Early Bacterial Identification among Intubated Patients with COVID-19 or Influenza Pneumonia: A European Multicenter Comparative Clinical Trial

Abstract

Rationale: Early empirical antimicrobial treatment is frequently prescribed to critically ill patients with coronavirus disease (COVID-19) based on Surviving Sepsis Campaign guidelines.Objectives: We aimed to determine the prevalence of early bacterial identification in intubated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, as compared with influenza pneumonia, and to characterize its microbiology and impact on outcomes.Methods: A multicenter retrospective European cohort was performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation >48 hours were eligible if they had SARS-CoV-2 or influenza pneumonia at ICU admission. Bacterial identification was defined by a positive bacterial culture within 48 hours after intubation in endotracheal aspirates, BAL, blood cultures, or a positive pneumococcal or legionella urinary antigen test.Measurements and Main Results: A total of 1,050 patients were included (568 in SARS-CoV-2 and 482 in influenza groups). The prevalence of bacterial identification was significantly lower in patients with SARS-CoV-2 pneumonia compared with patients with influenza pneumonia (9.7 vs. 33.6%; unadjusted odds ratio, 0.21; 95% confidence interval [CI], 0.15-0.30; adjusted odds ratio, 0.23; 95% CI, 0.16-0.33; P < 0.0001). Gram-positive cocci were responsible for 58% and 72% of coinfection in patients with SARS-CoV-2 and influenza pneumonia, respectively. Bacterial identification was associated with increased adjusted hazard ratio for 28-day mortality in patients with SARS-CoV-2 pneumonia (1.57; 95% CI, 1.01-2.44; P = 0.043). However, no significant difference was found in the heterogeneity of outcomes related to bacterial identification between the two study groups, suggesting that the impact of coinfection on mortality was not different between patients with SARS-CoV-2 and influenza.Conclusions: Bacterial identification within 48 hours after intubation is significantly less frequent in patients with SARS-CoV-2 pneumonia than patients with influenza pneumonia.Clinical trial registered with www.clinicaltrials.gov (NCT04359693).

Keywords: SARS-CoV-2; bacterial; influenza; intensive care; mechanical ventilation.

Figure 1.

Patient flowchart. SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

Figure 2.

Cumulative incidence of (A) 28-day mortality, (B) extubation alive, and (C) and ICU discharge alive according to study groups (SARS-CoV-2 pneumonia vs. influenza pneumonia) and early bacterial identification. Time axis origin is the day of intubation. SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

Figure 3.

Association of early bacterial identification with 28-day outcomes according to study groups (SARS-CoV-2 pneumonia and influenza pneumonia). HRs were calculated using cause-specific proportional hazard models by considering mortality as a competing event for mechanical ventilation and length of ICU stay. Adjusted HRs were calculated by including sex, simplified acute physiology score II, body mass index, MacCabe classification, shock, acute respiratory distress syndrome, cardiac arrest, antibiotic treatment on ICU admission, and ventilator-associated pneumonia (treated as time-varying variable) as prespecified covariates in Cox’s models (after handling missing values by multiple imputation). An HR > 1 indicates a decrease in survival (i.e., an increased risk for mortality), MV duration (i.e., an increased risk for extubation alive), and ICU length of stay (i.e., an increased risk for discharge alive), and an HR < 1 indicates an increase in survival (i.e., a decreased risk for mortality), MV duration (i.e., a decreased risk for extubation alive), and ICU length of stay (i.e., a decreased risk for discharge alive). The event of interest for survival is a pejorative event (death), whereas for MV duration and ICU length of stay, the event of interest is a positive event (extubation or discharge alive). Consequently, the detrimental effect of bacterial identification on each outcome was associated with an HR > 1 for overall survival but with an HR < 1 for MV duration and ICU length of stay. P Het indicates the P value for heterogeneity in association of bacterial identification and 28-day outcomes across study groups (SARS-CoV-2 pneumonia vs. influenza pneumonia). CI = confidence interval; HR = hazard ratio; MV = mechanical ventilation; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.