Bacterial Superinfection Pneumonia in Patients Mechanically Ventilated for COVID-19 Pneumonia

Abstract

Rationale: Current guidelines recommend patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia receive empirical antibiotics for suspected bacterial superinfection on the basis of weak evidence. Rates of ventilator-associated pneumonia (VAP) in clinical trials of patients with SARS-CoV-2 pneumonia are unexpectedly low. Objectives: We conducted an observational single-center study to determine the prevalence and etiology of bacterial superinfection at the time of initial intubation and the incidence and etiology of subsequent bacterial VAP in patients with severe SARS-CoV-2 pneumonia. Methods: Bronchoscopic BAL fluid samples from all patients with SARS-CoV-2 pneumonia requiring mechanical ventilation were analyzed using quantitative cultures and a multiplex PCR panel. Actual antibiotic use was compared with guideline-recommended therapy. Measurements and Main Results: We analyzed 386 BAL samples from 179 patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. Bacterial superinfection within 48 hours of intubation was detected in 21% of patients. Seventy-two patients (44.4%) developed at least one VAP episode (VAP incidence rate = 45.2/1,000 ventilator days); 15 (20.8%) initial VAPs were caused by difficult-to-treat pathogens. The clinical criteria did not distinguish between patients with or without bacterial superinfection. BAL-based management was associated with significantly reduced antibiotic use compared with guideline recommendations. Conclusions: In patients with SARS-CoV-2 pneumonia requiring mechanical ventilation, bacterial superinfection at the time of intubation occurs in <25% of patients. Guideline-based empirical antibiotic management at the time of intubation results in antibiotic overuse. Bacterial VAP developed in 44% of patients and could not be accurately identified in the absence of microbiologic analysis of BAL fluid.

Keywords: COVID-19; bronchoalveolar lavage; community-acquired pneumonia; guideline therapy; ventilator-associated pneumonia.

Figure 1.

Median NAT score in response to BAL results overall and in response to positive and negative BAL results for patients undergoing bronchoscopy within 48 hours of intubation. A score of −2 indicates no antibiotic therapy, and a score of 0 corresponds to guideline-recommended treatment for patients with severe community-acquired pneumonia. NAT = narrow antibiotic therapy.

Figure 2.

(A and B) BAL results for suspected VAP (A) and pathogens detected in positive BAL results (B). Dark bars are pathogens detected in monomicrobial episodes, whereas lighter bars are presence in polymicrobial pneumonias. E. coli = Escherichia coli; H. influenzae = Haemophilus influenzae; K. aerogenes = Klebsiella aerogenes; K. pneumoniae = Klebsiella pneumoniae; MRSA = methicillin-resistant S. aureus; MSSA = methicillin-susceptible S. aureus; P. aeruginosa = Pseudomonas aeruginosa; S. aureus = Staphylococcus aureus; S. marcescens = Serratia marcescens; VAP = ventilator-associated pneumonia.

Figure 3.

(A) Cumulative ventilator-associated pneumonias (VAPs) by etiology and resistance pattern. For Enterobacterales, resistant isolates were defined as requiring carbapenem or broader spectrum β-lactam treatment. (B) Incidence of VAP. Cumulative new VAP diagnoses per cumulative ventilator days. Individual patients can have more than one VAP episode. H. influenzae = Haemophilus influenzae; MRSA = methicillin-resistant Staphylococcus aureus; MSSA = methicillin-susceptible Staphylococcus aureus.