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Host Transcriptional Signatures Predict Etiology in Community-Acquired Pneumonia: Potential Antibiotic Stewardship
William W Siljan1, Dhanasekaran Sivakumaran2,3, Christian Ritz2,4
1Department of Pulmonary Medicine, Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
Background:
Current approaches for pathogen identification in community-acquired pneumonia (CAP) remain suboptimal, leaving most patients without a microbiological diagnosis. If better diagnostic tools were available for differentiating between viral and bacterial CAP, unnecessary antibacterial therapy could be avoided in viral CAP patients.
Methods:
In 156 adults hospitalized with CAP classified to have bacterial, viral, or mixed viral-bacterial infection based on microbiological testing or both microbiological testing and procalcitonin (PCT) levels, we aimed to identify discriminatory host transcriptional signatures in peripheral blood samples acquired at hospital admission, by applying Dual-color-Reverse-Transcriptase-Multiplex-Ligation-dependent-Probe-Amplification (dc-RT MLPA).
Results:
In patients classified by microbiological testing, a 9-transcript signature showed high accuracy for discriminating bacterial from viral CAP (AUC 0.91, 95% CI 0.85-0.96), while a 10-transcript signature similarly discriminated mixed viral-bacterial from viral CAP (AUC 0.91, 95% CI 0.86-0.96). In patients classified by both microbiological testing and PCT levels, a 13-transcript signature showed excellent accuracy for discriminating bacterial from viral CAP (AUC 1.00, 95% CI 1.00-1.00), while a 7-transcript signature similarly discriminated mixed viral-bacterial from viral CAP (AUC 0.93, 95% CI 0.87-0.98).
Conclusion:
Our findings support host transcriptional signatures in peripheral blood samples as a potential tool for guiding clinical decision-making and antibiotic stewardship in CAP.
Insights
Accurate pathogen identification in community-acquired pneumonia (CAP) is crucial. Host transcriptional signatures in blood show promise for differentiating bacterial from viral CAP, aiding antibiotic stewardship.
Area of Science:
- Medical diagnostics
- Molecular biology
- Infectious disease
Background:
- Current methods for identifying pathogens in community-acquired pneumonia (CAP) are insufficient, leading to a lack of diagnosis for most patients.
- Improved diagnostic tools are needed to distinguish between viral and bacterial CAP, thereby reducing unnecessary antibiotic use in viral cases.
Purpose of the Study:
- To identify host transcriptional signatures in peripheral blood that can differentiate between bacterial, viral, and mixed viral-bacterial infections in hospitalized CAP patients.
- To evaluate the diagnostic accuracy of these signatures using Dual-color-Reverse-Transcriptase-Multiplex-Ligation-dependent-Probe-Amplification (dc-RT MLPA).
Main Methods:
- 156 adult CAP patients were analyzed.
- Peripheral blood samples were collected at hospital admission.
- Dual-color-Reverse-Transcriptase-Multiplex-Ligation-dependent-Probe-Amplification (dc-RT MLPA) was used to identify host transcriptional signatures.
Main Results:
- A 9-transcript signature accurately discriminated bacterial from viral CAP (AUC 0.91) when patients were classified by microbiological testing.
- A 13-transcript signature showed perfect accuracy (AUC 1.00) in discriminating bacterial from viral CAP when patients were classified by microbiological testing and procalcitonin (PCT) levels.
- Signatures also effectively differentiated mixed viral-bacterial from viral CAP.
Conclusions:
- Host transcriptional signatures in peripheral blood are a promising tool for diagnosing CAP etiology.
- These signatures can guide clinical decisions and support antibiotic stewardship efforts in managing CAP.
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