460368b56a837ed4c2fa1862afbe3c28 antibiotics-14-00594.pdf 433be11ade191a5435ea63b0b373d83fbb36fa0e antibiotics-14-00594.pdf 3ba3e18cffd4946f5effecdf9d6a0110fe4626079b40a62f04946a06c7b50516 antibiotics-14-00594.pdf Title: Does Empirical Antibiotic Use Improve Outcomes in Ventilated Patients with Pandemic Viral Infection? A Multicentre Retrospective Study Subject: Background: During the influenza A(H1N1) and COVID-19 pandemics, empirical antibiotic treatment (EAT) was widely administered to critically ill patients despite low rates of confirmed bacterial co-infection (COI). The clinical benefit of this practice remains uncertain and may contradict antimicrobial stewardship principles. Objective: To evaluate whether EAT at ICU admission reduces ventilator-associated pneumonia (VAP) incidence or ICU mortality in critically ill patients with pandemic viral pneumonia, stratified by presence of COI. Methods: This retrospective analysis combined two national multicentre ICU registries in Spain, including 4197 adult patients requiring invasive mechanical ventilation for influenza A(H1N1) or COVID-19 between 2009 and 2021. Primary outcomes were ICU mortality and VAP incidence. Analyses were stratified by microbiologically confirmed bacterial COI. Propensity score matching, Cox regression, General Linear (GLM), and random forest models were applied. Results: Among patients without COI (n = 3543), EAT was not associated with lower ICU mortality (OR = 1.02, 95%CI 0.81–1.28, p = 0.87) or VAP (OR = 1.02, 95%CI 0.79–1.39, p = 0.89). In patients with confirmed COI (n = 654), appropriate EAT was associated with reduced VAP (17.4% vs. 36.3%, p < 0.001) and ICU mortality (38.4% vs. 49.6%, OR = 1.89, 95%CI 1.13–3.14, p = 0.03) compared to inappropriate EAT. Conclusions: EAT was not associated with a lower incidence of VAP or higher survival rates and could be harmful if administered incorrectly. These findings support a more targeted approach to antibiotic use, guided by microbiology, biomarkers and stewardship principles. Keywords: empirical antibiotic treatment; pandemic viral pneumonia; ventilator-associated pneumonia; ICU mortality; antimicrobial stewardship Author: Elisabeth Papiol, Julen Berrueta, Juan Carlos Ruíz-Rodríguez, Ricard Ferrer, Sara Manrique, Laura Claverias, Alejandro García-Martínez, Pau Orts, Emili Díaz, Rafael Zaragoza, Marco Marotta, María Bodí, Sandra Trefler, Josep Gómez, Ignacio Martín-Loeches and Alejandro Rodríguez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Mon Jun 9 10:09:13 2025 CEST ModDate: Mon Jun 9 10:13:49 2025 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 20 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4072605 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OXTKEE+VnURWPalladioL Type 1 Custom yes yes yes 10 0 BHLWBX+URWPalladioL-Roma Type 1 Custom yes yes yes 16 0 UBYCTM+URWPalladioL-Bold Type 1 Custom yes yes yes 22 0 IMYHEW+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 TBOZEP+URWPalladioL-BoldItal Type 1 Custom yes yes yes 59 0 DVCMRV+CMSY10 Type 1 Builtin yes yes yes 64 0 IOOBKF+PalatinoLinotype TrueType WinAnsi yes yes no 81 0 IOOBKF+PalatinoLinotype TrueType WinAnsi yes yes no 126 0 IOOBKH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 129 0 IOOBKF+PalatinoLinotype TrueType WinAnsi yes yes no 136 0 IOOBKH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 139 0 IOOBKF+PalatinoLinotype TrueType WinAnsi yes yes no 151 0 IOOBKH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 154 0 IOOBKF+PalatinoLinotype TrueType WinAnsi yes yes no 164 0 IOOBKH+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 167 0 IOOBKF+PalatinoLinotype TrueType WinAnsi yes yes no 178 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-07-11 02:43:58 CEST RepresentationInformation: antibiotics-14-00594.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-07-10 18:14:32 CEST Size: 4072605 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 398 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Design Destination: subsection.2.1 Item: Title: Setting Destination: subsection.2.2 Item: Title: Participants Destination: subsection.2.3 Item: Title: Variables Destination: subsection.2.4 Item: Title: Data Sources and Measurement Destination: subsection.2.5 Item: Title: Bias Destination: subsection.2.6 Item: Title: Analysis Plan and Statistical Analysis (Figure 1) Destination: subsection.2.7 Item: Title: Results Destination: section.3 Children: Item: Title: Whole Population Destination: subsection.3.1 Item: Title: Patients with Bacterial Coinfection (COI) Destination: subsection.3.2 Item: Title: Patients Without Bacterial Coinfection (No-COI) Destination: subsection.3.3 Item: Title: Linear Models in Matched Cohort of Patients Without Coinfection Destination: subsection.3.4 Children: Item: Title: Risk Factors Associated with the Development of Ventilator-Associated Pneumonia (VAP) Destination: subsubsection.3.4.1 Item: Title: Risk Factors Associated with All-Cause ICU Mortality Destination: subsubsection.3.4.2 Item: Title: Non-Linear Analysis Random Forest Model (RF) Destination: subsection.3.5 Children: Item: Title: Factors Associated with VAP According to Non-Linear Model Destination: subsubsection.3.5.1 Item: Title: Factors Associated with All-Cause ICU Mortality According to No-Linear Model Destination: subsubsection.3.5.2 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Does Empirical Antibiotic Use Improve Outcomes in Ventilated Patients with Pandemic Viral Infection? A Multicentre Retrospective Study Author: Elisabeth Papiol, Julen Berrueta, Juan Carlos Ruíz-Rodríguez, Ricard Ferrer, Sara Manrique, Laura Claverias, Alejandro García-Martínez, Pau Orts, Emili Díaz, Rafael Zaragoza, Marco Marotta, María Bodí, Sandra Trefler, Josep Gómez, Ignacio Martín-Loeches and Alejandro Rodríguez Subject: Background: During the influenza A(H1N1) and COVID-19 pandemics, empirical antibiotic treatment (EAT) was widely administered to critically ill patients despite low rates of confirmed bacterial co-infection (COI). The clinical benefit of this practice remains uncertain and may contradict antimicrobial stewardship principles. Objective: To evaluate whether EAT at ICU admission reduces ventilator-associated pneumonia (VAP) incidence or ICU mortality in critically ill patients with pandemic viral pneumonia, stratified by presence of COI. Methods: This retrospective analysis combined two national multicentre ICU registries in Spain, including 4197 adult patients requiring invasive mechanical ventilation for influenza A(H1N1) or COVID-19 between 2009 and 2021. Primary outcomes were ICU mortality and VAP incidence. Analyses were stratified by microbiologically confirmed bacterial COI. Propensity score matching, Cox regression, General Linear (GLM), and random forest models were applied. Results: Among patients without COI (n = 3543), EAT was not associated with lower ICU mortality (OR = 1.02, 95%CI 0.81 1.28, p = 0.87) or VAP (OR = 1.02, 95%CI 0.79 1.39, p = 0.89). In patients with confirmed COI (n = 654), appropriate EAT was associated with reduced VAP (17.4% vs. 36.3%, p < 0.001) and ICU mortality (38.4% vs. 49.6%, OR = 1.89, 95%CI 1.13 3.14, p = 0.03) compared to inappropriate EAT. Conclusions: EAT was not associated with a lower incidence of VAP or higher survival rates and could be harmful if administered incorrectly. These findings support a more targeted approach to antibiotic use, guided by microbiology, biomarkers and stewardship principles. Keywords: empirical antibiotic treatment; pandemic viral pneumonia; ventilator-associated pneumonia; ICU mortality; antimicrobial stewardship Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Mon Jun 09 10:09:13 CEST 2025 ModDate: Mon Jun 09 10:13:49 CEST 2025 ID: 0x99c590d87d1b8d7d8aaf59209492b241, 0x99c590d87d1b8d7d8aaf59209492b241 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: BHLWBX+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 250 FontDescriptor: FontName: BHLWBX+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: DVCMRV+CMSY10 FontSubset: true FirstChar: 2 LastChar: 2 FontDescriptor: FontName: DVCMRV+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true ToUnicode: true Font: BaseFont: UBYCTM+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 243 FontDescriptor: FontName: UBYCTM+URWPalladioL-Bold Flags: Symbolic 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