Early bacterial co-infections and ventilator-associated lower respiratory tract infections among intubated patients during the first and second COVID-19 waves: a European comparative cohort study.

Background: The management of severe SARS-CoV-2 pneumonia, alongside logistical constraints, evolved between the first and subsequent COVID-19 waves. This study aimed to compare the prevalence of early bacterial pulmonary co-infections and the incidence of ventilator-associated lower respiratory tract infections (VA-LRTI) across the first and second waves of the pandemic, and to characterize their microbiology.

Methods: Latter part of a multicenter retrospective European cohort analysis conducted in 35 ICUs. Adult patients admitted for SARS-CoV-2 pneumonia and requiring invasive mechanical ventilation ≥ 48 h were consecutively included from both waves (February-May 2020 for period 1, October 2020-April 2021 for period 2). Co-infections were defined by bacterial isolation in respiratory secretions or blood cultures, or a positive pneumococcal urinary antigen test, within 48 h after intubation. VA-LRTI, including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP), were diagnosed using clinical, radiological and quantitative microbiological criteria. The 28-day cumulative incidence of first VA-LRTI episodes was estimated using the Kalbfleisch and Prentice method, with co-infection prevalence and VA-LRTI incidence compared using multivariable logistic regression and Fine-and-Gray models, respectively.

Results: The study included 1,154 patients (558 in period 1 and 596 in period 2). Co-infection prevalence significantly rose from 9.7% in period 1 to 14.9% in period 2 (adjusted odds ratio (95% confidence interval) 1.52 (1.04-2.22), p = 0.03). Gram-positive cocci dropped from 59 to 48% of co-infections between periods 1 and 2. The overall incidence of VA-LRTI was similar across periods (50.4% and 53.9%, adjusted sub distribution hazard ratio (sHR) 1.14 (0.96-1.35), p = 0.11), with a significant increase in VAP incidence in period 2 (36% to 44.8%, adjusted sHR 1.37 (1.12-1.66), p = 0.001), predominantly occurring within the initial 14 days after intubation, and a concurrent significant decrease in VAT incidence (14.3% to 9.1%, adjusted sHR 0.61 (0.42-0.88), p = 0.007). Gram-negative bacilli, led by Pseudomonas aeruginosa, Enterobacter spp., and Klebsiella spp., were responsible for 89% and 84% of VA-LRTI in periods 1 and 2, respectively.

Conclusions: Between the first and second COVID-19 waves, the prevalence of early bacterial pulmonary co-infections significantly increased among intubated patients. Although the overall incidence of VA-LRTI remained stable, there was a significant shift from VAT to VAP episodes.