Predictors of hospital-acquired bacterial and fungal superinfections in COVID-19: a prospective observational study

Falcone, M; Tiseo, G; Giordano, C; Leonildi, A; Menichini, M; Vecchione, A; Pistello, M; Guarracino, F; Ghiadoni, L; Forfori, F; Barnini, S; Menichetti, F; on behalf of the Pisa COVID-19 Study Group: Sabrina Agostini, O Degl’Innocenti; Barbieri, Greta; Biancalana, Martina; Borselli, Matteo; Elia Nencini and Stefano Spinelli (Emergency Medicine Unit,; Azienda Ospedaliero Universitaria Pisana),; Antognoli, Rachele; Calsolario, Valeria; Fabio Monzani and Simone Paterni (Geriatrics Unit,; Azienda Ospedaliero Universitaria Pisana),; Baldassarri, Rubia; Bertini, Pietro; Brizzi, Giulia; Alessandra Della Rocca,; Malacarne, Paolo; Marco Monfroni and Chiara Piagnani (Department of Anaesthesia and Intensive Care,; Azienda Ospedaliero Universitaria Pisana),; Carpene`, Nicoletta; Carrozzi, Laura; Celi, Alessandro; Desideri, Massimiliano; Marco Gherardi and Massimiliano Serradori (Respiratory Unit,; Azienda Ospedaliero Universitaria Pisana),; Cinotti, Francesco; Alessandro Cipriano and Naria Park (Emergency Department,; Azienda Ospedaliero Universitaria Pisana),; Forotti, Giovanna; Mengozzi, Alessandro; Masi, Stefano; Ruberti, Francesca; Maria Sciuto and Agostino Virdis (Internal Medicine Department,; Azienda Ospedaliero Universitaria Pisana),; Fabrizio Maggi (Virology Unit, Department of Laboratory Medicine Pisa University Hospital); and Valentina Galfo (Infectious Disease Unit,; Department of Clinical and Experimental Medicine,; University of, Pisa).

doi:10.1093/jac/dkaa530

Background: Bacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19. Objectives: To identify predictors of superinfections in COVID-19. Methods: Prospective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred 48 h after hospital admission. Amultivariate analysis was performed to identify factors independently associated with superinfections. Results: Overall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11–29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfections were: intestinal colonization by carbapenem-resistant Enterobacterales (OR 16.03, 95% CI 6.5–39.5, P < 0.001); invasive mechanical ventilation (OR 5.6, 95% CI 2.4–13.1, P < 0.001); immunomodulatory agents (tocilizumab/baricitinib) (OR 5.09, 95% CI 2.2–11.8, P < 0.001); C-reactive protein on admission >7 mg/dl (OR 3.59, 95% CI 1.7–7.7, P = 0.001); and previous treatment with piperacillin/tazobactam (OR 2.85, 95% CI 1.1–7.2, P = 0.028). Length of hospital stay was longer in patients who developed superinfections ompared with those who did not (30 versus 11 days, P < 0.001), while mortality rates were similar (18.8% versus 23.2%, P = 0.445). Conclusions: The risk of bacterial and fungal superinfections in COVID-19 is consistent. Patients who need empiric broad-spectrum antibiotics and immunomodulant drugs should be carefully selected. Infection control rules must be reinforced.