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The clinical criteria did not distinguish between patients with or without bacterial superinfection. 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. Bacterial superinfection within 48 hours of intubation was detected in 21% of patients. Measurements and Main Results: We analyzed 386 BAL samples from 179 patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. Actual antibiotic use was compared with guideline-recommended therapy. 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. 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. Rates of ventilator-associated pneumonia (VAP) in clinical trials of patients with SARS-CoV-2 pneumonia are unexpectedly low. 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. A Christine Argento, Ajay A Wagh, Alexander V Misharin, Alexandra C McQuattie-Pimentel, Alexis Rose Wolfe, Alvaro Donayre, Ankit Bharat, Anne R Levenson, Anthony M Joudi, Betty Tran, Chitaru Kurihara, Clara J Schroedl, Daniel Meza, Daniel Schneider, David A Kidd, David D Odell, David W Kamp, Elizabeth S Malsin, Emily M Leibenguth, Eric P Cantey, Gabrielle Y Liu, Helen K Donnelly, Isaac A Goldberg, Jacob I Sznajder, Jacqueline M Kruser, James M Walter, Jane E Dematte, John Coleman, Joseph I Bailey, Joseph S Deters, Justin A Fiala, Katharine Secunda, Kaitlyn Vitale, Khalilah L Gates, Kristy Todd, Lindsey D Gradone, Lindsey N Textor, Lisa F Wolfe, Madeline L Rosenbaum, Manu Jain, Marc A Sala, Mary Carns, Marysa V Leya, Michael J Alexander, Michelle Hinsch Prickett, Natalie Jensema, Nicole Borkowski, Nikolay S Markov, Orlyn R Rivas, Paul A Reyfman, Peter H S Sporn, Prasanth Nannapaneni, Rachel B Kadar, Rachel M Kaplan, Rade Tomic, Radhika Patel, Rafael Garza-Castillon, Ravi Kalhan, Romy Lawrence, Ruben J Mylvaganam, Samuel S Kim, Sanket Thakkar, SeungHye Han, Sharon R Rosenberg, Susan R Russell, Sydney M Hyder, Taylor A Poor, Theresa A Lombardo, Zasu M Klug