An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia

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...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Anja Strehlitz [verfasserIn] Oliver Goldmann [verfasserIn] Marina C. Pils [verfasserIn] Frank Pessler [verfasserIn] Eva Medina [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	pneumonia Streptococcus pneumoniae Staphylococcus aureus biomarkers interferon transcriptome

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 9(2018)
Übergeordnetes Werk:	volume:9 ; year:2018

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2018.01424

Katalog-ID:	DOAJ032780079

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520			\|a 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.
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allfields	10.3389/fimmu.2018.01424 doi (DE-627)DOAJ032780079 (DE-599)DOAJ8c4607c3c41544149bf33f564ef9807f DE-627 ger DE-627 rakwb eng RC581-607 Anja Strehlitz verfasserin aut An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. pneumonia Streptococcus pneumoniae Staphylococcus aureus biomarkers interferon transcriptome Immunologic diseases. Allergy Oliver Goldmann verfasserin aut Marina C. Pils verfasserin aut Frank Pessler verfasserin aut Eva Medina verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 9(2018) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:9 year:2018 https://doi.org/10.3389/fimmu.2018.01424 kostenfrei https://doaj.org/article/8c4607c3c41544149bf33f564ef9807f kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2018.01424/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
spelling	10.3389/fimmu.2018.01424 doi (DE-627)DOAJ032780079 (DE-599)DOAJ8c4607c3c41544149bf33f564ef9807f DE-627 ger DE-627 rakwb eng RC581-607 Anja Strehlitz verfasserin aut An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. pneumonia Streptococcus pneumoniae Staphylococcus aureus biomarkers interferon transcriptome Immunologic diseases. Allergy Oliver Goldmann verfasserin aut Marina C. Pils verfasserin aut Frank Pessler verfasserin aut Eva Medina verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 9(2018) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:9 year:2018 https://doi.org/10.3389/fimmu.2018.01424 kostenfrei https://doaj.org/article/8c4607c3c41544149bf33f564ef9807f kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2018.01424/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
allfields_unstemmed	10.3389/fimmu.2018.01424 doi (DE-627)DOAJ032780079 (DE-599)DOAJ8c4607c3c41544149bf33f564ef9807f DE-627 ger DE-627 rakwb eng RC581-607 Anja Strehlitz verfasserin aut An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. pneumonia Streptococcus pneumoniae Staphylococcus aureus biomarkers interferon transcriptome Immunologic diseases. Allergy Oliver Goldmann verfasserin aut Marina C. Pils verfasserin aut Frank Pessler verfasserin aut Eva Medina verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 9(2018) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:9 year:2018 https://doi.org/10.3389/fimmu.2018.01424 kostenfrei https://doaj.org/article/8c4607c3c41544149bf33f564ef9807f kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2018.01424/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
allfieldsGer	10.3389/fimmu.2018.01424 doi (DE-627)DOAJ032780079 (DE-599)DOAJ8c4607c3c41544149bf33f564ef9807f DE-627 ger DE-627 rakwb eng RC581-607 Anja Strehlitz verfasserin aut An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. pneumonia Streptococcus pneumoniae Staphylococcus aureus biomarkers interferon transcriptome Immunologic diseases. Allergy Oliver Goldmann verfasserin aut Marina C. Pils verfasserin aut Frank Pessler verfasserin aut Eva Medina verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 9(2018) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:9 year:2018 https://doi.org/10.3389/fimmu.2018.01424 kostenfrei https://doaj.org/article/8c4607c3c41544149bf33f564ef9807f kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2018.01424/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
allfieldsSound	10.3389/fimmu.2018.01424 doi (DE-627)DOAJ032780079 (DE-599)DOAJ8c4607c3c41544149bf33f564ef9807f DE-627 ger DE-627 rakwb eng RC581-607 Anja Strehlitz verfasserin aut An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. pneumonia Streptococcus pneumoniae Staphylococcus aureus biomarkers interferon transcriptome Immunologic diseases. Allergy Oliver Goldmann verfasserin aut Marina C. Pils verfasserin aut Frank Pessler verfasserin aut Eva Medina verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 9(2018) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:9 year:2018 https://doi.org/10.3389/fimmu.2018.01424 kostenfrei https://doaj.org/article/8c4607c3c41544149bf33f564ef9807f kostenfrei https://www.frontiersin.org/article/10.3389/fimmu.2018.01424/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
language	English
source	In Frontiers in Immunology 9(2018) volume:9 year:2018
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topic_facet	pneumonia Streptococcus pneumoniae Staphylococcus aureus biomarkers interferon transcriptome Immunologic diseases. Allergy
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container_title	Frontiers in Immunology
authorswithroles_txt_mv	Anja Strehlitz @@aut@@ Oliver Goldmann @@aut@@ Marina C. Pils @@aut@@ Frank Pessler @@aut@@ Eva Medina @@aut@@
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callnumber-first	R - Medicine
author	Anja Strehlitz
spellingShingle	Anja Strehlitz misc RC581-607 misc pneumonia misc Streptococcus pneumoniae misc Staphylococcus aureus misc biomarkers misc interferon misc transcriptome misc Immunologic diseases. Allergy An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia
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topic_title	RC581-607 An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia pneumonia Streptococcus pneumoniae Staphylococcus aureus biomarkers interferon transcriptome
topic	misc RC581-607 misc pneumonia misc Streptococcus pneumoniae misc Staphylococcus aureus misc biomarkers misc interferon misc transcriptome misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc pneumonia misc Streptococcus pneumoniae misc Staphylococcus aureus misc biomarkers misc interferon misc transcriptome misc Immunologic diseases. Allergy
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title	An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia
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title_full	An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia
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title_sort	interferon signature discriminates pneumococcal from staphylococcal pneumonia
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title_auth	An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia
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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia
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