AUTHOR=Strehlitz Anja , Goldmann Oliver , Pils Marina C. , Pessler Frank , Medina Eva 

TITLE=An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01424

DOI=10.3389/fimmu.2018.01424

ISSN=1664-3224

ABSTRACT=<p><italic>Streptococcus pneumoniae</italic> is the most common cause of community-acquired pneumonia (CAP). Despite the low prevalence of CAP caused by methicillin-resistant <italic>Staphylococcus aureus</italic> (MRSA), CAP patients often receive empirical antibiotic therapy providing coverage for MRSA such as vancomycin or linezolid. An early differentiation between <italic>S. pneumoniae</italic> and <italic>S. aureus</italic> 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 <italic>S. pneumoniae</italic> and <italic>S. aureus</italic> lung infection identified an interferon signature specifically associated with <italic>S. pneumoniae</italic> 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 <italic>S. pneumoniae</italic> and <italic>S. aureus</italic> 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.</p>