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 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