Cefiderocol treatment for carbapenem-resistant Acinetobacter baumannii infection in the ICU during the COVID-19 pandemic: a multicentre cohort study

open16noFunding: This study was carried out as part of our routine work and supported by internal funding.Objectives: 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.Methods: 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.Results: 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).Conclusions: Our study confirms the potential role of cefiderocol in the treatment of CR-Ab infection, but larger clinical studies are needed.openPascale, Renato; Pasquini, Zeno; Bartoletti, Michele; Caiazzo, Luca; Fornaro, Giacomo; Bussini, Linda; Volpato, Francesca; Marchionni, Elisa; Rinaldi, Matteo; Trapani, Filippo; Temperoni, Chiara; Gaibani, Paolo; Ambretti, Simone; Barchiesi, Francesco; Viale, Pierluigi; Giannella, MaddalenaPascale, Renato; Pasquini, Zeno; Bartoletti, Michele; Caiazzo, Luca; Fornaro, Giacomo; Bussini, Linda; Volpato, Francesca; Marchionni, Elisa; Rinaldi, Matteo; Trapani, Filippo; Temperoni, Chiara; Gaibani, Paolo; Ambretti, Simone; Barchiesi, Francesco; Viale, Pierluigi; Giannella, Maddalen

Intein-mediated protein trans-splicing expands adeno-associated virus transfer capacity in the retina

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Potential role of T2Candida in the management of empirical antifungal treatment in patients at high risk of candidaemia: a pilot single-centre study

Objectives: We estimated the diagnostic accuracy of T2Candida, with blood culture (BC) as the gold standard, and compared turnaround time between these two techniques in order to investigate the potential role of T2Candida in the management of empirical antifungal treatment (EAT). Methods: We performed a single-centre prospective observational study in patients with severe sepsis or septic shock and multiple risk factors for candidaemia. Results: We analysed 46 out of 50 screened patients. All patients received an echinocandin as EAT; the median EAT duration was 7 days (IQR 4\u201313 days). BCs were negative in 31 (67.4%) patients, positive for bacteria in 14 (30.4%) patients and positive for Candida albicans in 1 (2.2%) patient. T2Candida was negative, invalid and positive in 37, 5 and 4 patients, respectively. T2Candida and BC results were concordant in all but three patients, where T2Candida was positive and BCs were negative. Two of them were on antifungal prophylaxis at the time of enrolment. T2Candida reduced time to a negative result by 5 days. T2Candida performance was: sensitivity "100% (95% CI 2.5%\u2013100%), specificity" 91.8% (95% CI 78%\u201398%), positive predictive value "25% (95% CI 0.63%\u201380.6%) and negative predictive value " 100% (95% CI 89.7%\u2013100%). Conclusions: In patients with multiple risk factors for candidaemia and severe sepsis or septic shock, T2Candida may be helpful to reduce the length of EAT

Native Mitral Valve Endocarditis Caused by Neisseria elongata subsp. nitroreducens in a Patient with Marfan Syndrome: First Case in Italy and Review of the Literature

Neisseria elongata (NE) is an aerobic Gram-negative organism that constitutes part of the commensal human normal oropharyngeal flora. Although previously considered not to be pathogenic, it has been recognized as an occasional cause of significant infections in humans. We report here the first case in Italy of infective endocarditis of a native prolapsing mitral valve in a patient with Marfan syndrome, caused by NE subspecies nitroreducens which has been rarely isolated from clinical specimens. The culprit organism has been confirmed by mass spectrometry directly from the positive blood culture, as previously reported. The amplified gene has been deposited in GenBank under accession number KT591873. In spite of the reported aggressive nature of NE, clinical remission was promptly obtained, there being no requirement for surgery

Epidemiology of invasive pulmonary aspergillosis among COVID-19 intubated patients: a prospective study

BACKGROUND: In this study we evaluated the incidence of invasive pulmonary aspergillosis among intubated patients with critical coronavirus disease 2019 (COVID-19) and evaluated different case definitions of invasive aspergillosis.METHODS: Prospective, multicentre study on adult patients with microbiologically confirmed COVID-19 receiving mechanical ventilation. All included participants underwent 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).RESULTS: A total of 108 patients were enrolled. Probable CAPA was diagnosed in 30 (27.7%) of patients after a median of 4 (2-8) days from intensive care unit (ICU) admission. Kaplan-Meier curves showed a significant higher 30-day mortality rate from ICU admission among patients with either CAPA (44% vs 19%, p= 0.002) or PIPA (74% vs 26%, p<0.001) when compared with patients not fulfilling criteria for aspergillosis. The association between CAPA [OR 3.53 (95%CI 1.29-9.67), P=0.014] or PIPA [OR 11.60 (95%CI 3.24-41.29) p<0.001] 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=0.30) and reduction of galactomannan index in consecutive samples was observed.CONCLUSION: We found a high incidence of CAPA among critically ill COVID-19 patients and that its occurrence seems to change the natural history of disease