Article record

日本儿童急性中耳炎致病流感嗜血杆菌的抗菌药物耐药性与分子流行病学

Antimicrobial Resistance and Molecular Epidemiology of Haemophilus influenzae Causing Pediatric Acute Otitis Media in Japan.

临床研究耳科IF 2.1Q2

文献信息

PMID	42937372
原文	在 PubMed 查看原文 ↗
发表日期	2026
作者	Shiori Kitaya 查看其他 7 位作者 Risako Kakuta；Ryuji Sakata；Miho Ogawa；Tetsuya Oishi；Tetsuji Aoyagi；Hisakazu Yano；Yukio Katori
作者单位	From the Department of Otolaryngology, Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan. 查看其他 5 条单位信息 Department of Infectious Diseases and Laboratory Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.；Department of Bacteriology, BML Inc., Kawagoe, Saitama, Japan.；Department of Clinical Infectious Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan.；Department of Clinical Microbiology and Infection, Tohoku University Graduate School of Medicine, Sendai, Japan.；Department of Microbiology and Infectious Diseases, Nara Medical University, Kashihara, Nara, Japan.
期刊	The Pediatric infectious disease journal
SCI 分区	Q2
IF	2.1
研究类型	临床研究 · 临床
所属专科	耳科

中文摘要

背景： 耐药流感嗜血杆菌菌株与急性中耳炎（AOM）的治疗失败和复发相关。本研究旨在描述当前儿童AOM分离流感嗜血杆菌的抗菌药物敏感性特征，阐明β-内酰胺类和喹诺酮类耐药机制，并确定耐药菌株的分子流行病学。
方法： 我们分析了2022年2月至2023年5月期间来自日本多个地区年龄≤3岁AOM患儿中耳液的182株流感嗜血杆菌分离株。进行了抗菌药物敏感性检测，并检测了β-内酰胺酶基因（blaTEM-1和blaROB-1）。对编码PBP3的ftsI及喹诺酮耐药决定区进行序列分析，以阐明耐药机制。对氨苄西林和喹诺酮低敏感菌株进行了多位点序列分型（MLST）。
结果： 在182株分离株中，产β-内酰胺酶、不产β-内酰胺酶氨苄西林耐药（BLNAR）、低度BLNAR和不产β-内酰胺酶氨苄西林敏感菌株分别为14株（7.7%）、10株（5.5%）、36株（19.8%）和122株（67.0%）。全部10株BLNAR和4株产β-内酰胺酶分离株均表现出与高水平耐药相关的Ⅲ组PBP3氨基酸替换。MLST显示BLNAR分离株存在遗传多样性，而7株（50.0%）产β-内酰胺酶分离株属于ST103，提示克隆传播。在6株喹诺酮低敏感菌株中检测到喹诺酮耐药决定区的氨基酸替换；这些分离株表现出多样的ST型。
结论： 引起儿童AOM的流感嗜血杆菌分离株对β-内酰胺类的敏感性总体改善。然而，观察到喹诺酮低敏感菌株呈增加趋势。在一些产β-内酰胺酶菌株中检测到以ST103为代表的特定克隆，值得仔细监测。

英文摘要

BACKGROUND: Antimicrobial-resistant strains of Haemophilus influenzae are associated with treatment failure and recurrence in acute otitis media (AOM). We aimed to characterize the current antimicrobial susceptibility of H. influenzae isolates from children with AOM, elucidate β-lactam and quinolone resistance mechanisms, and determine the molecular epidemiology of resistant strains.
METHODS: We analyzed 182 H. influenzae isolates from the middle ear fluid of children aged ≤3 years with AOM from multiple regions in Japan (February 2022-May 2023). Antimicrobial susceptibility was tested, and β-lactamase genes (blaTEM-1 and blaROB-1) were detected. Sequence analyses of ftsI, encoding PBP3 and quinolone resistance-determining regions were performed to elucidate the resistance mechanisms. Multilocus sequence typing (MLST) was conducted for the ampicillin- and quinolone-low-susceptible strains.
RESULTS: Of 182 isolates, 14 (7.7%), 10 (5.5%), 36 (19.8%) and 122 (67.0%) were β-lactamase-producing, β-lactamase-nonproducing ampicillin-resistant (BLNAR), low-BLNAR and β-lactamase-nonproducing ampicillin-susceptible strains, respectively. All 10 BLNAR and 4 β-lactamase-producing isolates exhibited group III PBP3 amino acid substitutions associated with high-level resistance. MLST revealed genetic diversity among BLNAR isolates, whereas 7 (50.0%) β-lactamase-producing isolates belonged to ST103, indicating clonal dissemination. Amino acid substitutions in the quinolone resistance-determining region were detected in six quinolone-low-susceptible strains; these isolates exhibited diverse STs.
CONCLUSIONS: The β-lactam susceptibility of H. influenzae isolates causing pediatric AOM exhibited an overall improvement. However, an increasing trend in quinolone-low-susceptible strains was observed. Specific clones represented by ST103 were detected among some of the β-lactamase-producing strains, warranting careful monitoring.