Department of Epidemiology and Social Medicine, Faculty of Medicine and Health sciences, University of Antwerp, Antwerp, Belgium.
Mycobacteriology Research Center, Jimma University, Jimma, Ethiopia.
Microbiol Spectr. 2024 Feb 6;12(2):e0293123. doi: 10.1128/spectrum.02931-23. Epub 2024 Jan 8.
In patients with presumptive tuberculosis (TB) in whom the diagnosis of TB was excluded, understanding the bacterial etiology of lower respiratory tract infections (LRTIs) is important for optimal patient management. A secondary analysis was performed on a cohort of 250 hospitalized patients with symptoms of TB. Bacterial DNA was extracted from sputum samples for Illumina 16S rRNA sequencing to identify bacterial species based on amplicon sequence variant level. The bacterial pathogen most likely to be responsible for the patients' LRTI could only be identified in a minority (6.0%, 13/215) of cases based on 16S rRNA amplicon sequencing: ( = 7), ( = 2), ( = 2), and ( = 2). Other putative pathogens were present in similar proportions of Xpert Ultra-positive and Xpert Ultra-negative sputum samples. The presence of () appeared to increase the odds of radiological abnormalities (aOR 2.5, 95% CI 1.12-6.16) and the presence of () (aOR 5.31, 95% CI 1.29-26.6) and (aOR 12.1, 95% CI 2.67-72.8) increased the odds of 6-month mortality, suggesting that these pathogens might have clinical relevance. , and appeared to be the possible causes of TB-like symptoms. () and / also appeared of clinical relevance based on 16S rRNA amplicon sequencing. Further research using tools with higher discriminatory power than 16S rRNA sequencing is required to develop optimal diagnostic and treatment strategies for this population.IMPORTANCEThe objective of this study was to identify possible bacterial lower respiratory tract infection (LRTI) pathogens in hospitalized patients who were initially suspected to have TB but later tested negative using the Xpert Ultra test. Although 16S rRNA was able to identify some less common or difficult-to-culture pathogens such as and , one of the main findings of the study is that, in contrast to what we had hypothesized, 16S rRNA is not a method that can be used to assist in the management of patients with presumptive TB having a negative Xpert Ultra test. Even though this could be considered a negative finding, we believe it is an important finding to report as it highlights the need for further research using different approaches.
在被怀疑患有结核病（TB）但最终排除 TB 诊断的患者中，了解下呼吸道感染（LRTIs）的细菌病因对于优化患者管理非常重要。对 250 名有 TB 症状的住院患者进行了队列的二次分析。从痰样本中提取细菌 DNA，进行 Illumina 16S rRNA 测序，根据扩增子序列变异水平鉴定细菌种类。基于 16S rRNA 扩增子测序，仅能在少数（6.0%，13/215）病例中确定最有可能导致患者 LRTI 的细菌病原体： （=7）、 （=2）、 （=2）和 （=2）。其他假定的病原体在 Xpert Ultra 阳性和 Xpert Ultra 阴性痰样本中存在的比例相似。 的存在似乎增加了影像学异常的几率（OR2.5，95%CI1.12-6.16）， 的存在（OR5.31，95%CI1.29-26.6）和 （OR12.1，95%CI2.67-72.8）增加了 6 个月死亡率的几率，表明这些病原体可能具有临床相关性。 、 和 似乎是引起类似 TB 症状的可能原因。 和 / 基于 16S rRNA 扩增子测序也具有临床相关性。需要使用比 16S rRNA 测序具有更高鉴别力的工具进行进一步研究，以为该人群制定最佳的诊断和治疗策略。
重要性本研究的目的是确定最初怀疑患有结核病但随后使用 Xpert Ultra 测试检测为阴性的住院患者中可能的细菌性下呼吸道感染（LRTI）病原体。尽管 16S rRNA 能够识别一些较不常见或难以培养的病原体，如 和 ，但该研究的主要发现之一是，与我们的假设相反，16S rRNA 不是一种可用于协助管理 Xpert Ultra 测试阴性的疑似 TB 患者的方法。尽管这可以被认为是一个负面发现，但我们认为这是一个重要的发现，需要报告，因为它突出了需要使用不同方法进行进一步研究。
