Empirical antibiotic therapy improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study

Bacterial pulmonary superinfections develop in a substantial proportion of mechanically ventilated COVID-19 patients and are associated with prolonged mechanical ventilation requirements and increased mortality. Albeit recommended, evidence supporting the use of empirical antibiotics at intubation i...

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Published in:The Journal of infection 2025-02, Vol.90 (2), p.106411, Article 106411
Main Authors: Wendel-Garcia, Pedro D., Ceccato, Adrian, Motos, Ana, Franch-Llasat, Diego, Pérez-Moreno, Mar O., Domenech-Spanedda, Marie F., Chamarro-Martí, Elena, Ferrer, Ricard, Fernández-Barat, Laia, Riera, Jordi, Álvarez-Napagao, Sergio, Peñuelas, Oscar, Lorente, Jose A., Almansa, Raquel, Gabarrús, Albert, de Gonzalo-Calvo, David, González, Jessica, Añon, Jose M., Barberà, Carme, Barberán, José, Blandino-Ortiz, Aaron, Bustamante-Munguira, Elena, Caballero, Jesús, Carbajales-Pérez, Cristina, Carbonell, Nieves, Catalán-González, Mercedes, Barral-Segade, Patricia, Mañez, Rafael, de la Torre, Mari C., Díaz, Emili, Estella, Ángel, Gallego, Elena, García-Garmendia, José L., Garnacho-Montero, José, Amaya-Villar, Rosario, Gómez, José M., Huerta, Arturo, Jorge-García, Ruth N., Loza-Vázquez, Ana, Marin-Corral, Judith, Martin-Delgado, María Cruz, de la Gándara, Amalia Martínez, Martínez-Varela, Ignacio Y., López-Messa, Juan, Muñiz-Albaiceta, Guillermo, Novo, Mariana A., Peñasco, Yhivian, Pozo-Laderas, Juan C., Ricart, Pilar, Sánchez-Miralles, Ángel, Sancho, Susana, Socias, Lorenzo, Solé-Violan, Jordi, Suárez-Sipmann, Fernando, Tamayo, Luis, Trenado, José, Barbé, Ferran, Torres, Antoni, Roche-Campo, Ferran
Format: Article
Language:English
Subjects:
Bacterial coinfections
Bacterial superinfections
Critically ill
Prophylactic antibiotics
Ventilator-associated pneumonia
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container_start_page 106411
container_title The Journal of infection
container_volume 90
creator Wendel-Garcia, Pedro D.
Ceccato, Adrian
Motos, Ana
Franch-Llasat, Diego
Pérez-Moreno, Mar O.
Domenech-Spanedda, Marie F.
Chamarro-Martí, Elena
Ferrer, Ricard
Fernández-Barat, Laia
Riera, Jordi
Álvarez-Napagao, Sergio
Peñuelas, Oscar
Lorente, Jose A.
Almansa, Raquel
Gabarrús, Albert
de Gonzalo-Calvo, David
González, Jessica
Añon, Jose M.
Barberà, Carme
Barberán, José
Blandino-Ortiz, Aaron
Bustamante-Munguira, Elena
Caballero, Jesús
Carbajales-Pérez, Cristina
Carbonell, Nieves
Catalán-González, Mercedes
Barral-Segade, Patricia
Mañez, Rafael
de la Torre, Mari C.
Díaz, Emili
Estella, Ángel
Gallego, Elena
García-Garmendia, José L.
Garnacho-Montero, José
Amaya-Villar, Rosario
Gómez, José M.
Huerta, Arturo
Jorge-García, Ruth N.
Loza-Vázquez, Ana
Marin-Corral, Judith
Martin-Delgado, María Cruz
de la Gándara, Amalia Martínez
Martínez-Varela, Ignacio Y.
López-Messa, Juan
Muñiz-Albaiceta, Guillermo
Novo, Mariana A.
Peñasco, Yhivian
Pozo-Laderas, Juan C.
Ricart, Pilar
Sánchez-Miralles, Ángel
Sancho, Susana
Socias, Lorenzo
Solé-Violan, Jordi
Suárez-Sipmann, Fernando
Tamayo, Luis
Trenado, José
Barbé, Ferran
Torres, Antoni
Roche-Campo, Ferran
description Bacterial pulmonary superinfections develop in a substantial proportion of mechanically ventilated COVID-19 patients and are associated with prolonged mechanical ventilation requirements and increased mortality. Albeit recommended, evidence supporting the use of empirical antibiotics at intubation is weak and of low quality. The aim of this study was to elucidate the effect of empirical antibiotics, administered within 24 h of endotracheal intubation, on superinfections, duration of mechanical ventilation, and mortality in mechanically ventilated patients with COVID-19. Emulated targeted trial by means of a propensity score-matched analysis of a prospective multicentre cohort study of consecutive mechanically ventilated patients admitted to 62 Spanish intensive care units suffering from COVID-19 between March 2020 and February 2021. Overall, 8532 critically ill COVID-19 patients were included, of which 2580 mechanically ventilated patients remained after matching. Empirical antibiotics were prescribed to 1665 (64%) at intubation. Pulmonary superinfections developed in 39% and 47% of patients treated with and without empirical antibiotics, respectively (p
doi_str_mv 10.1016/j.jinf.2025.106411
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Albeit recommended, evidence supporting the use of empirical antibiotics at intubation is weak and of low quality. The aim of this study was to elucidate the effect of empirical antibiotics, administered within 24 h of endotracheal intubation, on superinfections, duration of mechanical ventilation, and mortality in mechanically ventilated patients with COVID-19. Emulated targeted trial by means of a propensity score-matched analysis of a prospective multicentre cohort study of consecutive mechanically ventilated patients admitted to 62 Spanish intensive care units suffering from COVID-19 between March 2020 and February 2021. Overall, 8532 critically ill COVID-19 patients were included, of which 2580 mechanically ventilated patients remained after matching. Empirical antibiotics were prescribed to 1665 (64%) at intubation. Pulmonary superinfections developed in 39% and 47% of patients treated with and without empirical antibiotics, respectively (p&lt;0.01). Patients treated with empirical antibiotics had a shorter duration of mechanical ventilation (incidence risk ratio: 0.85 [95% confidence interval (CI), 0.78 – 0.94], p&lt;0.01) and a reduced stay in the intensive care unit (incidence risk ratio: 0.89 [95% CI, 0.82 – 0.97] days, p&lt;0.01). Mortality 28 days after endotracheal intubation was 28% in patients treated with empirical antibiotics as opposed to 32% in patients treated without (odds ratio: 0.76 [95% CI, 0.61 – 0.94], p&lt;0.01). The administration of empirical antibiotics at intubation in mechanically ventilated COVID-19 patients was associated with a reduced incidence of pulmonary superinfections, a shorter duration of mechanical ventilation and intensive care unit stay, and a lower mortality rate. Notwithstanding these benefits, the applicability of these findings to other viral pneumonias and beyond the pandemic context remains uncertain. Registration: www.clinicaltrials.gov (NCT04457505). [Display omitted] •Emulated targeted trial of 2590 mechanically ventilated COVID-19 patients investigating the effect of empirical antibiotics at intubation.•Empirical antibiotics reduced the incidence of pulmonary superinfections, the duration of mechanical ventilation and the length of intensive care unit stay.•The odds of 28-day mortality were reduced by 24% by empirical antibiotics at intubation, which corresponds to a 4% absolute mortality reduction.•Administering empirical antibiotics when intubating patients with COVID-19 may prevent pulmonary superinfection and lead to improved clinical outcomes.</description><identifier>ISSN: 0163-4453</identifier><identifier>ISSN: 1532-2742</identifier><identifier>EISSN: 1532-2742</identifier><identifier>DOI: 10.1016/j.jinf.2025.106411</identifier><identifier>PMID: 39814268</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Bacterial coinfections ; Bacterial superinfections ; Critically ill ; Prophylactic antibiotics ; Ventilator-associated pneumonia</subject><ispartof>The Journal of infection, 2025-02, Vol.90 (2), p.106411, Article 106411</ispartof><rights>2025 The Authors</rights><rights>Copyright © 2025 The Authors. 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All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1961-fa341a03438ddc5b7a0bbc1ce455e6555106e0ab499779342856ef7d6ae7f8f3</cites><orcidid>0000-0003-3637-3821 ; 0000-0002-9276-3253 ; 0000-0002-2419-3914 ; 0000-0002-0884-5564 ; 0000-0002-7468-4594 ; 0000-0002-2930-0766 ; 0000-0001-9454-062X ; 0000-0002-2299-4849 ; 0000-0003-2240-3532 ; 0000-0002-8331-1554 ; 0000-0002-9149-0310 ; 0000-0001-9946-9703 ; 0000-0002-8817-4683 ; 0000-0003-2722-3979</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39814268$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wendel-Garcia, Pedro D.</creatorcontrib><creatorcontrib>Ceccato, Adrian</creatorcontrib><creatorcontrib>Motos, Ana</creatorcontrib><creatorcontrib>Franch-Llasat, Diego</creatorcontrib><creatorcontrib>Pérez-Moreno, Mar O.</creatorcontrib><creatorcontrib>Domenech-Spanedda, Marie F.</creatorcontrib><creatorcontrib>Chamarro-Martí, Elena</creatorcontrib><creatorcontrib>Ferrer, Ricard</creatorcontrib><creatorcontrib>Fernández-Barat, Laia</creatorcontrib><creatorcontrib>Riera, Jordi</creatorcontrib><creatorcontrib>Álvarez-Napagao, Sergio</creatorcontrib><creatorcontrib>Peñuelas, Oscar</creatorcontrib><creatorcontrib>Lorente, Jose A.</creatorcontrib><creatorcontrib>Almansa, Raquel</creatorcontrib><creatorcontrib>Gabarrús, Albert</creatorcontrib><creatorcontrib>de Gonzalo-Calvo, David</creatorcontrib><creatorcontrib>González, Jessica</creatorcontrib><creatorcontrib>Añon, Jose M.</creatorcontrib><creatorcontrib>Barberà, Carme</creatorcontrib><creatorcontrib>Barberán, José</creatorcontrib><creatorcontrib>Blandino-Ortiz, Aaron</creatorcontrib><creatorcontrib>Bustamante-Munguira, Elena</creatorcontrib><creatorcontrib>Caballero, Jesús</creatorcontrib><creatorcontrib>Carbajales-Pérez, Cristina</creatorcontrib><creatorcontrib>Carbonell, Nieves</creatorcontrib><creatorcontrib>Catalán-González, Mercedes</creatorcontrib><creatorcontrib>Barral-Segade, Patricia</creatorcontrib><creatorcontrib>Mañez, Rafael</creatorcontrib><creatorcontrib>de la Torre, Mari C.</creatorcontrib><creatorcontrib>Díaz, Emili</creatorcontrib><creatorcontrib>Estella, Ángel</creatorcontrib><creatorcontrib>Gallego, Elena</creatorcontrib><creatorcontrib>García-Garmendia, José L.</creatorcontrib><creatorcontrib>Garnacho-Montero, José</creatorcontrib><creatorcontrib>Amaya-Villar, Rosario</creatorcontrib><creatorcontrib>Gómez, José M.</creatorcontrib><creatorcontrib>Huerta, Arturo</creatorcontrib><creatorcontrib>Jorge-García, Ruth N.</creatorcontrib><creatorcontrib>Loza-Vázquez, Ana</creatorcontrib><creatorcontrib>Marin-Corral, Judith</creatorcontrib><creatorcontrib>Martin-Delgado, María Cruz</creatorcontrib><creatorcontrib>de la Gándara, Amalia Martínez</creatorcontrib><creatorcontrib>Martínez-Varela, Ignacio Y.</creatorcontrib><creatorcontrib>López-Messa, Juan</creatorcontrib><creatorcontrib>Muñiz-Albaiceta, Guillermo</creatorcontrib><creatorcontrib>Novo, Mariana A.</creatorcontrib><creatorcontrib>Peñasco, Yhivian</creatorcontrib><creatorcontrib>Pozo-Laderas, Juan C.</creatorcontrib><creatorcontrib>Ricart, Pilar</creatorcontrib><creatorcontrib>Sánchez-Miralles, Ángel</creatorcontrib><creatorcontrib>Sancho, Susana</creatorcontrib><creatorcontrib>Socias, Lorenzo</creatorcontrib><creatorcontrib>Solé-Violan, Jordi</creatorcontrib><creatorcontrib>Suárez-Sipmann, Fernando</creatorcontrib><creatorcontrib>Tamayo, Luis</creatorcontrib><creatorcontrib>Trenado, José</creatorcontrib><creatorcontrib>Barbé, Ferran</creatorcontrib><creatorcontrib>Torres, Antoni</creatorcontrib><creatorcontrib>Roche-Campo, Ferran</creatorcontrib><creatorcontrib>on behalf of the CIBERESUCICOVID Investigators</creatorcontrib><creatorcontrib>CIBERESUCICOVID Investigators</creatorcontrib><title>Empirical antibiotic therapy improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study</title><title>The Journal of infection</title><addtitle>J Infect</addtitle><description>Bacterial pulmonary superinfections develop in a substantial proportion of mechanically ventilated COVID-19 patients and are associated with prolonged mechanical ventilation requirements and increased mortality. Albeit recommended, evidence supporting the use of empirical antibiotics at intubation is weak and of low quality. The aim of this study was to elucidate the effect of empirical antibiotics, administered within 24 h of endotracheal intubation, on superinfections, duration of mechanical ventilation, and mortality in mechanically ventilated patients with COVID-19. Emulated targeted trial by means of a propensity score-matched analysis of a prospective multicentre cohort study of consecutive mechanically ventilated patients admitted to 62 Spanish intensive care units suffering from COVID-19 between March 2020 and February 2021. Overall, 8532 critically ill COVID-19 patients were included, of which 2580 mechanically ventilated patients remained after matching. Empirical antibiotics were prescribed to 1665 (64%) at intubation. Pulmonary superinfections developed in 39% and 47% of patients treated with and without empirical antibiotics, respectively (p&lt;0.01). Patients treated with empirical antibiotics had a shorter duration of mechanical ventilation (incidence risk ratio: 0.85 [95% confidence interval (CI), 0.78 – 0.94], p&lt;0.01) and a reduced stay in the intensive care unit (incidence risk ratio: 0.89 [95% CI, 0.82 – 0.97] days, p&lt;0.01). Mortality 28 days after endotracheal intubation was 28% in patients treated with empirical antibiotics as opposed to 32% in patients treated without (odds ratio: 0.76 [95% CI, 0.61 – 0.94], p&lt;0.01). The administration of empirical antibiotics at intubation in mechanically ventilated COVID-19 patients was associated with a reduced incidence of pulmonary superinfections, a shorter duration of mechanical ventilation and intensive care unit stay, and a lower mortality rate. Notwithstanding these benefits, the applicability of these findings to other viral pneumonias and beyond the pandemic context remains uncertain. Registration: www.clinicaltrials.gov (NCT04457505). 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improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study</title><author>Wendel-Garcia, Pedro D. ; Ceccato, Adrian ; Motos, Ana ; Franch-Llasat, Diego ; Pérez-Moreno, Mar O. ; Domenech-Spanedda, Marie F. ; Chamarro-Martí, Elena ; Ferrer, Ricard ; Fernández-Barat, Laia ; Riera, Jordi ; Álvarez-Napagao, Sergio ; Peñuelas, Oscar ; Lorente, Jose A. ; Almansa, Raquel ; Gabarrús, Albert ; de Gonzalo-Calvo, David ; González, Jessica ; Añon, Jose M. ; Barberà, Carme ; Barberán, José ; Blandino-Ortiz, Aaron ; Bustamante-Munguira, Elena ; Caballero, Jesús ; Carbajales-Pérez, Cristina ; Carbonell, Nieves ; Catalán-González, Mercedes ; Barral-Segade, Patricia ; Mañez, Rafael ; de la Torre, Mari C. ; Díaz, Emili ; Estella, Ángel ; Gallego, Elena ; García-Garmendia, José L. ; Garnacho-Montero, José ; Amaya-Villar, Rosario ; Gómez, José M. ; Huerta, Arturo ; Jorge-García, Ruth N. ; Loza-Vázquez, Ana ; Marin-Corral, Judith ; Martin-Delgado, María Cruz ; de la Gándara, Amalia Martínez ; Martínez-Varela, Ignacio Y. ; López-Messa, Juan ; Muñiz-Albaiceta, Guillermo ; Novo, Mariana A. ; Peñasco, Yhivian ; Pozo-Laderas, Juan C. ; Ricart, Pilar ; Sánchez-Miralles, Ángel ; Sancho, Susana ; Socias, Lorenzo ; Solé-Violan, Jordi ; Suárez-Sipmann, Fernando ; Tamayo, Luis ; Trenado, José ; Barbé, Ferran ; Torres, Antoni ; Roche-Campo, Ferran</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1961-fa341a03438ddc5b7a0bbc1ce455e6555106e0ab499779342856ef7d6ae7f8f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Bacterial coinfections</topic><topic>Bacterial superinfections</topic><topic>Critically ill</topic><topic>Prophylactic antibiotics</topic><topic>Ventilator-associated pneumonia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wendel-Garcia, Pedro D.</creatorcontrib><creatorcontrib>Ceccato, Adrian</creatorcontrib><creatorcontrib>Motos, Ana</creatorcontrib><creatorcontrib>Franch-Llasat, Diego</creatorcontrib><creatorcontrib>Pérez-Moreno, Mar O.</creatorcontrib><creatorcontrib>Domenech-Spanedda, Marie F.</creatorcontrib><creatorcontrib>Chamarro-Martí, Elena</creatorcontrib><creatorcontrib>Ferrer, Ricard</creatorcontrib><creatorcontrib>Fernández-Barat, Laia</creatorcontrib><creatorcontrib>Riera, Jordi</creatorcontrib><creatorcontrib>Álvarez-Napagao, Sergio</creatorcontrib><creatorcontrib>Peñuelas, Oscar</creatorcontrib><creatorcontrib>Lorente, Jose A.</creatorcontrib><creatorcontrib>Almansa, Raquel</creatorcontrib><creatorcontrib>Gabarrús, Albert</creatorcontrib><creatorcontrib>de Gonzalo-Calvo, David</creatorcontrib><creatorcontrib>González, Jessica</creatorcontrib><creatorcontrib>Añon, Jose M.</creatorcontrib><creatorcontrib>Barberà, Carme</creatorcontrib><creatorcontrib>Barberán, 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Ana</creatorcontrib><creatorcontrib>Marin-Corral, Judith</creatorcontrib><creatorcontrib>Martin-Delgado, María Cruz</creatorcontrib><creatorcontrib>de la Gándara, Amalia Martínez</creatorcontrib><creatorcontrib>Martínez-Varela, Ignacio Y.</creatorcontrib><creatorcontrib>López-Messa, Juan</creatorcontrib><creatorcontrib>Muñiz-Albaiceta, Guillermo</creatorcontrib><creatorcontrib>Novo, Mariana A.</creatorcontrib><creatorcontrib>Peñasco, Yhivian</creatorcontrib><creatorcontrib>Pozo-Laderas, Juan C.</creatorcontrib><creatorcontrib>Ricart, Pilar</creatorcontrib><creatorcontrib>Sánchez-Miralles, Ángel</creatorcontrib><creatorcontrib>Sancho, Susana</creatorcontrib><creatorcontrib>Socias, Lorenzo</creatorcontrib><creatorcontrib>Solé-Violan, Jordi</creatorcontrib><creatorcontrib>Suárez-Sipmann, Fernando</creatorcontrib><creatorcontrib>Tamayo, Luis</creatorcontrib><creatorcontrib>Trenado, José</creatorcontrib><creatorcontrib>Barbé, Ferran</creatorcontrib><creatorcontrib>Torres, Antoni</creatorcontrib><creatorcontrib>Roche-Campo, Ferran</creatorcontrib><creatorcontrib>on behalf of the CIBERESUCICOVID Investigators</creatorcontrib><creatorcontrib>CIBERESUCICOVID Investigators</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of infection</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wendel-Garcia, Pedro D.</au><au>Ceccato, Adrian</au><au>Motos, Ana</au><au>Franch-Llasat, Diego</au><au>Pérez-Moreno, Mar O.</au><au>Domenech-Spanedda, Marie F.</au><au>Chamarro-Martí, Elena</au><au>Ferrer, Ricard</au><au>Fernández-Barat, Laia</au><au>Riera, Jordi</au><au>Álvarez-Napagao, Sergio</au><au>Peñuelas, Oscar</au><au>Lorente, Jose A.</au><au>Almansa, Raquel</au><au>Gabarrús, Albert</au><au>de Gonzalo-Calvo, David</au><au>González, Jessica</au><au>Añon, Jose M.</au><au>Barberà, Carme</au><au>Barberán, José</au><au>Blandino-Ortiz, Aaron</au><au>Bustamante-Munguira, Elena</au><au>Caballero, Jesús</au><au>Carbajales-Pérez, Cristina</au><au>Carbonell, Nieves</au><au>Catalán-González, Mercedes</au><au>Barral-Segade, Patricia</au><au>Mañez, Rafael</au><au>de la Torre, Mari C.</au><au>Díaz, Emili</au><au>Estella, Ángel</au><au>Gallego, Elena</au><au>García-Garmendia, José L.</au><au>Garnacho-Montero, José</au><au>Amaya-Villar, Rosario</au><au>Gómez, José M.</au><au>Huerta, Arturo</au><au>Jorge-García, Ruth N.</au><au>Loza-Vázquez, Ana</au><au>Marin-Corral, Judith</au><au>Martin-Delgado, María Cruz</au><au>de la Gándara, Amalia Martínez</au><au>Martínez-Varela, Ignacio Y.</au><au>López-Messa, Juan</au><au>Muñiz-Albaiceta, Guillermo</au><au>Novo, Mariana A.</au><au>Peñasco, Yhivian</au><au>Pozo-Laderas, Juan C.</au><au>Ricart, Pilar</au><au>Sánchez-Miralles, Ángel</au><au>Sancho, Susana</au><au>Socias, Lorenzo</au><au>Solé-Violan, Jordi</au><au>Suárez-Sipmann, Fernando</au><au>Tamayo, Luis</au><au>Trenado, José</au><au>Barbé, Ferran</au><au>Torres, Antoni</au><au>Roche-Campo, Ferran</au><aucorp>on behalf of the CIBERESUCICOVID Investigators</aucorp><aucorp>CIBERESUCICOVID Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Empirical antibiotic therapy improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study</atitle><jtitle>The Journal of infection</jtitle><addtitle>J Infect</addtitle><date>2025-02</date><risdate>2025</risdate><volume>90</volume><issue>2</issue><spage>106411</spage><pages>106411-</pages><artnum>106411</artnum><issn>0163-4453</issn><issn>1532-2742</issn><eissn>1532-2742</eissn><abstract>Bacterial pulmonary superinfections develop in a substantial proportion of mechanically ventilated COVID-19 patients and are associated with prolonged mechanical ventilation requirements and increased mortality. Albeit recommended, evidence supporting the use of empirical antibiotics at intubation is weak and of low quality. The aim of this study was to elucidate the effect of empirical antibiotics, administered within 24 h of endotracheal intubation, on superinfections, duration of mechanical ventilation, and mortality in mechanically ventilated patients with COVID-19. Emulated targeted trial by means of a propensity score-matched analysis of a prospective multicentre cohort study of consecutive mechanically ventilated patients admitted to 62 Spanish intensive care units suffering from COVID-19 between March 2020 and February 2021. Overall, 8532 critically ill COVID-19 patients were included, of which 2580 mechanically ventilated patients remained after matching. Empirical antibiotics were prescribed to 1665 (64%) at intubation. Pulmonary superinfections developed in 39% and 47% of patients treated with and without empirical antibiotics, respectively (p&lt;0.01). Patients treated with empirical antibiotics had a shorter duration of mechanical ventilation (incidence risk ratio: 0.85 [95% confidence interval (CI), 0.78 – 0.94], p&lt;0.01) and a reduced stay in the intensive care unit (incidence risk ratio: 0.89 [95% CI, 0.82 – 0.97] days, p&lt;0.01). Mortality 28 days after endotracheal intubation was 28% in patients treated with empirical antibiotics as opposed to 32% in patients treated without (odds ratio: 0.76 [95% CI, 0.61 – 0.94], p&lt;0.01). The administration of empirical antibiotics at intubation in mechanically ventilated COVID-19 patients was associated with a reduced incidence of pulmonary superinfections, a shorter duration of mechanical ventilation and intensive care unit stay, and a lower mortality rate. Notwithstanding these benefits, the applicability of these findings to other viral pneumonias and beyond the pandemic context remains uncertain. Registration: www.clinicaltrials.gov (NCT04457505). [Display omitted] •Emulated targeted trial of 2590 mechanically ventilated COVID-19 patients investigating the effect of empirical antibiotics at intubation.•Empirical antibiotics reduced the incidence of pulmonary superinfections, the duration of mechanical ventilation and the length of intensive care unit stay.•The odds of 28-day mortality were reduced by 24% by empirical antibiotics at intubation, which corresponds to a 4% absolute mortality reduction.•Administering empirical antibiotics when intubating patients with COVID-19 may prevent pulmonary superinfection and lead to improved clinical outcomes.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>39814268</pmid><doi>10.1016/j.jinf.2025.106411</doi><orcidid>https://orcid.org/0000-0003-3637-3821</orcidid><orcidid>https://orcid.org/0000-0002-9276-3253</orcidid><orcidid>https://orcid.org/0000-0002-2419-3914</orcidid><orcidid>https://orcid.org/0000-0002-0884-5564</orcidid><orcidid>https://orcid.org/0000-0002-7468-4594</orcidid><orcidid>https://orcid.org/0000-0002-2930-0766</orcidid><orcidid>https://orcid.org/0000-0001-9454-062X</orcidid><orcidid>https://orcid.org/0000-0002-2299-4849</orcidid><orcidid>https://orcid.org/0000-0003-2240-3532</orcidid><orcidid>https://orcid.org/0000-0002-8331-1554</orcidid><orcidid>https://orcid.org/0000-0002-9149-0310</orcidid><orcidid>https://orcid.org/0000-0001-9946-9703</orcidid><orcidid>https://orcid.org/0000-0002-8817-4683</orcidid><orcidid>https://orcid.org/0000-0003-2722-3979</orcidid><oa>free_for_read</oa></addata></record>
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subjects Bacterial coinfections
Bacterial superinfections
Critically ill
Prophylactic antibiotics
Ventilator-associated pneumonia
title Empirical antibiotic therapy improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study
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