Strehlitz Anja, Goldmann Oliver, Pils Marina C, Pessler Frank, Medina Eva
Infection Immunology Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Mouse Pathology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Front Immunol. 2018 Jun 25;9:1424. doi: 10.3389/fimmu.2018.01424. eCollection 2018.
is the most common cause of community-acquired pneumonia (CAP). Despite the low prevalence of CAP caused by methicillin-resistant (MRSA), CAP patients often receive empirical antibiotic therapy providing coverage for MRSA such as vancomycin or linezolid. An early differentiation between and pneumonia can help to reduce the use of unnecessary antibiotics. The objective of this study was to identify candidate biomarkers that can discriminate pneumococcal from staphylococcal pneumonia. A genome-wide transcriptional analysis of lung and peripheral blood performed in murine models of and lung infection identified an interferon signature specifically associated with infection. Prediction models built using a support vector machine and Monte Carlo cross-validation, identified the combination of the interferon-induced chemokines CXCL9 and CXCL10 serum concentrations as the set of biomarkers with best sensitivity, specificity, and predictive power that enabled an accurate discrimination between and pneumonia. The predictive performance of these biomarkers was further validated in an independent cohort of mice. This study highlights the potential of serum CXCL9 and CXCL10 biomarkers as an adjunctive diagnostic tool that could facilitate prompt and correct pathogen-targeted therapy in CAP patients.
是社区获得性肺炎（CAP）最常见的病因。尽管耐甲氧西林金黄色葡萄球菌（MRSA）引起的CAP患病率较低，但CAP患者常接受针对MRSA的经验性抗生素治疗，如万古霉素或利奈唑胺。早期区分肺炎链球菌肺炎和葡萄球菌肺炎有助于减少不必要的抗生素使用。本研究的目的是确定能够区分肺炎链球菌肺炎和葡萄球菌肺炎的候选生物标志物。在肺炎链球菌和葡萄球菌肺部感染的小鼠模型中对肺组织和外周血进行全基因组转录分析，确定了一种与肺炎链球菌感染特异性相关的干扰素特征。使用支持向量机和蒙特卡罗交叉验证构建的预测模型，确定干扰素诱导的趋化因子CXCL9和CXCL10血清浓度的组合为具有最佳敏感性、特异性和预测能力的生物标志物组合，能够准确区分肺炎链球菌肺炎和葡萄球菌肺炎。这些生物标志物的预测性能在另一组独立的小鼠中得到进一步验证。本研究强调了血清CXCL9和CXCL10生物标志物作为辅助诊断工具的潜力，可促进CAP患者及时、正确的针对病原体的治疗。
