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日本儿童接种 13 价肺炎球菌结合疫苗后急性中耳炎的病因学和肺炎球菌分离株的特征。

Etiology of Acute Otitis Media and Characterization of Pneumococcal Isolates After Introduction of 13-Valent Pneumococcal Conjugate Vaccine in Japanese Children.

机构信息

From the Department of Infectious Diseases, Keio University, School of Medicine.

Department of Otorhinolaryngology, Hakujikai Memorial Hospital.

出版信息

Pediatr Infect Dis J. 2018 Jun;37(6):598-604. doi: 10.1097/INF.0000000000001956.

DOI:10.1097/INF.0000000000001956
PMID:29474258
Abstract

BACKGROUND

Acute otitis media is a leading cause of childhood morbidity and antibiotic prescriptions. We examined etiologic changes in acute otitis media after introduction of 13-valent pneumococcal conjugate vaccine as routine immunization for Japanese children in 2014. Serotypes, resistance genotypes, antibiotic susceptibilities and multilocus sequence typing of pneumococcal isolates were also characterized.

METHODS

Otolaryngologists prospectively collected middle ear fluid from 582 children by tympanocentesis or sampling through a spontaneously ruptured tympanic membrane between June 2016 and January 2017. Causative pathogens were identified by bacterial culture and real-time polymerase chain reaction for bacteria. Serotypes, resistance genotypes, sequence types and susceptibilities to 14 antimicrobial agents were determined for pneumococcal isolates.

RESULTS

At least 1 bacterial pathogen was identified in 473 of the samples (81.3%). Nontypeable Haemophilus influenzae (54.8%) was detected most frequently, followed by Streptococcus pneumoniae (25.4%), Streptococcus pyogenes (2.9%) and others. Pneumococci of current vaccine serotypes have decreased dramatically from 82.1% in 2006 to 18.5% (P < 0.001). Commonest serotypes were 15A (14.8%), 3 (13.9%) and 35B (11.1%). Serotype 3 was significantly less frequent among children receiving 13-valent pneumococcal conjugate vaccine compared with 7-valent pneumococcal conjugate vaccine (P = 0.002). Genotypic penicillin-resistant S. pneumoniae accounted for 28.7%, slightly less than in 2006 (34.2%; P = 0.393); the penicillin-resistant serotypes 15A and 35B had increased. Serotypes 15A, 3 and 35B most often belonged to sequence types 63, 180 and 558.

CONCLUSIONS

Our findings are expected to assist in development of future vaccines, and they underscore the need for appropriate clinical choice of oral agents based on testing of causative pathogens.

摘要

背景

急性中耳炎是儿童发病和抗生素处方的主要原因。我们研究了 2014 年日本儿童常规接种 13 价肺炎球菌结合疫苗后急性中耳炎的病因变化。还对肺炎球菌分离株的血清型、耐药基因型、抗生素敏感性和多位点序列分型进行了特征分析。

方法

耳鼻喉科医生通过鼓膜穿刺术或通过自然破裂的鼓膜采集 582 名儿童的中耳液,时间为 2016 年 6 月至 2017 年 1 月。通过细菌培养和实时聚合酶链反应对细菌进行鉴定。确定肺炎球菌分离株的血清型、耐药基因型、序列类型和对 14 种抗菌药物的敏感性。

结果

在 473 份样本(81.3%)中至少鉴定出 1 种细菌病原体。最常见的是未分型流感嗜血杆菌(54.8%),其次是肺炎链球菌(25.4%)、化脓性链球菌(2.9%)和其他病原体。当前疫苗血清型的肺炎球菌从 2006 年的 82.1%急剧下降至 18.5%(P < 0.001)。最常见的血清型是 15A(14.8%)、3 型(13.9%)和 35B(11.1%)。与 7 价肺炎球菌结合疫苗相比,接受 13 价肺炎球菌结合疫苗的儿童中 3 型明显较少(P = 0.002)。基因型青霉素耐药肺炎链球菌占 28.7%,略低于 2006 年(34.2%;P = 0.393);青霉素耐药血清型 15A 和 35B 有所增加。血清型 15A、3 和 35B 最常属于序列类型 63、180 和 558。

结论

我们的发现有望有助于未来疫苗的开发,并强调需要根据病原体检测结果,对口服药物进行适当的临床选择。

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