Prophetic EU: Prospective Identification of Pneumonia in Hospitalized Patients in the Intensive Care Unit–A Comparison of European and United States Cohorts

Background: Prospective identification of patients at high risk of nosocomial pneumonia may improve clinical trial feasibility and foster antibacterial development. Clinical criteria prospectively identified patients at highest risk of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in the United States (US). Whether these findings are applicable in a European population is unknown. Methods: Adults considered high risk for pneumonia (treatment with ventilation or high levels of supplemental oxygen) in the intensive care units of seven European hospitals were prospectively enrolled. We estimated the proportion of high-risk patients developing HABP/VABP, defined according to US Food and Drug Administration (FDA) guidance, and the subset potentially eligible for antibacterial trial enrollment. We compared patient characteristics, exposures, and HABP/VABP incidence in European and US cohorts. Findings: Of 888 high-risk patients enrolled between June 12 and December 27, 2017, 211/888 (24%) were treated for possible pneumonia and 150/888 (17%) met the FDA definition for HABP/VABP. A higher proportion of European high-risk patients treated for possible pneumonia met the HABP/VABP definition (150/211 [71%] versus 537/1464 [37%] in US, p<0·001). Among patients developing HABP/VABP, a higher proportion in the European cohort met antibacterial trial eligibility criteria (124/150 [83%] versus 371/537 [69%], p<0·001). Interpretation: Readily available clinical criteria prospectively identified patients with high rates of HABP/VABP in this European cohort of high-risk patients. Despite higher rates of established risk factors and incident HABP/VABP, European high-risk patients were significantly less likely to receive antibiotics for possible pneumonia than US patients. Different treatment practices may contribute to lower rates of antibacterial trial enrollment observed in the US. Funding: U.S. Food and Drug Administration Declaration of Interest: SP Bergin: Dr. Bergin reports consulting for Aridis Pharmaceuticals and C3J Therapeutics. SB Calvert: Dr. Calvert reports salary support from the U.S. FDA grant R18FD005292 and CTTI membership fees. J Farley: Dr. Farley reports no conflicts related to this work. J-L Sun: Ms. Sun reports no conflicts related to this work. K Chiswell: Dr. Chiswell reports no conflicts related to this work. W Dieperink: Dr. Dieperink reports no conflicts related to this work. J Kluytmans: Dr. Kluytmans reports no conflicts related to this work. JC Lopez-Delgado: Dr. Lopez-Delgado reports no conflicts related to this work. R Leon-Lopez: Dr. Leon-Lopez reports no conflicts related to this work. MJ Zervos: Dr. Zervos reports serving as a consultant for ContraFect and receiving research grants from Merck, Moderna, Janssen, Pfizer, and Serono. MH Kollef: Dr. Kollef reports support by the Barnes-Jewish Hospital Foundation. M Sims: Dr. Sims reports grants from Aridis Pharmaceuticals Inc, Cidara Therapeutics, ContraFect, Cubist Pharmaceuticals Inc (now Merck), Curetis Ag, Curetis GmBM, CutisPharma, DiaSorin Molecular LLC, Epigenomics Inc, EUROIMMUN US, Finch Therapeutics, Genentech USA Inc, Gilead Sciences, IBIS Biosystems, Iterum Therapeutics, Janssen Research and Development, LLC, Kinevant Sciences GmBH, Leonard-Meron Biosciences, Merck, Nabriva Therapeutics, NeuMoDx Molecular, Paratek Pharmaceuticals, Pfizer, Prenosis, Regeneron Pharmaceuticals, Sanofi Pasteur Inc, Seres Therapeutics Inc, Shire, Summit Therapeutics BA Kabchi: Dr. Kabchi reports no conflicts related to this work. D Rubin: Dr. Rubin reports no conflicts related to this work. J Santiago: Dr. Santiago reports no conflicts related to this work. M Natarajan: Dr. Natarajan reports no conflicts related to this work. P Tenaerts: Dr. Tenaerts reports salary support from the U.S. FDA grant R18FD005292 and CTTI membership fees. VG Fowler Jr.: Dr. Fowler 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. TL Holland: Dr. Holland reports consulting for Basilea Pharmaceutica (ceftobiprole), Genentech (immunotherapeutic), Motif Bio (iclaprim), Aridis (monoclonal antibody) and Lysovant (lysin). MJ Bonten: Mr. Bonten reports no conflicts related to this work. SJ Hullegie: Mr. Hullegie reports grants from ZonMW, outside the submitted work. Ethical Approval: The study protocol was approved, and a waiver of informed consent was granted by an independent review board (Copernicus Group, CTTI_001, DCR2-15-710), or when required, the institutional review board of participating US institutions, and by ethics committees of each country in Europe.