State Key Laboratory of Organ Failure Research, Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Pharmacol Res. 2020 Oct;160:105095. doi: 10.1016/j.phrs.2020.105095. Epub 2020 Jul 28.
Identification of risk factors for antibiotic treatment failure is urgently needed in acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Here we investigated the relationship between sputum microbiome and clinical outcome of choice of initial antibiotics during hospitalization of AECOPD patients. Sputum samples of 41 AECOPD patients and 26 healthy controls were collected from Guangzhou Medical University, China. Samples were processed for 16S rRNA gene-based microbiome profiling. Thirty patients recovered with initial antibiotic treatment (antibiotic success or AS), while 11 patients showed poor outcome (antibiotic failure or AF). Substantial differences in microbiome were observed in AF versus AS patients and healthy controls. There was significantly decreased alpha diversity and increased relative abundances of Pseudomonas, Achromobacter, Stenotrophomonas and Ralstonia in AF patients. Conversely, Prevotella, Peptostreptococcus, Leptotrichia and Selenomonas were depleted. The prevalence of Selenomonas was markedly reduced in AF versus AS patients (9.1 % versus 60.0 %, P = 0.004). The AF patients with similar microbiome profiles in general responded well to the same new antibiotics in the adjusted therapy, indicating sputum microbiome may help guide the adjustment of antibiotics. Random forest analysis identified five microbiome operational taxonomic units together with C-reactive protein, procalcitonin and blood neutrophil count showing best predictability for antibiotic treatment outcome (area under curve 0.885). Functional inference revealed an enrichment of microbial genes in xenobiotic metabolism and antimicrobial resistance in AF patients, whereas genes in DNA repair and amino acid metabolism were depleted. Sputum microbiome may determine the clinical outcome of initial antibiotic treatment and be considered in the risk management of antibiotics in AECOPD.
在慢性阻塞性肺疾病（COPD）急性加重期（AECOPD）中，迫切需要确定抗生素治疗失败的风险因素。在这里，我们研究了痰液微生物组与 AECOPD 患者住院期间初始抗生素选择的临床结果之间的关系。从中国广州医科大学收集了 41 名 AECOPD 患者和 26 名健康对照者的痰液样本。对样本进行了基于 16S rRNA 基因的微生物组分析。30 名患者经初始抗生素治疗后康复（抗生素成功或 AS），而 11 名患者的治疗结果不佳（抗生素失败或 AF）。在 AF 患者与 AS 患者和健康对照者之间观察到微生物组存在显著差异。AF 患者的 alpha 多样性显著降低，假单胞菌、不动杆菌、嗜麦芽窄食单胞菌和罗尔斯通氏菌的相对丰度增加。相反，普雷沃氏菌、消化链球菌、脱硫弧菌和唾液链球菌减少。与 AS 患者相比，AF 患者中唾液链球菌的患病率显著降低（9.1%比 60.0%，P=0.004）。具有相似微生物组谱的 AF 患者在调整后的治疗中通常对相同的新抗生素反应良好，这表明痰液微生物组可能有助于指导抗生素的调整。随机森林分析确定了五个微生物组操作分类单元，以及 C 反应蛋白、降钙素原和血液中性粒细胞计数，这些单元对抗生素治疗结果的预测能力最佳（曲线下面积为 0.885）。功能推断显示，在 AF 患者中，微生物基因在异生物质代谢和抗微生物耐药性方面富集，而在 DNA 修复和氨基酸代谢方面则减少。痰液微生物组可能决定初始抗生素治疗的临床结果，并可在 AECOPD 中抗生素风险管理中加以考虑。
