Sunakawa Keisuke, Farrell David J
School of Medicine, Kitasato University, Kanagawa, Japan.
Ann Clin Microbiol Antimicrob. 2007 Aug 13;6:7. doi: 10.1186/1476-0711-6-7.
The clinical management of community-acquired respiratory tract infections (RTIs) is complicated by the increasing worldwide prevalence of antibacterial resistance, in particular, beta-lactam and macrolide resistance, among the most common causative bacterial pathogens. This study aimed to determine the mechanisms and molecular- and sero-epidemiology of antibacterial resistance among the key paediatric respiratory pathogens in Japan.
Isolates were collected at 18 centres in Japan during 2002 and 2003 from children with RTIs as part of the PROTEKT surveillance programme. A proportion of Haemophilus influenzae isolates was subjected to sequencing analysis of the ftsI gene; phylogenetic relatedness was assessed using multilocus sequence typing. Streptococcus pneumoniae isolates were screened for macrolide-resistance genotype by polymerase chain reaction and serotyped using the capsular swelling method. Susceptibility of isolates to selected antibacterials was performed using CLSI methodology.
Of the 557 H. influenzae isolates collected, 30 (5.4%) were beta-lactamase-positive [BL+], 115 (20.6%) were BL-nonproducing ampicillin-resistant (BLNAR; MIC >or= 4 mg/L) and 79 (14.2%) were BL-nonproducing ampicillin-intermediate (BLNAI; MIC 2 mg/L). Dabernat Group III penicillin binding protein 3 (PBP3) amino acid substitutions in the ftsI gene were closely correlated with BLNAR status but phylogenetic analysis indicated marked clonal diversity. PBP mutations were also found among BL+ and BL-nonproducing ampicillin-sensitive isolates. Of the antibacterials tested, azithromycin and telithromycin were the most active against H. influenzae (100% and 99.3% susceptibility, respectively). A large proportion (75.2%) of the 468 S. pneumoniae isolates exhibited macrolide resistance (erythromycin MIC >or= 1 mg/L); erm(B) was the most common macrolide resistance genotype (58.8%), followed by mef(A) (37.2%). The most common pneumococcal serotypes were 6B (19.7%), 19F (13.7%), 23F (13.5%) and 6A (12.8%). Telithromycin and amoxicillin-clavulanate were the most active antibacterials against S. pneumoniae (99.8% and 99.6% susceptibility, respectively).
Approximately one-third of H. influenzae isolates from paediatric patients in Japan are BLNAI/BLNAR, mainly as a result of clonally diverse PBP3 mutations. Together with the continued high prevalence of pneumococcal macrolide resistance, these results may have implications for the clinical management of paediatric RTIs in Japan.
全球范围内，抗菌药物耐药性，尤其是最常见致病细菌病原体中的β-内酰胺类和大环内酯类耐药性日益普遍，这使得社区获得性呼吸道感染（RTIs）的临床管理变得复杂。本研究旨在确定日本主要儿科呼吸道病原体的抗菌药物耐药机制以及分子和血清流行病学情况。
作为PROTEKT监测项目的一部分，2002年至2003年期间在日本的18个中心收集了RTIs患儿的分离株。对一部分流感嗜血杆菌分离株进行ftsI基因测序分析；使用多位点序列分型评估系统发育相关性。通过聚合酶链反应筛选肺炎链球菌分离株的大环内酯耐药基因型，并使用荚膜肿胀法进行血清分型。使用CLSI方法检测分离株对选定抗菌药物的敏感性。
在收集的557株流感嗜血杆菌分离株中，30株（5.4%）为β-内酰胺酶阳性[BL+]，115株（20.6%）为不产β-内酰胺酶的氨苄西林耐药株（BLNAR；MIC≥4mg/L），79株（14.2%）为不产β-内酰胺酶的氨苄西林中介株（BLNAI；MIC 2mg/L）。ftsI基因中达伯奈特III组青霉素结合蛋白3（PBP3）氨基酸替代与BLNAR状态密切相关，但系统发育分析表明存在明显的克隆多样性。在BL+和不产β-内酰胺酶的氨苄西林敏感分离株中也发现了PBP突变。在所测试的抗菌药物中，阿奇霉素和泰利霉素对流感嗜血杆菌的活性最高（敏感性分别为100%和99.3%）。在468株肺炎链球菌分离株中，很大一部分（75.2%）表现出大环内酯耐药性（红霉素MIC≥1mg/L）；erm(B)是最常见的大环内酯耐药基因型（58.8%），其次是mef(A)（37.2%）。最常见的肺炎球菌血清型为6B（19.7%）、19F（13.7%）、23F（13.5%）和6A（12.8%）。泰利霉素和阿莫西林-克拉维酸是对肺炎链球菌活性最高的抗菌药物（敏感性分别为99.8%和99.6%）。
日本儿科患者中约三分之一的流感嗜血杆菌分离株为BLNAI/BLNAR，主要是由于PBP3突变的克隆多样性。连同肺炎球菌大环内酯耐药性的持续高流行率，这些结果可能对日本儿科RTIs的临床管理产生影响。
