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2018 ; 9
(ä): 1424
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An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia
#MMPMID29988532
Strehlitz A
; Goldmann O
; Pils MC
; Pessler F
; Medina E
Front Immunol
2018[]; 9
(ä): 1424
PMID29988532
show ga
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.