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

• DOI: 10.1016/j.jinf.2025.106411
• Publication Date: 2025-01-14T00:10:50Z
• Authors: Pedro D. Wendel-G...; Adrian Ceccato; Ana Motos; Diego Franch-Llasat; Mar O. Pérez-Moreno; Marie F. Domenech...; Elena Chamarro-Martí; Ricard Ferrer; Laia Fernández-Barat; Jordi Riera; Sergio Álvarez-Na...; Oscar Peñuelas; Jose A. Lorente; Raquel Almansa; Albert Gabarrús; David de Gonzalo-...; Jessica González; Jose M. Añon; Carme Barberà; José Barberán; Aaron Blandino-Ortiz; Elena Bustamante-...; Jesús Caballero; Cristina Carbajal...; Nieves Carbonell; Mercedes Catalán-...; Patricia Barral-S...; Rafael Mañez; Mari C. de la Torre; Emili Díaz; Ángel Estella; Elena Gallego; José L. García-Ga...; José Garnacho-Mon...; Rosario Amaya-Villar; José M. Gómez; Arturo Huerta; Ruth N. Jorge-García; Ana Loza-Vázquez; Judith Marin-Corral; María Cruz Martin...; Amalia Martínez d...; Ignacio Y. Martín...; Juan López-Messa; Guillermo Muñiz-A...; Mariana A. Novo; Yhivian Peñasco; Juan C. Pozo-Laderas; Pilar Ricart; Ángel Sánchez-Mir...; Susana Sancho; Lorenzo Socias; Jordi Solé-Violan; Fernando Suárez-S...; Luis Tamayo; José Trenado; Ferran Barbé; Antoni Torres; Ferran Roche-Campo
• Keywords: 2019-20 coronavirus outbreak; Antibiotic Therapy; Rescue therapy

Bacterial pulmonary superinfections develop in a substantial proportion of mechanically ventilated COVID-19 patients and are associated with prolonged mechanical ventilation requirements and an 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 24hours 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, 8,532 critically-ill COVID-19 patients were included, of which 2,580 mechanically ventilated patients remained after matching. Empirical antibiotics were prescribed to 1,665 (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). 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. www. gov (NCT04457505).