TY - JOUR
T1 - PROPHETIC
T2 - Prospective Identification of Pneumonia in Hospitalized Patients in the ICU
AU - Bergin, Stephen P.
AU - Coles, Adrian
AU - Calvert, Sara B.
AU - Farley, John
AU - Powers, John H.
AU - Zervos, Marcus J.
AU - Sims, Matthew
AU - Kollef, Marin H.
AU - Durkin, Michael J.
AU - Kabchi, Badih A.
AU - Donnelly, Helen K.
AU - Bardossy, Ana Cecilia
AU - Greenshields, Claire
AU - Rubin, Daniel
AU - Sun, Jie Lena
AU - Chiswell, Karen
AU - Santiago, Jonas
AU - Gu, Peidi
AU - Tenaerts, Pamela
AU - Fowler, Vance G.
AU - Holland, Thomas L.
N1 - Funding Information:
FUNDING/SUPPORT: This study was funded by the Food and Drug Administration through grant R18FD005292 and partially funded by pooled membership fees from CTTI’s member organizations ( https://www.ctti-clinicaltrials.org/membership ); V. G. F. was supported by mid-career mentoring award K24-AI093969 from the National Institutes of Health .
Funding Information:
FUNDING/SUPPORT: This study was funded by the Food and Drug Administration through grant R18FD005292 and partially funded by pooled membership fees from CTTI's member organizations (https://www.ctti-clinicaltrials.org/membership); V. G. F. was supported by mid-career mentoring award K24-AI093969 from the National Institutes of Health.Author contributions: S. P. B. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. S. P. B and A. C. contributed to the conception and design of the study, the data analysis, the data interpretation, the manuscript drafting, and the critical revision of the manuscript. S. B. C. J. F. J. H. P. H. K. D. D. R. and P. T. contributed to the conception and design of the study, data interpretation, the manuscript drafting, and the critical revision of the manuscript. M. J. Z. M. S. M. H. K. M. J. D. B. A. K. A. C. B. C. G. J. S. and P. G. contributed to the data interpretation, the manuscript drafting, and the critical revision of the manuscript. J.-L. S. and K. C. contributed to data analysis, the data interpretation, the manuscript drafting, and the critical revision of the manuscript. V. G. F. contributed to the conception and design of the study, the supervision, data interpretation, the manuscript drafting, and the critical revision of the manuscript. T. L. H. contributed to the conception and design of the study, the supervision, data acquisition, analysis and interpretation, the manuscript drafting, and the critical revision of the manuscript. Financial/nonfinancial disclosures: The authors have reported to CHEST the following: S. B. C. reports salary support from the US FDA grant R18FD005292 and CTTI membership fees. M. J. Z. reports serving on an adjudication committee for ContraFect and receiving research grants from Genentech, Medimune, and Merck. M. S. reports consulting for Curetis GmBH, Paratek Pharmaceuticals, and Cutis Pharma, receiving a grant from Cubist Pharmaceuticals Inc (Now Merck and Co), receiving research support from Astra Zeneca Pharmaceuticals LP, Cempra Inc, Aradigm Corp, Cubist Pharmaceuticals Inc (Now Merck and Co), Synthetic Biologics Inc, Deibopharm International SA, Bayer HealthCare AG, Theravance Inc, Seres Therapeutics Inc, Rempex, Vela Diagnostics, AM-Pharma, Abbott Molecular Inc, Gilead Sciences Inc, Merck and Co, NeuMoDx Molecular, Nabriva Therapeutics AG, Sanofi Pasteur Inc, Diasorin Molecular, Curetis GmbH, Pfizer Inc, Cidara Therapeutics Inc, Shire, ContraFect, Aridis Pharmaceuticals Inc, Epigenomics Inc, Genentech Inc, Finch Therapeutics, MedImmune, Janssen Research and Development LLC, The Medicines Company, Summit Therapeutics, Iterum Therapeutics International, outside the submitted work; in addition, he has a patent Methods of diagnosing increased risk of developing MRSA or CA-MRSA issued, and a patent DETECTING AND TREATING MRSA and SSI pending. M. H. K. reports support from the Barnes-Jewish Hospital Foundation. M. J. D. reports funding from the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number KL2TR002346. P. T. reports salary support from the US FDA grant R18FD005292 and CTTI membership fees. V. G. F. reports serving as chair of the V710 Scientific Advisory Committee (Merck); has received grant support from Cerexa/Actavis/Allergan, Pfizer, Advanced Liquid Logics, NIH, MedImmune, Basilea Pharmaceutica, Karius, ContraFect, Regeneron Pharmaceuticals, and Genentech; has NIH Small Business Technology Transfer/Small Business Innovation Research grants pending with Affinergy, Locus, and Medical Surface; has been a consultant for Achaogen, Astellas Pharma, Arsanis, Affinergy, Basilea Pharmaceutica, Bayer, Cerexa Inc, ContraFect, Cubist, Debiopharm, Durata Therapeutics, Grifols, Genentech, MedImmune, Merck, the Medicines Company, Pfizer, Novartis, NovaDigm Therapeutics Inc, Theravance Biopharma, and XBiotech; has received honoraria from Theravance Biopharma and Green Cross; and has a patent pending in sepsis diagnostics. T. L. H. reports consulting for Basilea Pharmaceutica (ceftobiprole), Genentech (immunotherapeutic), Motif Bio (iclaprim), and Theravance (telavancin). None declared (S. P. B. A. C. J. F. J. H. P. B. A. K. H. K. D. A. C. B. C. G. D. R. J.-L. S. K. C. J. S. and P. G.). Role of sponsors: The FDA and CTTI membership fees funded the study; members of the both the FDA and CTTI were part of the study team. FDA and CTTI authors contributed to the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Other contributions: The authors would like to thank the PROPHETIC study investigators and coordinators for conducting the study, the CTTI HABP/VABP studies project team (https://www.ctti-clinicaltrials.org/projects/habpvabp-studies) for contributions to the concept and design of the study, and Erin Campbell for editorial support. Views expressed in this manuscript do not necessarily reflect the official policies of the Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organization imply endorsement by the United States Government. Additional information: The e-Appendix, e-Figures, and e-Tables can be found in the Supplemental Materials section of the online article.
Publisher Copyright:
© 2020 American College of Chest Physicians
PY - 2020/12
Y1 - 2020/12
N2 - Background: Pneumonia is the leading infection-related cause of death. The use of simple clinical criteria and contemporary epidemiology to identify patients at high risk of nosocomial pneumonia should enhance prevention efforts and facilitate development of new treatments in clinical trials. Research Question: What are the clinical criteria and contemporary epidemiology trends that are helpful in the identification of patients at high risk of nosocomial pneumonia? Study Design and Methods: Within the ICUs of 28 US hospitals, we conducted a prospective cohort study among adults who had been hospitalized >48 hours and were considered high risk for pneumonia (defined as treatment with invasive or noninvasive ventilatory support or high levels of supplemental oxygen). We estimated the proportion of high-risk patients who experienced the development of nosocomial pneumonia. Using multivariable logistic regression, we identified patient characteristics and treatment exposures that are associated with increased risk of pneumonia development during the ICU admission. Results: Between February 6, 2016, and October 7, 2016, 4,613 high-risk patients were enrolled. Among 1,464 high-risk patients (32%) who were treated for possible nosocomial pneumonia, 537 (37%) met the study pneumonia definition. Among high-risk patients, a multivariable logistic model was developed to identify key patient characteristics and treatment exposures that are associated with increased risk of nosocomial pneumonia development (c-statistic, 0.709; 95% CI, 0.686-0.731). Key factors associated with increased odds of nosocomial pneumonia included an admission diagnosis of trauma or cerebrovascular accident, receipt of enteral nutrition, documented aspiration risk, and receipt of systemic antibacterials within the preceding 90 days. Interpretation: Treatment for nosocomial pneumonia is common among patients in the ICU who are receiving high levels of respiratory support, yet more than one-half of patients who are treated do not fulfill standard diagnostic criteria for pneumonia. Application of simple clinical criteria may improve the feasibility of clinical trials of pneumonia prevention and treatment by facilitating prospective identification of patients at highest risk.
AB - Background: Pneumonia is the leading infection-related cause of death. The use of simple clinical criteria and contemporary epidemiology to identify patients at high risk of nosocomial pneumonia should enhance prevention efforts and facilitate development of new treatments in clinical trials. Research Question: What are the clinical criteria and contemporary epidemiology trends that are helpful in the identification of patients at high risk of nosocomial pneumonia? Study Design and Methods: Within the ICUs of 28 US hospitals, we conducted a prospective cohort study among adults who had been hospitalized >48 hours and were considered high risk for pneumonia (defined as treatment with invasive or noninvasive ventilatory support or high levels of supplemental oxygen). We estimated the proportion of high-risk patients who experienced the development of nosocomial pneumonia. Using multivariable logistic regression, we identified patient characteristics and treatment exposures that are associated with increased risk of pneumonia development during the ICU admission. Results: Between February 6, 2016, and October 7, 2016, 4,613 high-risk patients were enrolled. Among 1,464 high-risk patients (32%) who were treated for possible nosocomial pneumonia, 537 (37%) met the study pneumonia definition. Among high-risk patients, a multivariable logistic model was developed to identify key patient characteristics and treatment exposures that are associated with increased risk of nosocomial pneumonia development (c-statistic, 0.709; 95% CI, 0.686-0.731). Key factors associated with increased odds of nosocomial pneumonia included an admission diagnosis of trauma or cerebrovascular accident, receipt of enteral nutrition, documented aspiration risk, and receipt of systemic antibacterials within the preceding 90 days. Interpretation: Treatment for nosocomial pneumonia is common among patients in the ICU who are receiving high levels of respiratory support, yet more than one-half of patients who are treated do not fulfill standard diagnostic criteria for pneumonia. Application of simple clinical criteria may improve the feasibility of clinical trials of pneumonia prevention and treatment by facilitating prospective identification of patients at highest risk.
KW - ICU
KW - nosocomial
KW - pneumonia
UR - http://www.scopus.com/inward/record.url?scp=85096689724&partnerID=8YFLogxK
U2 - 10.1016/j.chest.2020.06.034
DO - 10.1016/j.chest.2020.06.034
M3 - Article
C2 - 32615191
AN - SCOPUS:85096689724
SN - 0012-3692
VL - 158
SP - 2370
EP - 2380
JO - Chest
JF - Chest
IS - 6
ER -