应者，同样在CDN 200 mg组。因此，CDN（两剂量合并）的总体反应率为94.4%（17/18株）。
在这项汇总分析中，CDN在治疗下呼吸道感染的主要病原体中，每种病原体的细菌学反应率较高。对流感嗜血杆菌的反应率约为85%，对肺炎链球菌（包括青霉素中介和耐药菌株）的反应率约为90%。
