Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19: a multinational, multicentre study, prospective, observational study

Abstract

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40-2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98-1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes.Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable. © 2023. The Author(s).

Alrededor de un tercio de los pacientes diagnosticados con COVID-19 desarrollan una enfermedad grave que requiere ingreso en la Unidad de Cuidados Intensivos (UCI). En la práctica clínica, los médicos han aprendido que los pacientes ingresados ​​en la UCI debido a COVID-19 grave con frecuencia desarrollan infecciones del tracto respiratorio inferior asociadas al ventilador (VA-LRTI). Este estudio tiene como objetivo describir las características clínicas, los factores asociados con VA-LRTI y su impacto en los resultados clínicos en pacientes con COVID-19 grave. Se trata de un estudio de cohorte observacional multicéntrico realizado en diez países de América Latina y Europa. Incluimos pacientes con rtPCR confirmada para SARS-CoV-2 que requirieron ingreso en UCI e intubación endotraqueal. Sólo se incluyeron pacientes con diagnóstico microbiológico y clínico de VA-LRTI. Se realizaron análisis de regresión logística multivariada y Random Forest para determinar los factores de riesgo de VA-LRTI y su impacto clínico en pacientes con COVID-19 grave. En nuestra cohorte de estudio de 3287 pacientes, se diagnosticó VA-LRTI en el 28,8% [948/3287]. La incidencia acumulada de neumonía asociada a ventilación (NAV) fue del 18,6% [610/3287], seguida de traqueobronquitis asociada a ventilación (VAT) del 10,3% [338/3287]. Se aislaron un total de 1252 especies de bacterias. Los patógenos aislados con mayor frecuencia fueron Pseudomonas aeruginosa (21,2% [266/1252]), seguido de Klebsiella pneumoniae (19,1% [239/1252]) y Staphylococcus aureus (15,5% [194/1252]). Los factores asociados de forma independiente con el desarrollo de VA-LRTI fueron la estancia prolongada bajo ventilación mecánica invasiva, la IRA durante la estancia en la UCI y el número de comorbilidades. En cuanto al impacto clínico de VA-LRTI, los pacientes con VAP tuvieron un mayor riesgo de mortalidad hospitalaria (OR [IC 95%] de 1,81 [1,40-2,34]), mientras que VAT no se asoció con un aumento de mortalidad hospitalaria (OR [IC 95%] ] de 1,34 [0,98-1,83]).