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In critically ill patients, anti-anaerobic antibiotics increase risk of adverse clinical outcomes

BACKGROUND: Critically ill patients routinely receive antibiotics with activity against anaerobic gut bacteria. However, in other disease states and animal models, gut anaerobes are protective against pneumonia, organ failure and mortality. We therefore designed a translational series of analyses an...

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Autores principales: Chanderraj, Rishi, Baker, Jennifer M., Kay, Stephen G., Brown, Christopher A., Hinkle, Kevin J., Fergle, Daniel J., McDonald, Roderick A., Falkowski, Nicole R., Metcalf, Joseph D., Kaye, Keith S., Woods, Robert J., Prescott, Hallie C., Sjoding, Michael W., Dickson, Robert P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: European Respiratory Society 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909213/
https://www.ncbi.nlm.nih.gov/pubmed/36229047
http://dx.doi.org/10.1183/13993003.00910-2022
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author Chanderraj, Rishi
Baker, Jennifer M.
Kay, Stephen G.
Brown, Christopher A.
Hinkle, Kevin J.
Fergle, Daniel J.
McDonald, Roderick A.
Falkowski, Nicole R.
Metcalf, Joseph D.
Kaye, Keith S.
Woods, Robert J.
Prescott, Hallie C.
Sjoding, Michael W.
Dickson, Robert P.
author_facet Chanderraj, Rishi
Baker, Jennifer M.
Kay, Stephen G.
Brown, Christopher A.
Hinkle, Kevin J.
Fergle, Daniel J.
McDonald, Roderick A.
Falkowski, Nicole R.
Metcalf, Joseph D.
Kaye, Keith S.
Woods, Robert J.
Prescott, Hallie C.
Sjoding, Michael W.
Dickson, Robert P.
author_sort Chanderraj, Rishi
collection PubMed
description BACKGROUND: Critically ill patients routinely receive antibiotics with activity against anaerobic gut bacteria. However, in other disease states and animal models, gut anaerobes are protective against pneumonia, organ failure and mortality. We therefore designed a translational series of analyses and experiments to determine the effects of anti-anaerobic antibiotics on the risk of adverse clinical outcomes among critically ill patients. METHODS: We conducted a retrospective single-centre cohort study of 3032 critically ill patients, comparing patients who did and did not receive early anti-anaerobic antibiotics. We compared intensive care unit outcomes (ventilator-associated pneumonia (VAP)-free survival, infection-free survival and overall survival) in all patients and changes in gut microbiota in a subcohort of 116 patients. In murine models, we studied the effects of anaerobe depletion in infectious (Klebsiella pneumoniae and Staphylococcus aureus pneumonia) and noninfectious (hyperoxia) injury models. RESULTS: Early administration of anti-anaerobic antibiotics was associated with decreased VAP-free survival (hazard ratio (HR) 1.24, 95% CI 1.06–1.45), infection-free survival (HR 1.22, 95% CI 1.09–1.38) and overall survival (HR 1.14, 95% CI 1.02–1.28). Patients who received anti-anaerobic antibiotics had decreased initial gut bacterial density (p=0.00038), increased microbiome expansion during hospitalisation (p=0.011) and domination by Enterobacteriaceae spp. (p=0.045). Enterobacteriaceae were also enriched among respiratory pathogens in anti-anaerobic-treated patients (p<2.2×10(−16)). In murine models, treatment with anti-anaerobic antibiotics increased susceptibility to Enterobacteriaceae pneumonia (p<0.05) and increased the lethality of hyperoxia (p=0.0002). CONCLUSIONS: In critically ill patients, early treatment with anti-anaerobic antibiotics is associated with increased mortality. Mechanisms may include enrichment of the gut with respiratory pathogens, but increased mortality is incompletely explained by infections alone. Given consistent clinical and experimental evidence of harm, the widespread use of anti-anaerobic antibiotics should be reconsidered.
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spelling pubmed-99092132023-02-09 In critically ill patients, anti-anaerobic antibiotics increase risk of adverse clinical outcomes Chanderraj, Rishi Baker, Jennifer M. Kay, Stephen G. Brown, Christopher A. Hinkle, Kevin J. Fergle, Daniel J. McDonald, Roderick A. Falkowski, Nicole R. Metcalf, Joseph D. Kaye, Keith S. Woods, Robert J. Prescott, Hallie C. Sjoding, Michael W. Dickson, Robert P. Eur Respir J Original Research Articles BACKGROUND: Critically ill patients routinely receive antibiotics with activity against anaerobic gut bacteria. However, in other disease states and animal models, gut anaerobes are protective against pneumonia, organ failure and mortality. We therefore designed a translational series of analyses and experiments to determine the effects of anti-anaerobic antibiotics on the risk of adverse clinical outcomes among critically ill patients. METHODS: We conducted a retrospective single-centre cohort study of 3032 critically ill patients, comparing patients who did and did not receive early anti-anaerobic antibiotics. We compared intensive care unit outcomes (ventilator-associated pneumonia (VAP)-free survival, infection-free survival and overall survival) in all patients and changes in gut microbiota in a subcohort of 116 patients. In murine models, we studied the effects of anaerobe depletion in infectious (Klebsiella pneumoniae and Staphylococcus aureus pneumonia) and noninfectious (hyperoxia) injury models. RESULTS: Early administration of anti-anaerobic antibiotics was associated with decreased VAP-free survival (hazard ratio (HR) 1.24, 95% CI 1.06–1.45), infection-free survival (HR 1.22, 95% CI 1.09–1.38) and overall survival (HR 1.14, 95% CI 1.02–1.28). Patients who received anti-anaerobic antibiotics had decreased initial gut bacterial density (p=0.00038), increased microbiome expansion during hospitalisation (p=0.011) and domination by Enterobacteriaceae spp. (p=0.045). Enterobacteriaceae were also enriched among respiratory pathogens in anti-anaerobic-treated patients (p<2.2×10(−16)). In murine models, treatment with anti-anaerobic antibiotics increased susceptibility to Enterobacteriaceae pneumonia (p<0.05) and increased the lethality of hyperoxia (p=0.0002). CONCLUSIONS: In critically ill patients, early treatment with anti-anaerobic antibiotics is associated with increased mortality. Mechanisms may include enrichment of the gut with respiratory pathogens, but increased mortality is incompletely explained by infections alone. Given consistent clinical and experimental evidence of harm, the widespread use of anti-anaerobic antibiotics should be reconsidered. European Respiratory Society 2023-02-09 /pmc/articles/PMC9909213/ /pubmed/36229047 http://dx.doi.org/10.1183/13993003.00910-2022 Text en The content of this work is not subject to copyright. Design and branding are copyright ©ERS 2023. https://creativecommons.org/licenses/by-nc/4.0/This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org (mailto:permissions@ersnet.org)
spellingShingle Original Research Articles
Chanderraj, Rishi
Baker, Jennifer M.
Kay, Stephen G.
Brown, Christopher A.
Hinkle, Kevin J.
Fergle, Daniel J.
McDonald, Roderick A.
Falkowski, Nicole R.
Metcalf, Joseph D.
Kaye, Keith S.
Woods, Robert J.
Prescott, Hallie C.
Sjoding, Michael W.
Dickson, Robert P.
In critically ill patients, anti-anaerobic antibiotics increase risk of adverse clinical outcomes
title In critically ill patients, anti-anaerobic antibiotics increase risk of adverse clinical outcomes
title_full In critically ill patients, anti-anaerobic antibiotics increase risk of adverse clinical outcomes
title_fullStr In critically ill patients, anti-anaerobic antibiotics increase risk of adverse clinical outcomes
title_full_unstemmed In critically ill patients, anti-anaerobic antibiotics increase risk of adverse clinical outcomes
title_short In critically ill patients, anti-anaerobic antibiotics increase risk of adverse clinical outcomes
title_sort in critically ill patients, anti-anaerobic antibiotics increase risk of adverse clinical outcomes
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909213/
https://www.ncbi.nlm.nih.gov/pubmed/36229047
http://dx.doi.org/10.1183/13993003.00910-2022
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