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中国山东西南部儿童卡他莫拉菌引起的下呼吸道感染的致病性及Bro基因分型

Pathogenicity and Bro gene typing of pediatric lower respiratory tract infections with Moraxella catarrhalis in Southwest Shandong, China.

作者信息

Xiang Yuhan, Shi Jian, Han Liang, Yang Chengfan, Lu Shuhua

机构信息

Clinical Laboratory, Affiliated Hospital of Jining Medical University, No. 89, Guhuai Road, Jining, 272000, Shandong, China.

Clinical Medicine, Jining Medical University, Jining, China.

出版信息

Sci Rep. 2025 Apr 29;15(1):15070. doi: 10.1038/s41598-025-99873-1.

Abstract

To investigate the etiology and clinical characteristics of Moraxella catarrhalis infections in the lower respiratory tract among pediatric patients in southwestern Shandong Province, China. This study aims to enhance early identification and diagnostic accuracy for laboratory physicians, while providing evidence to guide clinical diagnosis and treatment of Moraxella catarrhalis-related infections. This retrospective cohort study analyzed pediatric patients with Moraxella catarrhalis lower respiratory tract infections in southwestern Shandong Province, China. Clinical isolates were obtained through standardized sputum/bronchoalveolar lavage collection protocols and subjected to microbiological identification, antimicrobial susceptibility testing, and molecular characterization of β-lactamase production and bro gene variants. Epidemiological patterns and clinical profiles were systematically evaluated using electronic medical record data spanning January 2020 to December 2023. During the 4-year surveillance period (2018-2021), Moraxella catarrhalis was isolated from 848 pediatric cases of lower respiratory tract infections, representing a 7.81% overall detection rate. Age-stratified analysis revealed the highest prevalence in infants aged 28 days to 1 year (9.69%), with significant seasonal variation peaking in the fourth quarter (11.58%, p < 0.05). Monomicrobial infections predominated (79.72%, 676/848), while polymicrobial cases (20.28%, 172/848) predominantly co-occurred with Streptococcus pneumoniae and Haemophilus influenzae. All isolates were confirmed through parallel testing using automated biochemical analyzers and MALDI-TOF mass spectrometry. Antimicrobial susceptibility profiling demonstrated complete susceptibility to ceftazidime, cefepime, and imipenem (100%), with ≥ 95% susceptibility rates to ciprofloxacin (98.2%), levofloxacin (97.6%), ceftriaxone (96.8%), cefuroxime (96.1%), tetracycline (95.4%), and chloramphenicol (95.1%). A concerning temporal escalation in erythromycin resistance was observed (69.73% in 2018 vs. 90.57% in 2021, χ²=41.32, p < 0.001), while ampicillin and clindamycin resistance remained persistently high (> 93% across all years).β-lactamase production was detected in 96.58% (819/848) of isolates, with molecular characterization identifying bro-1 (94.51%, 774/819) and bro-2 (5.49%, 45/819) gene variants. The β-lactamase-negative subgroup (3.42%, 29/848) showed no significant epidemiological clustering. Our surveillance study demonstrates that Moraxella catarrhalis lower respiratory tract infections in southwestern Shandong Province predominantly affect infants aged 28 days to 1 year, with significantly elevated seasonal incidence during the fourth quarter. Notably, we observed a concerning temporal escalation in erythromycin resistance and persistently high resistance rates to ampicillinand clindamycin throughout the 2018-2021 surveillance period. Crucially, β-lactamase hyperproduction particularly BRO-1 gene carriage emerged as the principal resistance mechanism against β-lactams, while maintained susceptibility to expanded-spectrum cephalosporins and carbapenems suggests preserved therapeutic options. These findings underscore the necessity for: Avoidance of macrolides and β-lactam/β-lactamase inhibitor combinations in empirical therapy; Continuous monitoring of BRO gene evolution patterns; Age-specific antimicrobial stewardship programs targeting infant populations.

摘要

为调查中国山东省西南部儿科患者下呼吸道卡他莫拉菌感染的病因及临床特征。本研究旨在提高实验室医生的早期识别能力和诊断准确性,同时为指导卡他莫拉菌相关感染的临床诊断和治疗提供依据。这项回顾性队列研究分析了中国山东省西南部患有卡他莫拉菌下呼吸道感染的儿科患者。通过标准化的痰液/支气管肺泡灌洗采集方案获得临床分离株,并进行微生物鉴定、抗菌药物敏感性测试以及β-内酰胺酶产生和bro基因变异的分子特征分析。利用2020年1月至2023年12月的电子病历数据系统评估流行病学模式和临床特征。在4年监测期(2018 - 2021年)内,从848例儿科下呼吸道感染病例中分离出卡他莫拉菌,总体检出率为7.81%。年龄分层分析显示,28天至1岁婴儿的患病率最高(9.69%),有显著的季节性变化,第四季度达到高峰(11.58%,p < 0.05)。单一微生物感染占主导(79.72%,676/848),而多重微生物感染病例(20.28%,172/848)主要与肺炎链球菌和流感嗜血杆菌同时出现。所有分离株均通过使用自动生化分析仪和基质辅助激光解吸电离飞行时间质谱进行平行检测得到确认。抗菌药物敏感性分析表明,对头孢他啶、头孢吡肟和亚胺培南完全敏感(100%),对环丙沙星(98.2%)、左氧氟沙星(97.6%)、头孢曲松(96.8%)、头孢呋辛(96.1%)、四环素(95.4%)和氯霉素(95.1%)的敏感率≥95%。观察到红霉素耐药性随时间呈令人担忧的上升趋势(2018年为69.73%,2021年为90.57%,χ²=41.32,p < 0.001),而氨苄西林和克林霉素耐药率一直居高不下(各年份均>93%)。在848株分离株中,96.58%(819/848)检测到β-内酰胺酶产生,分子特征鉴定出bro-1(94.51%,774/819)和bro-2(5.49%,45/819)基因变异。β-内酰胺酶阴性亚组(3.42%,29/848)未显示出明显的流行病学聚集性。我们的监测研究表明,中国山东省西南部卡他莫拉菌下呼吸道感染主要影响28天至1岁的婴儿,第四季度季节性发病率显著升高。值得注意的是,在2018 - 2021年监测期内,我们观察到红霉素耐药性随时间呈令人担忧的上升趋势,氨苄西林和克林霉素耐药率一直居高不下。至关重要的是,β-内酰胺酶过度产生,尤其是BRO-1基因携带,成为对β-内酰胺类药物的主要耐药机制,而对广谱头孢菌素和碳青霉烯类药物保持敏感表明仍有可用的治疗选择。这些发现强调了以下必要性:在经验性治疗中避免使用大环内酯类药物以及β-内酰胺/β-内酰胺酶抑制剂组合;持续监测BRO基因的进化模式;针对婴儿群体制定特定年龄的抗菌药物管理计划。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b010/12041543/217aaed9fbdf/41598_2025_99873_Fig1_HTML.jpg

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