Bacterial pulmonary superinfections are associated with longer duration of ventilation in critically ill COVID-19 patients

Abstract

The impact of secondary bacterial infections (superinfections) in coronavirus disease 2019 (COVID-19) is not well understood. In this prospective, monocentric cohort study, we aim to investigate the impact of superinfections in COVID-19 patients with acute respiratory distress syndrome. Patients are assessed for concomitant microbial infections by longitudinal analysis of tracheobronchial secretions, bronchoalveolar lavages, and blood cultures. In 45 critically ill patients, we identify 19 patients with superinfections (42.2%). Superinfections are detected on day 10 after intensive care admission. The proportion of participants alive and off invasive mechanical ventilation at study day 28 (ventilator-free days [VFDs] at 28 days) is substantially lower in patients with superinfection (subhazard ratio 0.37; 95% confidence interval [CI] 0.15-0.90; p = 0.028). Patients with pulmonary superinfections have a higher incidence of bacteremia, virus reactivations, yeast colonization, and required intensive care treatment for a longer time. Superinfections are frequent and associated with reduced VFDs at 28 days despite a high rate of empirical antibiotic therapy.

Keywords: ARDS; COVID-19; SARS-CoV-2; acute respiratory distress syndrome; antibiotic therapy; bacterial superinfection; co-infection; coronavirus disease 19; invasive mechanical ventilation; longitudinal sampling; severe acute respiratory syndrome coronavirus 2; ventilator free at 28 days.

Graphical abstract

Figure 1

Spectrum and isolation time points in TBSs and BALs reflect hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) spectrum (A) First detection time points of the most frequently cultured respiratory pathogens censored at 42 days (detection of Acinetobacter baumannii at day 77 and A. bereziniae at day 66). The n refers to the number of patients with a first detection of the respective pathogen. A total of 468 respiratory specimens from 45 patients were analyzed. Only the first detection event of a relevant respiratory pathogen in a given patient is reported. (B) Antibiotics used for treatment of superinfections. (C) Empiric antibiotic therapy used during first course of antibiotic treatment (before or at admission onto ICU). See also Figures S1 and S2.

Figure 2

Proportion of participants alive and off invasive mechanical ventilation at study day 28 (ventilator-free days [VFDs] at 28 days) Cumulative incidence curves for proportion of participants alive and off invasive mechanical ventilation at study day 28 (VFDs at 28 days). Only patients receiving invasive mechanical ventilation (N = 40) were included in this analysis. See also Figure S3 and Table S1.