The Impact of Next-Generation Sequencing Added to Multiplex PCR on Antibiotic Stewardship in Critically Ill Patients with Suspected Pneumonia

Kendall Kling; Chao Qi; Richard G. Wunderink; Chiagozie Pickens

doi:10.3390/diagnostics14131388

The Impact of Next-Generation Sequencing Added to Multiplex PCR on Antibiotic Stewardship in Critically Ill Patients with Suspected Pneumonia

Kendall Kling, Chao Qi, Richard G. Wunderink, Chiagozie Pickens^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Introduction: In patients with suspected pneumonia who are tested with respiratory culture and multiplex PCR, the potential added benefit of next-generation sequencing technologies is unknown. Methods: This was a single-center, retrospective study in which residual bronchoalveolar lavage (BAL) specimens were retrieved from hospitalized patients. We compared its research-use-only Respiratory Pathogen Illumina Panel (RPIP) results to culture and BioFire^® FilmArray Pneumonia Panel (BioFire^® PN) results from critically ill patients. Results: In total, 47 BAL specimens from 47 unique patients were included. All BAL samples were tested with culture and multiplex PCR. In total, 38 of the 47 BALs were consistent with a clinical picture of pneumonia per chart review. Additional testing of the 38 samples with the RPIP identified a new bacterium in 20 patients, a new virus in 4 patients, a new bacterium plus virus in 4 patients, and no additional organisms in 10 patients. In 17 (44.5%) of these patients, the RPIP results could have indicated an antibiotic addition. Compared with cultures, the RPIP had an overall sensitivity of 64% and specificity of 98%, with a 0% sensitivity for fungus and 14% sensitivity for mycobacteria. Compared with BioFire^® PN, the RPIP was 70% sensitive and 99% specific, with a 74% sensitivity for bacteria and 33% sensitivity for viruses. The RPIP was 29% more sensitive for HAP/VAP bacterial targets compared with CAP. Conclusions: Emerging NGS technologies such as the RPIP may have a role in identifying the etiology of pneumonia, even when patients have BAL culture and multiplex PCR results available. Similar to prior studies evaluating RPIP, our study showed this platform lacked sensitivity when compared with cultures, particularly for fungi and mycobacteria. However, the high specificity of the test can be leveraged when clinicians are seeking to rule out certain infections.

Original language	English (US)
Article number	1388
Journal	Diagnostics
Volume	14
Issue number	13
DOIs	https://doi.org/10.3390/diagnostics14131388
State	Published - Jul 2024

Funding

C.P. reports financial support from NIAID (U19AI135964), Northwestern University Clinical and Translational Sciences Institute (5KL2TR001424-09), and a Northwestern Memorial Hospital Masters in Medicine Institutional Grant. R.G.W. reports financial support from NIH awards U19AI135964, U01TR003528, P01HL154998, R01HL14988, and R01LM013337.

Keywords

antibiotics
critical care
diagnostics
molecular
pneumonia
respiratory

ASJC Scopus subject areas

Clinical Biochemistry

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10.3390/diagnostics14131388

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title = "The Impact of Next-Generation Sequencing Added to Multiplex PCR on Antibiotic Stewardship in Critically Ill Patients with Suspected Pneumonia",

abstract = "Introduction: In patients with suspected pneumonia who are tested with respiratory culture and multiplex PCR, the potential added benefit of next-generation sequencing technologies is unknown. Methods: This was a single-center, retrospective study in which residual bronchoalveolar lavage (BAL) specimens were retrieved from hospitalized patients. We compared its research-use-only Respiratory Pathogen Illumina Panel (RPIP) results to culture and BioFire{\textregistered} FilmArray Pneumonia Panel (BioFire{\textregistered} PN) results from critically ill patients. Results: In total, 47 BAL specimens from 47 unique patients were included. All BAL samples were tested with culture and multiplex PCR. In total, 38 of the 47 BALs were consistent with a clinical picture of pneumonia per chart review. Additional testing of the 38 samples with the RPIP identified a new bacterium in 20 patients, a new virus in 4 patients, a new bacterium plus virus in 4 patients, and no additional organisms in 10 patients. In 17 (44.5%) of these patients, the RPIP results could have indicated an antibiotic addition. Compared with cultures, the RPIP had an overall sensitivity of 64% and specificity of 98%, with a 0% sensitivity for fungus and 14% sensitivity for mycobacteria. Compared with BioFire{\textregistered} PN, the RPIP was 70% sensitive and 99% specific, with a 74% sensitivity for bacteria and 33% sensitivity for viruses. The RPIP was 29% more sensitive for HAP/VAP bacterial targets compared with CAP. Conclusions: Emerging NGS technologies such as the RPIP may have a role in identifying the etiology of pneumonia, even when patients have BAL culture and multiplex PCR results available. Similar to prior studies evaluating RPIP, our study showed this platform lacked sensitivity when compared with cultures, particularly for fungi and mycobacteria. However, the high specificity of the test can be leveraged when clinicians are seeking to rule out certain infections.",

keywords = "antibiotics, critical care, diagnostics, molecular, pneumonia, respiratory",

author = "Kendall Kling and Chao Qi and Wunderink, {Richard G.} and Chiagozie Pickens",

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AU - Pickens, Chiagozie

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N2 - Introduction: In patients with suspected pneumonia who are tested with respiratory culture and multiplex PCR, the potential added benefit of next-generation sequencing technologies is unknown. Methods: This was a single-center, retrospective study in which residual bronchoalveolar lavage (BAL) specimens were retrieved from hospitalized patients. We compared its research-use-only Respiratory Pathogen Illumina Panel (RPIP) results to culture and BioFire® FilmArray Pneumonia Panel (BioFire® PN) results from critically ill patients. Results: In total, 47 BAL specimens from 47 unique patients were included. All BAL samples were tested with culture and multiplex PCR. In total, 38 of the 47 BALs were consistent with a clinical picture of pneumonia per chart review. Additional testing of the 38 samples with the RPIP identified a new bacterium in 20 patients, a new virus in 4 patients, a new bacterium plus virus in 4 patients, and no additional organisms in 10 patients. In 17 (44.5%) of these patients, the RPIP results could have indicated an antibiotic addition. Compared with cultures, the RPIP had an overall sensitivity of 64% and specificity of 98%, with a 0% sensitivity for fungus and 14% sensitivity for mycobacteria. Compared with BioFire® PN, the RPIP was 70% sensitive and 99% specific, with a 74% sensitivity for bacteria and 33% sensitivity for viruses. The RPIP was 29% more sensitive for HAP/VAP bacterial targets compared with CAP. Conclusions: Emerging NGS technologies such as the RPIP may have a role in identifying the etiology of pneumonia, even when patients have BAL culture and multiplex PCR results available. Similar to prior studies evaluating RPIP, our study showed this platform lacked sensitivity when compared with cultures, particularly for fungi and mycobacteria. However, the high specificity of the test can be leveraged when clinicians are seeking to rule out certain infections.

AB - Introduction: In patients with suspected pneumonia who are tested with respiratory culture and multiplex PCR, the potential added benefit of next-generation sequencing technologies is unknown. Methods: This was a single-center, retrospective study in which residual bronchoalveolar lavage (BAL) specimens were retrieved from hospitalized patients. We compared its research-use-only Respiratory Pathogen Illumina Panel (RPIP) results to culture and BioFire® FilmArray Pneumonia Panel (BioFire® PN) results from critically ill patients. Results: In total, 47 BAL specimens from 47 unique patients were included. All BAL samples were tested with culture and multiplex PCR. In total, 38 of the 47 BALs were consistent with a clinical picture of pneumonia per chart review. Additional testing of the 38 samples with the RPIP identified a new bacterium in 20 patients, a new virus in 4 patients, a new bacterium plus virus in 4 patients, and no additional organisms in 10 patients. In 17 (44.5%) of these patients, the RPIP results could have indicated an antibiotic addition. Compared with cultures, the RPIP had an overall sensitivity of 64% and specificity of 98%, with a 0% sensitivity for fungus and 14% sensitivity for mycobacteria. Compared with BioFire® PN, the RPIP was 70% sensitive and 99% specific, with a 74% sensitivity for bacteria and 33% sensitivity for viruses. The RPIP was 29% more sensitive for HAP/VAP bacterial targets compared with CAP. Conclusions: Emerging NGS technologies such as the RPIP may have a role in identifying the etiology of pneumonia, even when patients have BAL culture and multiplex PCR results available. Similar to prior studies evaluating RPIP, our study showed this platform lacked sensitivity when compared with cultures, particularly for fungi and mycobacteria. However, the high specificity of the test can be leveraged when clinicians are seeking to rule out certain infections.

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The Impact of Next-Generation Sequencing Added to Multiplex PCR on Antibiotic Stewardship in Critically Ill Patients with Suspected Pneumonia

Abstract

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