TY - JOUR
T1 - Microbial Volatiles as Diagnostic Biomarkers of Bacterial Lung Infection in Mechanically Ventilated Patients
AU - Ahmed, Waqar M.
AU - Fenn, Dominic
AU - White, Iain R.
AU - Dixon, Breanna
AU - Nijsen, Tamara M. E.
AU - Knobel, Hugo H.
AU - Brinkman, Paul
AU - van Oort, Pouline M. P.
AU - Schultz, Marcus J.
AU - Dark, Paul
AU - Goodacre, Royston
AU - Felton, Timothy
AU - Bos, Lieuwe D. J.
AU - Fowler, Stephen J.
AU - BreathDx Consortium
AU - Ahmed, Waqar M.
AU - Raventos, Antonio Artigas
AU - Bannard-Smith, Jonathan
AU - Bos, Lieuwe D. J.
AU - Camprubi, Marta
AU - Coelho, Luis
AU - Dark, Paul
AU - Davie, Alan
AU - Diaz, Emili
AU - Goma, Gemma
AU - Felton, Timothy
AU - Fowler, Stephen J.
AU - Goodacre, Royston
AU - Johnson, Craig
AU - Knobel, Hugo
AU - Lawal, Oluwasola
AU - Leopold, Jan-Hendrik
AU - Martin-Loeches, Ignacio
AU - Nijsen, Tamara M. E.
AU - van Oort, Pouline M. P.
AU - Povoa, Pedro
AU - Rattray, Nicholas J. W.
AU - Rijnders, Guus
AU - Schultz, Marcus J.
AU - Steenwelle, Ruud
AU - Sterk, Peter J.
AU - Valles, Jordi
AU - Verhoeckx, Fred
AU - Vink, Anton
AU - Weda, Hans
AU - White, Iain R.
AU - Winters, Tineke
AU - Zakharkina, Tetyana
N1 - Funding Information: Potential conflicts of interest. P. D. is Deputy Medical Director, NIHR National Research Network (payment to institution), and NIHR Senior Investigator (payment to employing institution). B. D. reports travel accommodation from Markes International for the Breath Summit conference 2022. L. D. J. B. reports consulting fees from Scailyte and Santhera (paid to institution) and participation on advisory board for Sobi, Excastat, Pfizer, and AstraZeneca. P. B. reports grants for development of chemical sensor–driven technology from Amsterdam University Medical Center (Innovatie Impuls 2020), Vertex (Vertex Innovation Award 2022), Stichting Astma Bestrijding, and Boehringer Ingelheim; a public-private partnership grant from Eurostars; and a grant for Disaster-Resilient Society 2021 (HORIZON-CL3-2021-DRS-01) from the Horizon Europe Framework Programme. All other authors report no potential conflicts. Funding Information: Financial support . This work was supported by the FP7 People: Marie-Curie Actions, under the Industry-Academia Partnerships and Pathways (IAPP) program (MC-IAPP BreathDx 611951), and supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre and the NIHR Manchester Clinical Research Facility. I. R. W. is supported by the Slovenian Research Agency (program P1-0034: Analytics and Chemical Characterization of Materials and Processes). B. D. reports support from the Biotechnology and Biological Sciences Research Council (grant number BB/T008725/1, PhD studentship, funded to institution). Publisher Copyright: © 2022 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.
PY - 2023/3/15
Y1 - 2023/3/15
N2 - Background: Early and accurate recognition of respiratory pathogens is crucial to prevent increased risk of mortality in critically ill patients. Microbial-derived volatile organic compounds (mVOCs) in exhaled breath could be used as noninvasive biomarkers of infection to support clinical diagnosis. Methods: In this study, we investigated the diagnostic potential of in vitro-confirmed mVOCs in the exhaled breath of patients under mechanical ventilation from the BreathDx study. Samples were analyzed by thermal desorption-gas chromatography-mass spectrometry. Results: Pathogens from bronchoalveolar lavage (BAL) cultures were identified in 45 of 89 patients and Staphylococcus aureus was the most commonly identified pathogen (n = 15). Of 19 mVOCs detected in the in vitro culture headspace of 4 common respiratory pathogens (S. aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli), 14 were found in exhaled breath samples. Higher concentrations of 2 mVOCs were found in the exhaled breath of patients infected with S. aureus compared to those without (3-methylbutanal: P <. 01, area under the receiver operating characteristic curve [AUROC] = 0.81-0.87; and 3-methylbutanoic acid: P =. 01, AUROC = 0.79-0.80). In addition, bacteria identified from BAL cultures that are known to metabolize tryptophan (E. coli, Klebsiella oxytoca, and Haemophilus influenzae) were grouped and found to produce higher concentrations of indole compared to breath samples with culture-negative (P =. 034) and other pathogen-positive (P =. 049) samples. Conclusions: This study demonstrates the capability of using mVOCs to detect the presence of specific pathogen groups with potential to support clinical diagnosis. Although not all mVOCs were found in patient samples within this small pilot study, further targeted and qualitative investigation is warranted using multicenter clinical studies.
AB - Background: Early and accurate recognition of respiratory pathogens is crucial to prevent increased risk of mortality in critically ill patients. Microbial-derived volatile organic compounds (mVOCs) in exhaled breath could be used as noninvasive biomarkers of infection to support clinical diagnosis. Methods: In this study, we investigated the diagnostic potential of in vitro-confirmed mVOCs in the exhaled breath of patients under mechanical ventilation from the BreathDx study. Samples were analyzed by thermal desorption-gas chromatography-mass spectrometry. Results: Pathogens from bronchoalveolar lavage (BAL) cultures were identified in 45 of 89 patients and Staphylococcus aureus was the most commonly identified pathogen (n = 15). Of 19 mVOCs detected in the in vitro culture headspace of 4 common respiratory pathogens (S. aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli), 14 were found in exhaled breath samples. Higher concentrations of 2 mVOCs were found in the exhaled breath of patients infected with S. aureus compared to those without (3-methylbutanal: P <. 01, area under the receiver operating characteristic curve [AUROC] = 0.81-0.87; and 3-methylbutanoic acid: P =. 01, AUROC = 0.79-0.80). In addition, bacteria identified from BAL cultures that are known to metabolize tryptophan (E. coli, Klebsiella oxytoca, and Haemophilus influenzae) were grouped and found to produce higher concentrations of indole compared to breath samples with culture-negative (P =. 034) and other pathogen-positive (P =. 049) samples. Conclusions: This study demonstrates the capability of using mVOCs to detect the presence of specific pathogen groups with potential to support clinical diagnosis. Although not all mVOCs were found in patient samples within this small pilot study, further targeted and qualitative investigation is warranted using multicenter clinical studies.
KW - exhaled volatile organic compounds
KW - gas chromatography-mass spectrometry
KW - hospital-acquired infection
UR - http://www.scopus.com/inward/record.url?scp=85157986950&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/cid/ciac859
DO - https://doi.org/10.1093/cid/ciac859
M3 - Article
C2 - 36310531
SN - 1058-4838
VL - 76
SP - 1059
EP - 1066
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 6
ER -