Abstract
Streptococcus pneumoniae is the most common cause of community-acquired pneumonia (CAP). Despite the low prevalence of CAP caused by methicillin-resistant Staphylococcus aureus (MRSA), CAP patients often receive empirical antibiotic therapy providing coverage for MRSA such as vancomycin or linezolid. An early differentiation between S. pneumoniae and S. aureus 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 S. pneumoniae and S. aureus lung infection identified an interferon signature specifically associated with S. pneumoniae 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 S. pneumoniae and S. aureus 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.
Highlights
Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality in both industrialized and developing countries [1]
We performed a genome-wide transcriptional analysis of lung tissue and blood samples of mice with S. aureus or S. pneumoniae respiratory infection and identified a robust interferon signature consistently associated with pneumococcal pneumonia that was absent in S. aureus-infected mice
This interferon signature was manifested by a marked induction of the genes encoding interferons such as IFN-β, IFN-γ, and the interferon-induced mediators such as CXCL9 and CXCL10 in lung tissue and blood cells as well as at the protein level in peripheral blood
Summary
Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality in both industrialized and developing countries [1]. Establishing a microbial diagnosis for patients with pneumonia is still challenging and, despite the rapid development of molecular diagnostic techniques, the causative agent remains unidentified in approximately 50% of CAP patients [4]. Several studies have reported the occurrence of very severe CAP cases caused by methicillin-resistant Staphylococcus aureus (MRSA) [8,9,10]. Because the clinical symptoms of S. pneumoniae and S. aureus CAP are similar if not identical [11, 12], empiric treatment regimens providing coverage for MRSA such as vancomycin or linezolid are frequently used for CAP patients until a microbiological diagnosis
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