We evaluated the incidence of invasive pulmonary aspergillosis among intubated patients with critical COVID-19 and evaluated different case definitions of invasive aspergillosis. Prospective, multicenter study in adult patients with microbiologically confirmed COVID-19 receiving mechanical ventilation. All included participants underwent a screening protocol for invasive pulmonary aspergillosis with bronchoalveolar lavage galactomannan and cultures performed on admission at 7 days and in case of clinical deterioration. Cases were classified as coronavirus-associated pulmonary aspergillosis (CAPA) according to previous consensus definitions. The new definition was compared with putative invasive pulmonary aspergillosis (PIPA). 108 patients were enrolled. Probable CAPA was diagnosed in 30 (27.7%) patients after a median of 4 (2–8) days from intensive care unit (ICU) admission. Kaplan-Meier curves showed a significantly higher 30-day mortality rate from ICU admission among patients with either CAPA (44% vs 19%, P = .002) or PIPA (74% vs 26%, P < .001) when compared with patients not fulfilling criteria for aspergillosis. The association between CAPA (OR, 3.53; 95% CI, 1.29–9.67; P = .014) or PIPA (OR, 11.60; 95% CI, 3.24–41.29; P < .001) with 30-day mortality from ICU admission was confirmed, even after adjustment for confounders with a logistic regression model. Among patients with CAPA receiving voriconazole treatment (13 patients; 43%) a trend toward lower mortality (46% vs 59%; P = .30) and reduction in galactomannan index in consecutive samples were observed. We found a high incidence of CAPA among critically ill COVID-19 patients and its occurrence seems to change the natural course of disease.

The primary objective of this multicenter, observational, retrospective study was to assess the incidence rate of ventilator-associated pneumonia (VAP) in coronavirus disease 2019 (COVID-19) patients in intensive care units (ICU). The secondary objective was to assess predictors of 30-day case-fatality of VAP. From 15 February to 15 May 2020, 586 COVID-19 patients were admitted to the participating ICU. Of them, 171 developed VAP (29%) and were included in the study. The incidence rate of VAP was of 18 events per 1000 ventilator days (95% confidence intervals [CI] 16–21). Deep respiratory cultures were available and positive in 77/171 patients (45%). The most frequent organisms were Pseudomonas aeruginosa (27/77, 35%) and Staphylococcus aureus (18/77, 23%). The 30-day case-fatality of VAP was 46% (78/171). In multivariable analysis, septic shock at VAP onset (odds ratio [OR] 3.30, 95% CI 1.43–7.61, p = 0.005) and acute respiratory distress syndrome at VAP onset (OR 13.21, 95% CI 3.05–57.26, p < 0.001) were associated with fatality. In conclusion, VAP is frequent in critically ill COVID-19 patients. The related high fatality is likely the sum of the unfavorable prognostic impacts of the underlying viral and the superimposed bacterial diseases.

To analyse the impact of cefiderocol use on outcome in patients admitted to the ICU for severe COVID-19 and further diagnosed with carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection. Retrospective multicentre observational study was performed at four Italian hospitals, from January 2020 to April 2021. Adult patients admitted to ICU for severe COVID-19 and further diagnosed with CR-Ab infections were enrolled. Patients treated with cefiderocol, as compassionate use, for at least 72 h were compared with those receiving alternative regimens. Primary endpoint was all-cause 28 day mortality. The impact of cefiderocol on mortality was evaluated by multivariable Cox regression model. In total, 107 patients were enrolled (76% male, median age 65 years). The median time from ICU admission to CR-Ab infection diagnosis was 14 (IQR 8–20) days, and the main types of CR-Ab infections were bloodstream infection (58%) and lower respiratory tract infection (41%). Cefiderocol was administered to 42 patients within a median of 2 (IQR 1–4) days after CR-Ab infection diagnosis and as monotherapy in all cases. The remaining patients received colistin, mostly (82%) administered as combination therapy. All-cause 28 day mortality rate was 57%, without differences between groups (cefiderocol 55% versus colistin 58% P = 0.70). In multivariable analysis, the independent risk factor for mortality was SOFA score (HR 1.24, 95% CI 1.15–1.38, P < 0.001). Cefiderocol was associated with a non-significant lower mortality risk (HR 0.64, 95% CI 0.38–1.08, P = 0.10). Our study confirms the potential role of cefiderocol in the treatment of CR-Ab infection, but larger clinical studies are needed.