Empirical antibiotic therapy improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study - 13/02/25

Doi : 10.1016/j.jinf.2025.106411

Pedro D. Wendel-Garcia ^a,^b,^⁎ , Adrian Ceccato ^c,^d,^e, Ana Motos ^c,^f, Diego Franch-Llasat ^g, Mar O. Pérez-Moreno ^h, Marie F. Domenech-Spanedda ⁱ, Elena Chamarro-Martí ^j, Ricard Ferrer ^k, Laia Fernández-Barat ^c,^f, Jordi Riera ^k, Sergio Álvarez-Napagao ^l, Oscar Peñuelas ^c,^m, Jose A. Lorente ^c,^m, Raquel Almansa ⁿ, Albert Gabarrús ^f, David de Gonzalo-Calvo ^c,^o, Jessica González ^c,^p, Jose M. Añon ^c,^q, Carme Barberà ^r, José Barberán ^s, Aaron Blandino-Ortiz ^t, Elena Bustamante-Munguira ^u, Jesús Caballero ^v, Cristina Carbajales-Pérez ^w, Nieves Carbonell ^x, Mercedes Catalán-González ^y, Patricia Barral-Segade ^z, Rafael Mañez ^aa, Mari C. de la Torre ^ab, Emili Díaz ^ac,^ad, Ángel Estella ^ae, Elena Gallego ^af, José L. García-Garmendia ^ag, José Garnacho-Montero ^ah, Rosario Amaya-Villar ^ai, José M. Gómez ^aj, Arturo Huerta ^ak, Ruth N. Jorge-García ^al, Ana Loza-Vázquez ^am, Judith Marin-Corral ^an, María Cruz Martin-Delgado ^ao, Amalia Martínez de la Gándara ^ap, Ignacio Y. Martínez-Varela ^aq, Juan López-Messa ^ar, Guillermo Muñiz-Albaiceta ^c,^as, Mariana A. Novo ^at, Yhivian Peñasco ^au, Juan C. Pozo-Laderas ^av, Pilar Ricart ^aw, Ángel Sánchez-Miralles ^ax, Susana Sancho ^ay, Lorenzo Socias ^az, Jordi Solé-Violan ^ba, Fernando Suárez-Sipmann ^bb, Luis Tamayo ^bc, José Trenado ^bd, Ferran Barbé ^c,^p, Antoni Torres ^c,^f,^{^{1
Antoni Torres and Ferran Roche-Campo contributed equally as senior authors.}}, Ferran Roche-Campo ^g,^{^{1
Antoni Torres and Ferran Roche-Campo contributed equally as senior authors.}}
on behalf of the CIBERESUCICOVID Investigators^²
A complete list of the CIBERESUCICOVID Investigators may be found in the online supplement.
^a Institute of Intensive Care Medicine, University Hospital Zurich, Zurich, Switzerland
^b Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care Medicine, Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria
^c CIBER of Respiratory Diseases (CIBERES), Institute of Health Carlos III, Madrid, Spain
^d Intensive Care Unit, University Hospital Sagrat Cor, Quironsalud Group, Barcelona, Spain
^e Critical Care Center, University Hospital Parc Taulí, Institute of Research and Innovation Parc Taulí (I3PT), Sabadell, Spain
^f Department of Pneumology, Hospital Clinic, Barcelona, Spain
^g Department of Critical Care Medicine, Hospital Verge de la Cinta, Tortosa, Pere Virgili Institute for Health Research, Spain
^h Department of Clinical Laboratory Medicine, Hospital Verge de la Cinta, Tortosa, Pere Virgili Institute for Health Research, Spain
ⁱ Department of Preventive Medicine, Hospital Verge de la Cinta, Tortosa, Pere Virgili Institute for Health Research, Spain
^j Department of Internal Medicine, Hospital Verge de la Cinta, Tortosa, Pere Virgili Institute for Health Research, Spain
^k Intensive Care Department, SODIR-VHIR Research Group, Vall d’Hebron University Hospital, Barcelona, Spain
^l Barcelona Supercomputing Centre (BSC), Barcelona, Spain
^m Department of Critical Care Medicine, University Hospital of Getafe, Madrid, Spain
ⁿ Group for Biomedical Research in Sepsis (BioSepsis), Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
^o Translational Research in Respiratory Medicine, University Hospital Arnau de Vilanova and Santa Maria, IRB Lleida, Lleida, Spain
^p Department of Pneumology, University Hospital Arnau de Vilanova and Santa Maria, Lleida, Spain
^q Department of Critical Care Medicine, University Hospital La Paz, IdiPAZ, Madrid, Spain
^r Department of Critical Care Medicine, Hospital Santa Maria, Lleida, Spain
^s Department of Internal Medicine, University Hospital HM Montepríncipe, Madrid, Spain
^t Department of Critical Care Medicine, University Hospital Ramón y Cajal, Madrid, Spain
^u Department of Critical Care Medicine, University Hospital Valladolid, Valladolid, Spain
^v Department of Critical Care Medicine, University Hospital Arnau de Vilanova and Santa Maria, Lleida, Spain
^w Department of Critical Care Medicine, Hospital Álvaro Cunqueiro, Vigo, Spain
^x Department of Critical Care Medicine, University Clinic Hospital of Valencia, Valencia, Spain
^y Department of Critical Care Medicine, University Hospital 12 de Octubre, Madrid, Spain
^z Department of Critical Care Medicine, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
^aa Department of Critical Care Medicine, Bellvitge University Hospital, L’Hospitalet de Llobregat, Spain
^ab Department of Critical Care Medicine, Mataró Hospital, Barcelona, Spain
^ac Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain
^ad Department of Critical Care Medicine, Healthcare Corporation Parc Taulí, Sabadell, Spain
^ae Department and Faculty of Medicine, University Hospital of Jerez, Jerez de la Frontera, Spain
^af Department of Critical Care Medicine, University Hospital San Pedro de Alcántara, Cáceres, Spain
^ag Department of Critical Care Medicine, Hospital San Juan de Dios del Aljarafe, Sevilla, Spain
^ah Department of Critical Care Medicine, University Hospital Virgen Macarena, Sevilla, Spain
^ai Department of Critical Care Medicine, University Hospital Virgen del Rocio, Sevilla, Spain
^aj Department of Critical Care Medicine, University Hospital Gregorio Marañón, Madrid, Spain
^ak Pulmonary and Critical Care Division, Sagrada Família Clinic, Barcelona, Spain
^al Department of Critical Care Medicine, Hospital Nuestra Señora de Gracia, Zaragoza, Spain
^am Department of Critical Care Medicine, University Hospital Virgen de Valme, Sevilla, Spain
^an Department of Critical Care Medicine, Hospital del Mar, Barcelona, Spain
^ao Department of Critical Care Medicine, University Hospital of Torrejón, Madrid, Spain
^ap Department of Critical Care Medicine, University Hosptial Infanta Leonor, Madrid, Spain
^aq Department of Critical Care Medicine, University Hospital Lucus Augusti, Lugo, Spain
^ar Department of Critical Care Medicine, University Hospital of Palencia, Palencia, Spain
^as Department of Functional Biology, Central Hospital of Asturias, Oviedo, Spain
^at Department of Critical Care Medicine, University Hospital Son Espases, Palma de Mallorca, Spain
^au Department of Critical Care Medicine, University Hospital Marqués de Valdecilla, Santander, Spain
^av Department of Critical Care Medicine, University Hospital Reina Sofia, Córdoba, Spain
^aw Department of Critical Care Medicine, University Hospital Germans Trias, Badalona, Spain
^ax Department of Critical Care Medicine, Hospital of Sant Joan d’Alacant, Alicante, Spain
^ay Department of Critical Care Medicine, University and Polytechnic Hospital La Fe, Valencia, Spain
^az Department of Critical Care Medicine, Hospital Son Llàtzer, Palma de Mallorca, Spain
^ba Department of Critical Care Medicine, University Hospital Dr. Negrín, University Fernando Pessoa-Canarias, Las Palmas de Gran Canaria, Spain
^bb Department of Critical Care Medicine, University Hospital La Princesa, Madrid, Spain
^bc Department of Critical Care Medicine, University Hospital Río Hortega, Valladolid, Spain
^bd Department of Critical Care Medicine, University Hospital Mútua Terrassa, Terrassa, Spain

^⁎Correspondence to: Institute of Intensive Care Medicine, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.Institute of Intensive Care Medicine, University Hospital ZurichRämistrasse 100Zurich8091Switzerland

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Summary

Background

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.

Methods

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.

Results

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<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<0.01) and a reduced stay in the intensive care unit (incidence risk ratio: 0.89 [95% CI, 0.82 – 0.97] days, p<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<0.01).

Conclusion

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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Graphical Abstract

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Highlights

•	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.

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Keywords : Prophylactic antibiotics, Bacterial superinfections, Bacterial coinfections, Ventilator-associated pneumonia, Critically ill

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Vol 90 - N° 2

Article 106411- février 2025 Retour au numéro

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Empirical antibiotic therapy improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study - 13/02/25

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