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

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. A multivariate 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.