Background Few small studies have described hospital-acquired infections (HAIs) during COVID-19. Research Question What patient characteristics in critically ill patients with COVID-19 are associated with HAIs and how do HAIs associate with outcomes in these patients? Study Design and Methods Multicenter retrospective analysis of prospectively collected data including adult patients with severe COVID-19, admitted to 8 Italian hub hospitals from February 20, 2020, to May 20, 2020. Descriptive statistics, univariable and multivariable Weibull regression models were used to assess incidence, microbial etiology, resistance patterns, risk factors (i.e., demographics, comorbidities, exposure to medication), and impact on outcomes (i.e., ICU survival, length of ICU and hospital stay and duration of mechanical ventilation) of microbiologically-confirmed HAIs. Results Of the 774 included patients, 359 (46%) patients developed 759 HAIs (44.7 infections/1000 ICU patient-days, 35% multi-drug resistant (MDR) bacteria). Ventilator-associated pneumonia (VAP) (389, 50%), bloodstream infections (183, 34%), and catheter related blood stream infections (74, 10%) were the most frequent HAIs, with 26.0 (23.6-28.8) VAPs/1000 patient intubation-days, 11.7(10.1-13.5) BSIs/1000 ICU patient-days, and 4.7 (3.8-5.9) CRBSIs/1000 patient-days. Gram-negative bacteria (especially Enterobacterales ) and Staphylococcus aureus caused 64% and 28% of VAPs. Variables independently associated with infection were age, PEEP and treatment with broad-spectrum antibiotic at admission. 234 patients (30%) died in ICU (15.3 deaths/1000 ICU patient-days). Patients with HAIs complicated by septic shock had almost doubled mortality (52% vs. 29%), while non-complicated infections did not affect mortality. HAIs prolonged mechanical ventilation (24(14-39) vs. 9(5-13) days; p<0.001), ICU and hospital stay (24(16-41) vs. 9(6-14) days, p=0.003; and (42(25-59) vs. 23(13-34) days, p<0.001). Interpretation Critically-ill COVID-19 patients are at high risk for HAIs, especially VAPs and BSIs due to MDR organisms. HAIs prolong mechanical ventilation and hospitalization, and HAIs complicated by septic-shock almost doubled mortality.

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Infections (especially ventilator-associated pneumonia) during extracorporeal membrane oxygenation therapy are common and frequently involve multidrug-resistant organisms. In addition, they have a negative impact on patients' outcomes.

Background: Immunomodulants have been proposed to mitigate severe acute respiratory syndrome coronavirus 2-induced cytokine storm, which drives acute respiratory distress syndrome in coronavirus disease 2019 . Objective: We sought to determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation. Methods: A secondary analysis of prospective observational cohort studies was carried out at an Italian tertiary health care facility. COVID-19 patients consecutively hospitalized (February 25, 2020, to March 30, 2020 with hyperinflammation (ferritin > _1000 ng/mL and/or C-reactive protein >10 mg/dL) and respiratory failure (oxygen therapy from 0.4 FiO 2 Venturi mask to invasive mechanical ventilation) were evaluated to investigate the effect of high-dose anakinra plus methylprednisolone on survival. Patients were followed from study inclusion to day 28 or death. Crude and adjusted (sex, age, baseline PaO 2 :FiO 2 ratio, Charlson index, baseline mechanical ventilation, hospitalization to inclusion lapse) risks were calculated (Cox proportional regression model). Results: A total of 120 COVID-19 patients with hyperinflammation (median age, 62 years; 80.0% males; median PaO 2 :FiO 2 ratio, 151; 32.5% on mechanical ventilation) were evaluated. Of these, 65 were treated with anakinra and methylprednisolone and 55 were untreated historical controls. At 28 days, mortality was 13.9% in treated patients and 35.6% in controls (Kaplan-Meier plots, P 5 .005). Unadjusted and adjusted risk of death was significantly lower for treated patients compared with controls (hazard ratio, 0.33, 95% CI, 0.15-0.74, P 5 .007, and HR, 0.18, 95% CI, 0.07-0.50, P 5 .001, respectively). No significant differences in bloodstream infections or laboratory alterations were registered. Conclusions: Treatment with anakinra plus methylprednisolone may be a valid therapeutic option in COVID-19 patients with hyperinflammation and respiratory failure, also on mechanical ventilation. Randomized controlled trials including the use of either agent alone are needed to confirm these results. (J Allergy Clin Immunol 2021;147:561-6.)

Repeat episodes of infective endocarditis (IE) can occur in patients who survive an initial episode. We analysed risk factors and 1-year mortality of patients with repeat IE. We considered 1874 patients enrolled in the International Collaboration on Endocarditis - Prospective Cohort Study between January 2000 and December 2006 (ICE-PCS) who had definite native or prosthetic valve IE and 1-year follow-up. Multivariable analysis was used to determine risk factors for repeat IE and 1-year mortality. Of 1874 patients, 1783 (95.2%) had single-episode IE and 91 (4.8%) had repeat IE: 74/91 (81%) with new infection and 17/91 (19%) with presumed relapse. On bivariate analysis, repeat IE was associated with haemodialysis (p 0.002), HIV (p 0.009), injection drug use (IDU) (p < 0.001), Staphylococcus aureus IE (p 0.003), healthcare acquisition (p 0.006) and previous IE before ICE enrolment (p 0.001). On adjusted analysis, independent risk factors were haemodialysis (OR, 2.5; 95% CI, 1.2-5.3), IDU (OR, 2.9; 95% CI, 1.6-5.4), previous IE (OR, 2.8; 95% CI, 1.5-5.1) and living in the North American region (OR, 1.9; 95% CI, 1.1-3.4). Patients with repeat IE had higher 1-year mortality than those with single-episode IE (p 0.003). Repeat IE is associated with IDU, previous IE and haemodialysis. Clinicians should be aware of these risk factors in order to recognize patients who are at risk of repeat IE.