目的 探讨靶向二代测序（targeted next-generation sequencing, tNGS）对中重度呼吸窘迫综合征（respiratory distress syndrome, RDS）新生儿病原学诊断的应用价值。 方法 采用前瞻性随机对照研究，纳入2023年12月—2024年12月福建省儿童医院收治的81例足月或近足月中重度RDS患儿，随机分为常规微生物检测（conventional microbiological test, CMT）组（n=42）和tNGS组（n=39）。CMT组经支气管镜获取支气管肺泡灌洗液或气管插管获取下呼吸道样本进行常规病原学检测（所有均送培养，部分加做聚合酶链反应或抗原检测），tNGS组在常规病原学检测的基础上联合tNGS技术进行病原体分析。对两组病原体检出率、混合感染检出率及抗菌药物使用时间等指标进行比较。 结果 tNGS组病原体检出率（18/39）显著高于CMT组（8/42）（46% vs 19%，P=0.009），其中混合感染检出率为13%（5/39），而CMT组未检出混合感染（P=0.024）。在治疗方面，tNGS组抗菌药物使用时间短于CMT组［（12±4）d vs（15±5）d，P=0.003］。 结论 tNGS能显著提高中重度RDS新生儿的病原体检出效率，具有快速识别混合感染及缩短抗菌药物疗程的优势，有临床推广价值。

Objective To investigate the application value of targeted next-generation sequencing (tNGS) in the etiological diagnosis of moderate to severe respiratory distress syndrome (RDS) in neonates. Methods A prospective randomized controlled trial was conducted, enrolling 81 term and late-preterm neonates with moderate to severe RDS admitted to Fujian Children's Hospital between December 2023 and December 2024. Patients were randomly assigned to the conventional microbiological test (CMT) group (n=42) or the tNGS group (n=39). For routine pathogen detection, bronchoalveolar lavage fluid was obtained via bronchoscopy, and lower respiratory tract specimens were collected via the endotracheal tube; all specimens underwent culture, and some specimens additionally underwent polymerase chain reaction or antigen testing. In the tNGS group, tNGS was performed in addition to routine pathogen detection on the same specimen types. The detection rate of pathogens, the detection rate of co-infections, and the duration of antibiotic use were compared between the two groups. Results The pathogen detection rate in the tNGS group (18/39, 46%) was significantly higher than that in the CMT group (8/42, 19%) (P=0.009). The co-infection detection rate was 13% (5/39) in the tNGS group, while no co-infections were identified in the CMT group (P=0.024). Regarding treatment, the duration of antibiotic use in the tNGS group was shorter than that in the CMT group [(12±4) days vs (15±5) days, P=0.003]. Conclusions tNGS significantly improves the pathogen detection rate in neonates with moderate to severe RDS and offers advantages in the rapid identification of co-infections and reduction of antibiotic treatment duration, suggesting it has clinical utility and potential for wider adoption.