Publications by authors named "Matteo Bassetti"

444 Publications

The role of PCSK9 in infectious diseases.

Curr Med Chem 2021 Jul 14. Epub 2021 Jul 14.

Infectious Diseases Unit, San Martino Policlinico Hospital - IRCCS, Genoa, Italy.

Background: In recent years, many aspects of the physiological role of PCSK9 have been elucidated, particularly regarding its role in lipid metabolism, cardiovascular risk, and its role in innate immunity. Increasing evidence is available about the involvement of PCSK9 in the pathogenesis of viral infections, mainly HCV, and the regulation of host response to bacterial infections, primarily sepsis and septic shock. Moreover, the action of PCSK9 has been investigated as a crucial step in the pathogenesis of malaria infection and disease severity.

Objective: This paper aims to review the available published literature on the role of PCSK9 in a wide array of infectious diseases.

Conclusion: Besides the ongoing investigation on PCSK9 inhibition among HIV-infected patients to treat HIV- and ART-related hyperlipidemia, preclinical studies indicate how PCSK9 is involved in reducing the replication of HCV. Interestingly, high plasmatic PCSK9 levels have been described in patients with sepsis. Moreover, a protective role of PCSK9 inhibition has also been proposed against dengue and SARS-CoV-2 viral infections. Finally, a loss of function in the PCSK9-encoding gene has been reported to reduce malaria infection mortality.
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http://dx.doi.org/10.2174/0929867328666210714160343DOI Listing
July 2021

Early Effects of Passive Leg-Raising Test, Fluid Challenge, and Norepinephrine on Cerebral Autoregulation and Oxygenation in COVID-19 Critically Ill Patients.

Front Neurol 2021 16;12:674466. Epub 2021 Jun 16.

Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.

Coronavirus disease 2019 (COVID-19) patients are at high risk of neurological complications consequent to several factors including persistent hypotension. There is a paucity of data on the effects of therapeutic interventions designed to optimize systemic hemodynamics on cerebral autoregulation (CA) in this group of patients. Single-center, observational prospective study conducted at San Martino Policlinico Hospital, Genoa, Italy, from October 1 to December 15, 2020. Mechanically ventilated COVID-19 patients, who had at least one episode of hypotension and received a passive leg raising (PLR) test, were included. They were then treated with fluid challenge (FC) and/or norepinephrine (NE), according to patients' clinical conditions, at different moments. The primary outcome was to assess the early effects of PLR test and of FC and NE [when clinically indicated to maintain adequate mean arterial pressure (MAP)] on CA (CA index) measured by transcranial Doppler (TCD). Secondary outcomes were to evaluate the effects of PLR test, FC, and NE on systemic hemodynamic variables, cerebral oxygenation (rSo), and non-invasive intracranial pressure (nICP). Twenty-three patients were included and underwent PLR test. Of these, 22 patients received FC and 14 were treated with NE. The median age was 62 years (interquartile range = 57-68.5 years), and 78% were male. PLR test led to a low CA index [58% (44-76.3%)]. FC and NE administration resulted in a CA index of 90.8% (74.2-100%) and 100% (100-100%), respectively. After PLR test, nICP based on pulsatility index and nICP based on flow velocity diastolic formula was increased [18.6 (17.7-19.6) vs. 19.3 (18.2-19.8) mm Hg, = 0.009, and 12.9 (8.5-18) vs. 15 (10.5-19.7) mm Hg, = 0.001, respectively]. PLR test, FC, and NE resulted in a significant increase in MAP and rSo. In mechanically ventilated severe COVID-19 patients, PLR test adversely affects CA. An individualized strategy aimed at assessing both the hemodynamic and cerebral needs is warranted in patients at high risk of neurological complications.
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http://dx.doi.org/10.3389/fneur.2021.674466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242251PMC
June 2021

Tracheostomy Timing and Outcome in Severe COVID-19: The WeanTrach Multicenter Study.

J Clin Med 2021 Jun 16;10(12). Epub 2021 Jun 16.

Department of Health Sciences, Section of Biostatistics, University of Genoa, 16132 Genoa, Italy.

Background: Tracheostomy can be performed safely in patients with coronavirus disease 2019 (COVID-19). However, little is known about the optimal timing, effects on outcome, and complications.

Methods: A multicenter, retrospective, observational study. This study included 153 tracheostomized COVID-19 patients from 11 intensive care units (ICUs). The primary endpoint was the median time to tracheostomy in critically ill COVID-19 patients. Secondary endpoints were survival rate, length of ICU stay, and post-tracheostomy complications, stratified by tracheostomy timing (early versus late) and technique (surgical versus percutaneous).

Results: The median time to tracheostomy was 15 (1-64) days. There was no significant difference in survival between critically ill COVID-19 patients who received tracheostomy before versus after day 15, nor between surgical and percutaneous techniques. ICU length of stay was shorter with early compared to late tracheostomy ( < 0.001) and percutaneous compared to surgical tracheostomy ( = 0.050). The rate of lower respiratory tract infections was higher with surgical versus percutaneous technique ( = 0.007).

Conclusions: Among critically ill patients with COVID-19, neither early nor percutaneous tracheostomy improved outcomes, but did shorten ICU stay. Infectious complications were less frequent with percutaneous than surgical tracheostomy.
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http://dx.doi.org/10.3390/jcm10122651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235219PMC
June 2021

Use of Ceftaroline in Hospitalized Patients with and without COVID-19: A Descriptive Cross-Sectional Study.

Antibiotics (Basel) 2021 Jun 23;10(7). Epub 2021 Jun 23.

Department of Health Sciences, University of Genoa, 16132 Genoa, Italy.

A single-center cross-sectional study was conducted to describe the use of ceftaroline in a large teaching hospital in Northern Italy, during a period also including the first months of the coronavirus disease 2019 (COVID-19) pandemic. The primary objective was to describe the use of ceftaroline in terms of indications and characteristics of patients. A secondary objective was to describe the rate of favorable clinical response in patients with bloodstream infections (BSI) due to methicillin-resistant (MRSA-BSI) receiving ceftaroline. Overall, 200 patients were included in the study. Most of them had COVID-19 (83%, 165/200) and were hospitalized in medical wards (78%, 155/200). Included patients with COVID-19 pneumonia were given empirical ceftaroline in the suspicion of bacterial co-infection or superinfection. Among patients with MRSA-BSI, ceftaroline was used as a first-line therapy and salvage therapy in 25% (3/12) and 75% (9/12) of cases, respectively, and as a monotherapy or in combination with daptomycin in 58% (7/12) and 42% (5/12) of patients, respectively. A favorable response was registered in 67% (8/12) of patients. Improving etiological diagnosis of bacterial infections is essential to optimize the use of ceftaroline in COVID-19 patients. The use of ceftaroline for MRSA-BSI, either as a monotherapy or in combination with other anti-MRSA agents, showed promising rates of favorable response.
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http://dx.doi.org/10.3390/antibiotics10070763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300614PMC
June 2021

Recent advances and future perspectives in the pharmacological treatment of infections.

Expert Rev Clin Pharmacol 2021 Jul 15:1-16. Epub 2021 Jul 15.

Department of Health Sciences, University of Genoa, Genoa, Italy.

Introduction: is responsible for hospital outbreaks worldwide. Some isolates may show concomitant resistance to azoles, echinocandins, and polyenes, thereby possibly leaving clinicians with few therapeutic options.

Areas Covered: Antifungal agents both in early and in late phases of clinical development showing anti- activity.

Expert Opinion: The research on antifungal agents active against has made important steps forward in recent years: () the development of drugs with novel mechanisms of action, such as ibrexafungerp and fosmanogepix, could provide a valid option against strains resistant to one or more older antifungals, including pan-resistant strains; () rezafungin could allow once weekly administration of an active drug in the case of echinocandin-susceptible isolates, providing an effective outpatient treatment, while at the same time relieving selective pressure on novel classes; the development of oral formulations could allow step-down therapy and/or early discharge, or even to avoid hospitalization in mild or noninvasive diseases; () according to available data, these novel agents show a good safety profile and a low potential for drug-drug interactions.
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http://dx.doi.org/10.1080/17512433.2021.1949285DOI Listing
July 2021

Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis.

Intensive Care Med 2021 Aug 23;47(8):819-834. Epub 2021 Jun 23.

Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James's Hospital, Dublin, Ireland.

Purpose: Invasive pulmonary aspergillosis (IPA) is increasingly reported in patients with severe coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Diagnosis and management of COVID-19 associated pulmonary aspergillosis (CAPA) are challenging and our aim was to develop practical guidance.

Methods: A group of 28 international experts reviewed current insights in the epidemiology, diagnosis and management of CAPA and developed recommendations using GRADE methodology.

Results: The prevalence of CAPA varied between 0 and 33%, which may be partly due to variable case definitions, but likely represents true variation. Bronchoscopy and bronchoalveolar lavage (BAL) remain the cornerstone of CAPA diagnosis, allowing for diagnosis of invasive Aspergillus tracheobronchitis and collection of the best validated specimen for Aspergillus diagnostics. Most patients diagnosed with CAPA lack traditional host factors, but pre-existing structural lung disease and immunomodulating therapy may predispose to CAPA risk. Computed tomography seems to be of limited value to rule CAPA in or out, and serum biomarkers are negative in 85% of patients. As the mortality of CAPA is around 50%, antifungal therapy is recommended for BAL positive patients, but the decision to treat depends on the patients' clinical condition and the institutional incidence of CAPA. We recommend against routinely stopping concomitant corticosteroid or IL-6 blocking therapy in CAPA patients.

Conclusion: CAPA is a complex disease involving a continuum of respiratory colonization, tissue invasion and angioinvasive disease. Knowledge gaps including true epidemiology, optimal diagnostic work-up, management strategies and role of host-directed therapy require further study.
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http://dx.doi.org/10.1007/s00134-021-06449-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220883PMC
August 2021

Prevalence and prognostic value of cardiac troponin in elderly patients hospitalized for COVID-19.

J Geriatr Cardiol 2021 May;18(5):338-345

Cardiovascular Diseases Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

Background: Increases in cardiac troponin (cTn) in coronavirus disease 2019 (COVID-19) have been associated with worse prognosis. Nonetheless, data about the significance of cTn in elderly subjects with COVID-19 are lacking.

Methods: From a registry of consecutive patients with COVID-19 admitted to a hub hospital in Italy from 25/02/2020 to 03/07/2020, we selected those ≥ 60 year-old and with cTnI measured within three days from the molecular diagnosis of SARS-CoV-2 infection. When available, a second cTnI value within 48 h was also extracted. The relationship between increased cTnI and all-cause in-hospital mortality was evaluated by a Cox regression model and restricted cubic spline functions with three knots.

Results: Of 343 included patients (median age: 75.0 (68.0-83.0) years, 34.7% men), 88 (25.7%) had cTnI above the upper-reference limit (0.046 µg/L). Patients with increased cTnI had more comorbidities, greater impaired respiratory exchange and higher inflammatory markers on admission than those with normal cTnI. Furthermore, they died more (73.9%. 37.3%, < 0.001) over 15 (6-25) days of hospitalization. The association of elevated cTnI with mortality was confirmed by the adjusted Cox regression model (HR = 1.61, 95%CI: 1.06-2.52, = 0.039) and was linear until 0.3 µg/L, with a subsequent plateau. Of 191 (55.7%) patients with a second cTnI measurement, 49 (25.7%) had an increasing trend, which was not associated with mortality (univariate HR = 1.39, 95%CI: 0.87-2.22, = 0.265).

Conclusions: In elderly COVID-19 patients, an initial increase in cTn is common and predicts a higher risk of death. Serial cTn testing may not confer additional prognostic information.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2021.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185447PMC
May 2021

Lung distribution of gas and blood volume in critically ill COVID-19 patients: a quantitative dual-energy computed tomography study.

Crit Care 2021 06 21;25(1):214. Epub 2021 Jun 21.

Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV 16, Genoa, Italy.

Background: Critically ill COVID-19 patients have pathophysiological lung features characterized by perfusion abnormalities. However, to date no study has evaluated whether the changes in the distribution of pulmonary gas and blood volume are associated with the severity of gas-exchange impairment and the type of respiratory support (non-invasive versus invasive) in patients with severe COVID-19 pneumonia.

Methods: This was a single-center, retrospective cohort study conducted in a tertiary care hospital in Northern Italy during the first pandemic wave. Pulmonary gas and blood distribution was assessed using a technique for quantitative analysis of dual-energy computed tomography. Lung aeration loss (reflected by percentage of normally aerated lung tissue) and the extent of gas:blood volume mismatch (percentage of non-aerated, perfused lung tissue-shunt; aerated, non-perfused dead space; and non-aerated/non-perfused regions) were evaluated in critically ill COVID-19 patients with different clinical severity as reflected by the need for non-invasive or invasive respiratory support.

Results: Thirty-five patients admitted to the intensive care unit between February 29th and May 30th, 2020 were included. Patients requiring invasive versus non-invasive mechanical ventilation had both a lower percentage of normally aerated lung tissue (median [interquartile range] 33% [24-49%] vs. 63% [44-68%], p < 0.001); and a larger extent of gas:blood volume mismatch (43% [30-49%] vs. 25% [14-28%], p = 0.001), due to higher shunt (23% [15-32%] vs. 5% [2-16%], p = 0.001) and non-aerated/non perfused regions (5% [3-10%] vs. 1% [0-2%], p = 0.001). The PaO/FiO ratio correlated positively with normally aerated tissue (ρ = 0.730, p < 0.001) and negatively with the extent of gas-blood volume mismatch (ρ = - 0.633, p < 0.001).

Conclusions: In critically ill patients with severe COVID-19 pneumonia, the need for invasive mechanical ventilation and oxygenation impairment were associated with loss of aeration and the extent of gas:blood volume mismatch.
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http://dx.doi.org/10.1186/s13054-021-03610-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215486PMC
June 2021

The Role of Dysbiosis in Critically Ill Patients With COVID-19 and Acute Respiratory Distress Syndrome.

Front Med (Lausanne) 2021 4;8:671714. Epub 2021 Jun 4.

Anesthesia and Intensive Care, Ospedale Policlinico San Martino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) per l'Oncologia e le Neuroscienze, Genova, Italy.

In late December 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) quickly spread worldwide, and the syndrome it causes, coronavirus disease 2019 (COVID-19), has reached pandemic proportions. Around 30% of patients with COVID-19 experience severe respiratory distress and are admitted to the intensive care unit for comprehensive critical care. Patients with COVID-19 often present an enhanced immune response with a hyperinflammatory state characterized by a "cytokine storm," which may reflect changes in the microbiota composition. Moreover, the evolution to acute respiratory distress syndrome (ARDS) may increase the severity of COVID-19 and related dysbiosis. During critical illness, the multitude of therapies administered, including antibiotics, sedatives, analgesics, body position, invasive mechanical ventilation, and nutritional support, may enhance the inflammatory response and alter the balance of patients' microbiota. This status of dysbiosis may lead to hyper vulnerability in patients and an inappropriate response to critical circumstances. In this context, the aim of our narrative review is to provide an overview of possible interaction between patients' microbiota dysbiosis and clinical status of severe COVID-19 with ARDS, taking into consideration the characteristic hyperinflammatory state of this condition, respiratory distress, and provide an overview on possible nutritional strategies for critically ill patients with COVID-19-ARDS.
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http://dx.doi.org/10.3389/fmed.2021.671714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211890PMC
June 2021

Does syphilis increase the risk of HIV-RNA elevation >200 copies/mL in HIV positive patients under effective antiretroviral treatment? Data from the ICONA cohort.

J Acquir Immune Defic Syndr 2021 Jun 15. Epub 2021 Jun 15.

III Infectious Diseases Unit, ASST-FBF-Sacco, Department of Biomedical and Clinical Sciences DIBIC Luigi Sacco, Università di Milano, Milan, Italy. Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London, UK. Infectious Diseases Unit, Fondazione Policlinico Universitario A. Gemelli - Università Cattolica Del Sacro Cuore, Rome, Italy. ICONA Foundation, Milan, Italy. HIV/AIDS Unit, INMI "Lazzaro Spallanzani" IRCCS, Rome, Italy. Clinic of Infectious and Tropical Diseases, ASST Santi Paolo e Carlo, University of Milan Department of Health Sciences, Milan, Italy. Infectious Diseases Clinic, Policlinico San Martino Hospital, Department of Health Sciences, University of Genoa, Genova, Italy. Infectious Diseases, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy. Infectious Diseases Unit, Sapienza University of Rome, Santa Maria Goretti Hospital, Latina, Italy.

Background: To assess the impact of syphilis infection on the risk of HIV-RNA elevation in people living with HIV (PLWH) with current HIV-RNA ≤50 copies/mL.

Setting: The Italian Cohort Naïve Antiretrovirals (ICONA).

Methods: All PLWH (2009-2020) under antiretroviral treatment with at least 2 consecutive HIV-RNA values ≤50 copies/mL before the date of syphilis diagnosis and at least one HIV-RNA determination after the syphilis event were enrolled. A control group of PLWH without syphilis was matched for mode of HIV transmission. Outcomes were defined using the first HIV-RNA measure in the time window ranging between -2 and +6 months of the diagnosis/index date. The primary outcome used a single value>200 copies/mL to define HIV-RNA elevation associated with risk of transmission. The association between syphilis infection and the protocol defined outcome was evaluated using logistic regression analysis.

Results: Nine hundred and twenty-six PLWH with a syphilis event were enrolled and matched with a random sample of 1370 PLWH without syphilis. Eighteen of the 926 (1.9%) with syphilis had ≥1 HIV-RNA>200 copies/mL in the window vs. 29/1370 (2.1%) of the not exposed (p=0.77). In the multivariable analysis adjusted for age, year of diagnosis/index date and clinical site, syphilis infection was not associated with the risk of HIV-RNA >200 copies/mL [adjusted Odds Ratio 0.81; 95% confidence interval 0.43-1.52, p=0.508].

Conclusions: We did not find any evidence for an association between syphilis infection and viral elevation >200 copies/mL.
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http://dx.doi.org/10.1097/QAI.0000000000002749DOI Listing
June 2021

Promoting cross-regional collaboration in antimicrobial stewardship: Findings of an infectious diseases working group survey in Arab countries of the Middle East.

J Infect Public Health 2021 Jul 24;14(7):978-984. Epub 2021 Apr 24.

American University of Beirut Medical Center, Beirut, Lebanon. Electronic address:

Background: Antimicrobial resistance is a significant global issue that presents an increasing threat to patients' wellbeing. Although a global concern, the emergence of multi-drug resistant organisms is of particular significance in the Middle East. In recent years, this region has seen an alarming increase in antimicrobial resistance presenting a major challenge to physicians managing various infectious diseases.

Methods: A Working Group comprising experts in infectious diseases from Arab countries of Middle East assembled to review similarities and differences in antimicrobial practices and management of multi-drug resistant organisms across the region and assess the barriers to achieving cross-regional collaboration. The Working Group conducted an anonymous online survey to evaluate current practice and understanding of management of multi-drug resistant organisms across the region.

Results: A total of 122 physicians from Arab countries of the Middle East responded to the survey. Their responses demonstrated heterogeneity between countries in awareness of local epidemiology, management of multi-drug resistant organisms and antimicrobial stewardship practices. The Working Group recognized similarities and differences in the management of multi-drug resistant organisms across the region, and these were validated by the data collected in the survey. Overall, the similarities across the region reflect several key issues that can have an impact on the management of multi-drug resistant organisms and the prevention of antimicrobial resistance.

Conclusions: This paper highlights the urgency of addressing antimicrobial resistance in Arab countries of the Middle East. The Working Group identified key barriers to effective management which may guide the development of future coherent strategies to promote effective antimicrobial stewardship in the region. Here, we outline a call to action for the region, with a need to focus on training and education, capacity building, infrastructure, regional research, and regional surveillance.
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http://dx.doi.org/10.1016/j.jiph.2021.04.009DOI Listing
July 2021

An Experimental Pre-Post Study on the Efficacy of Respiratory Physiotherapy in Severe Critically III COVID-19 Patients.

J Clin Med 2021 May 15;10(10). Epub 2021 May 15.

Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neuroscience, 16132 Genoa, Italy.

: Respiratory physiotherapy (RPT) is considered essential in patients' management during intensive care unit (ICU) stay. The role of RPT in critically ill COVID-19 patients is poorly described. We aimed to investigate the effects of RPT on oxygenation and lung aeration in critically ill COVID-19 patients admitted to the ICU. : Observational pre-post study. Patients with severe COVID-19 admitted to the ICU, who received a protocolized CPT session and for which a pre-and post-RPT lung ultrasound (LUS) was performed, were included. A subgroup of patients had an available quantitative computed tomography (CT) scan performed within 4 days from RPT. The primary aim was to evaluate whether RPT improved oxygenation; secondary aims included correlations between LUS, CT and response to RPT. : Twenty patients were included. The median (1st-3rd quartile) PaO/FiO was 181 (105-456), 244 (137-497) and 246 (137-482) at baseline (T0), after RPT (T1), and after 6 h (T2), respectively. PaO/FiO improved throughout the study ( = 0.042); particularly, PaO/FiO improved at T1 in respect to T0 ( = 0.011), remaining higher at T2 ( = 0.007) compared to T0. Correlations between LUS, volume of gas (rho = 0.58, 95%CI 0.05-0.85, = 0.033) and hyper-aerated mass at CT scan (rho = 0.54, 95% CI 0.00-0.84, = 0.045) were detected. No significant changes in LUS score were observed before and after RPT. : RPT improved oxygenation and the improvement persisted after 6 h. Oxygenation improvement was not reflected by aeration changes assessed with LUS. Further studies are warranted to assess the efficacy of RPT in COVID-19 ICU patients.
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http://dx.doi.org/10.3390/jcm10102139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156952PMC
May 2021

A Wide Database for Future Studies Aimed at Improving Early Recognition of Candidemia.

Stud Health Technol Inform 2021 May;281:1081-1082

Department of Informatics, Bioengineering, Robotics and System Engineering.

Invasive candidiasis is associated with high morbidity and mortality in critically ill patients, i.e. patients admitted to Intensive Care Units (ICUs) or in surgical wards. There are no clinical signs or specific symptoms and even though early diagnosis risk scores and rapid tests are available, none of such strategies has an equally-optimal level of sensitivity and specificity. In the era of Electronic Health Records (EHRs), several clinical studies exploited Machine Learning (ML) models and large database of features to improve the diagnosis accuracy. The main aim of this work is to build a wide dataset which can be exploited to apply ML models to further improve the early recognition of candidemia at the bedside of patients with compatible signs and symptoms.
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http://dx.doi.org/10.3233/SHTI210354DOI Listing
May 2021

Response.

Chest 2021 Apr 6;159(4):1677-1678. Epub 2021 Apr 6.

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.chest.2020.11.029DOI Listing
April 2021

Real-life experience with ceftolozane/tazobactam in Canada: results from the CLEAR (Canadian LEadership on Antimicrobial Real-life usage) registry.

J Glob Antimicrob Resist 2021 06 11;25:346-350. Epub 2021 May 11.

Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.

Objectives: Ceftolozane/tazobactam is a cephalosporin/β-lactamase inhibitor combination with activity against Gram-negative bacilli. Here we report the use of ceftolozane/tazobactam in Canada using a national registry.

Methods: The CLEAR registry uses a REDCap online survey to capture details associated with clinical use of ceftolozane/tazobactam.

Results: Data from 51 patients treated in 2020 with ceftolozane/tazobactam are available. Infections treated included hospital-acquired bacterial pneumonia (37.3% of patients), ventilator-associated bacterial pneumonia (15.7%), bone and joint infection (11.8%), complicated intra-abdominal infection (7.8%) and complicated skin and skin-structure infection (7.8%). Moreover, 17.6% of patients had bacteraemia and 47.1% were in intensive care. Ceftolozane/tazobactam was primarily used as directed therapy for Pseudomonas aeruginosa infections (92.2% of patients). Ceftolozane/tazobactam was used because of resistance to (86.3%), failure of (11.8%) or adverse effects from (2.0%) previously prescribed antimicrobials. Ceftolozane/tazobactam susceptibility testing was performed on isolates from 88.2% of patients. Ceftolozane/tazobactam was used in combination with another antimicrobial active against Gram-negative bacilli in 39.2% of patients [aminoglycosides (15.7%), fluoroquinolones (9.8%) and colistin/polymyxin B (7.8%)]. The dosage regimen was customised in all patients based on creatinine clearance. The treatment duration was primarily >10 days (60.8% of patients), with microbiological success in 60.5% and clinical success in 64.4% of patients. Moreover, 7.8% of patients had adverse effects not requiring drug discontinuation.

Conclusion: In Canada, ceftolozane/tazobactam is used as directed therapy to treat a variety of severe infections caused by multidrug-resistant P. aeruginosa. It is commonly used in combination with other antimicrobials with relatively high microbiological/clinical cure rates and an excellent safety profile.
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http://dx.doi.org/10.1016/j.jgar.2021.03.025DOI Listing
June 2021

Antiviral treatment selection for SARS-CoV-2 pneumonia.

Expert Rev Respir Med 2021 May 21:1-8. Epub 2021 May 21.

Department of Health Sciences, University of Genoa, Genoa, Italy.

Introduction: Therapy of coronavirus disease 2019 (COVID-19) involves evolving algorithms that include drugs aimed at reducing disease progression by counteracting two different, but intertwined processes: () the damage caused by the virus (with antivirals); () the damage caused by a dysregulated host response (with immunomodulatory agents).

Areas Covered: Herein, we discuss the available evidence on the efficacy and safety of antiviral agents employed over the past months for the treatment of COVID-19, and the reasons to be considered for antiviral selection.

Expert Opinion: The available evidence from randomized controlled trials (RCT) currently discourages the use of lopinavir/ritonavir, hydroxychloroquine, and interferons, which did not show improved efficacy compared to standard care or placebo. Regarding remdesivir, the current body of evidence may conditionally support its use in COVID-19 patients requiring oxygen supplementation but still not requiring invasive mechanical ventilation. Finally, neutralizing monoclonal antibodies have been proven efficacious in reducing the risk of severe disease development if administered early in the course of the disease to patients at risk of progression. The results of the ongoing RCT will certainly be crucial to further improve our understanding of the optimal place in therapy of antiviral agents for COVID-19.
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http://dx.doi.org/10.1080/17476348.2021.1927719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146295PMC
May 2021

Characterization of T lymphocytes in severe COVID-19 patients.

J Med Virol 2021 09 3;93(9):5608-5613. Epub 2021 May 3.

Department of Internal Medicine, Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.

In this observational study, 13 patients with severe COVID-19 and 10 healthy controls were enrolled. The data concerning the analysis of circulating T cells show that, in severe COVID-19 patients, the expansion of these cell compartments is prone to induce antibody response, inflammation (CCR4+ and CCR6+ TFH) and regulation (CD8+ Treg). This pathogenic mechanism could lead us to envision a possible new form of biological target therapy.
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http://dx.doi.org/10.1002/jmv.27037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242373PMC
September 2021

Clinical efficacy of eucaloric ketogenic nutrition in the COVID-19 cytokine storm: A retrospective analysis of mortality and intensive care unit admission.

Nutrition 2021 Mar 7;89:111236. Epub 2021 Mar 7.

Infectious Disease Clinic Genoa University, IRCCS-Policlinic Hospital San Martino, Genoa, Italy.

Objectives: Our primary objective was to explore the effect of a eucaloric ketogenic diet (EKD) on mortality, admission to the intensive care unit, and need for non-invasive ventilation in hospitalized patients with COronaVIrus Disease 19 (COVID-19), in comparison to a eucaloric standard diet. Secondary objectives were verification of the safety and feasibility of the diet and its effects on inflammatory parameters, particularly interleukin-6.

Methods: The study is a retrospective analysis of 34 patients fed with an EKD in comparison to 68 patients fed with a eucaloric standard diet, selected and matched using propensity scores 1:2 to avoid the confounding effect of interfering variables. Our hypothesis was that an EKD would reduce mortality, admission to the intensive care unit, and need for non-invasive ventilation in patients with COVID-19.

Results: The preliminary multivariate analysis showed a statistically significant difference in survival (P = 0.046) and need for the intensive care unit (P = 0.049) for the EKD compared with a eucaloric standard diet. Even considering the EKD start day as a time-dependent variable, the results maintain a positive trend for application of the diet, and it is not possible to reject the null hypothesis (P < 0.05). Interleukin-6 concentrations between t0 and t7 (7 d after the beginning of the diet) in the ketogenic nutrition group show a trend that is almost significant (P = 0.062). The EKD was safe and no adverse events were observed.

Conclusions: These results show a possible therapeutic role of an EKD in the clinical management of COVID-19. Currently, a prospective controlled randomized trial is running to confirm these preliminary data.
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http://dx.doi.org/10.1016/j.nut.2021.111236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937042PMC
March 2021

Resistance to ceftazidime/avibactam in infections and colonisations by KPC-producing Enterobacterales: a systematic review of observational clinical studies.

J Glob Antimicrob Resist 2021 06 23;25:268-281. Epub 2021 Apr 23.

Clinical Microbiology and Virology Unit, 'A. Manzoni' Hospital, Lecco, Italy.

Objectives: Ceftazidime/avibactam (CAZ-AVI), approved in 2015, is an important first-line option for Klebsiella pneumoniae carbapenemase-producing Enterobacterales (KPC-E). Although still uncommon, resistance to CAZ-AVI has emerged and may represent a serious cause of concern.

Methods: We performed a systematic literature review of clinical and microbiological features of infections and colonisations by CAZ-AVI-resistant KPC-E, focused on the in vivo emergence of CAZ-AVI resistance in different clinical scenarios.

Results: Twenty-three papers were retrieved accounting for 42 patients and 57 isolates, mostly belonging to K. pneumoniae ST258 harbouring D179Y substitution in the KPC enzyme. The USA, Greece and Italy accounted for 80% of cases. In one-third of isolates resistance was not associated with previous CAZ-AVI exposure. Moreover, 20% of the strains were colistin-resistant and 80% were extended-spectrum β-lactamase (ESBL)-producers. The majority of infected patients had severe underlying diseases (39% cancer, 22% solid-organ transplantation) and 37% died. The abdomen, lung and blood were the most involved infection sites. Infections by CAZ-AVI-resistant strains were mainly treated with combination therapy (85% of cases), with meropenem being the most common (65%) followed by tigecycline (30%), gentamicin (25%), colistin (25%) and fosfomycin (10%). Despite the emergence of resistance, 35% of patients received CAZ-AVI.

Conclusion: Taken together, these data highlight the need for prompt susceptibility testing including CAZ-AVI for Enterobacterales, at least in critical areas. Resistance to CAZ-AVI is an urgent issue to monitor in order to improve both empirical and targeted CAZ-AVI use as well as the management of patients with infections caused by CAZ-AVI-resistant strains.
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http://dx.doi.org/10.1016/j.jgar.2021.04.001DOI Listing
June 2021

Extensive activation, tissue trafficking, turnover and functional impairment of NK cells in COVID-19 patients at disease onset associates with subsequent disease severity.

PLoS Pathog 2021 04 16;17(4):e1009448. Epub 2021 Apr 16.

Division of Infectious Diseases, Policlinico San Martino Hospital, Genoa, Italy.

The SARS-CoV-2 infection causes severe respiratory involvement (COVID-19) in 5-20% of patients through initial immune derangement, followed by intense cytokine production and vascular leakage. Evidence of immune involvement point to the participation of T, B, and NK cells in the lack of control of virus replication leading to COVID-19. NK cells contribute to early phases of virus control and to the regulation of adaptive responses. The precise mechanism of NK cell dysregulation is poorly understood, with little information on tissue margination or turnover. We investigated these aspects by multiparameter flow cytometry in a cohort of 28 patients hospitalized with early COVID-19. Relevant decreases in CD56brightCD16+/- NK subsets were detected, with a shift of circulating NK cells toward more mature CD56dimCD16+KIR+NKG2A+ and "memory" KIR+CD57+CD85j+ cells with increased inhibitory NKG2A and KIR molecules. Impaired cytotoxicity and IFN-γ production were associated with conserved expression of natural cytotoxicity receptors and perforin. Moreover, intense NK cell activation with increased HLA-DR and CD69 expression was associated with the circulation of CD69+CD103+ CXCR6+ tissue-resident NK cells and of CD34+DNAM-1brightCXCR4+ inflammatory precursors to mature functional NK cells. Severe disease trajectories were directly associated with the proportion of CD34+DNAM-1brightCXCR4+ precursors and inversely associated with the proportion of NKG2D+ and of CD103+ NK cells. Intense NK cell activation and trafficking to and from tissues occurs early in COVID-19, and is associated with subsequent disease progression, providing an insight into the mechanism of clinical deterioration. Strategies to positively manipulate tissue-resident NK cell responses may provide advantages to future therapeutic and vaccine approaches.
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http://dx.doi.org/10.1371/journal.ppat.1009448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081333PMC
April 2021

Bronchoalveolar lavage fluid characteristics and outcomes of invasively mechanically ventilated patients with COVID-19 pneumonia in Genoa, Italy.

BMC Infect Dis 2021 Apr 15;21(1):353. Epub 2021 Apr 15.

Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy.

Background: The primary objective of the study is to describe the cellular characteristics of bronchoalveolar lavage fluid (BALF) of COVID-19 patients requiring invasive mechanical ventilation; the secondary outcome is to describe BALF findings between survivors vs non-survivors.

Materials And Methods: Patients positive for SARS-CoV-2 RT PCR, admitted to ICU between March and April 2020 were enrolled. At ICU admission, BALF were analyzed by flow cytometry. Univariate, multivariate and Spearman correlation analyses were performed.

Results: Sixty-four patients were enrolled, median age of 64 years (IQR 58-69). The majority cells in the BALF were neutrophils (70%, IQR 37.5-90.5) and macrophages (27%, IQR 7-49) while a minority were lymphocytes, 1%, TCD3+ 92% (IQR 82-95). The ICU mortality was 32.8%. Non-survivors had a significantly older age (p = 0.033) and peripheral lymphocytes (p = 0.012) were lower compared to the survivors. At multivariate analysis the percentage of macrophages in the BALF correlated with poor outcome (OR 1.336, CI95% 1.014-1.759, p = 0.039).

Conclusions: In critically ill patients, BALF cellularity is mainly composed of neutrophils and macrophages. The macrophages percentage in the BALF at ICU admittance correlated with higher ICU mortality. The lack of lymphocytes in BALF could partly explain a reduced anti-viral response.
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http://dx.doi.org/10.1186/s12879-021-06015-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049078PMC
April 2021

Tuberculosis treatment outcomes in a rural area of Senegal: a decade of experience from 2010 to 2019 by StopTB Italia.

Future Microbiol 2021 Apr 13;16:399-407. Epub 2021 Apr 13.

Stop TB Italia, Milan, 20159, Italy.

Tuberculosis (TB) unevenly affects individuals across the globe, especially in rural areas of low-income countries. Aim of the study was to assess the impact of social protection to increase TB awareness on treatment outcomes among TB patients in a rural area of Senegal. The study, conducted in Fimela district (Senegal) from 1 January 2010 to 31 December 2019 and the intervention started from 31 January 2013, includes activities to increase awareness, active case finding, active follow-up and social protection. Overall, 435 subjects - mainly male and young - were included in the analysis. Among TB cases, 94% had pulmonary involvement, 87% had no previous TB history, and 6% resulted positive HIV. Improved outcome was observed once intervention began (from 71 to 91%, p < 0.001); whereas mortality decreased (from 15 to 5%; p < 0.001), especially for those HIV co-infected for whom TB mortality rate dropped from 70 to 29%. After beginning the cooperation program, TB treatment success increased as a result of the decline of mortality, especially in people living with HIV.
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http://dx.doi.org/10.2217/fmb-2020-0238DOI Listing
April 2021

Prospective Study on Incidence, Risk Factors and Outcome of Recurrent Infections.

J Clin Med 2021 Mar 8;10(5). Epub 2021 Mar 8.

Infectious Diseases, ASST Lecco Hospital, 23900 Lecco, Italy.

Background: Limited and wide-ranging data are available on the recurrent infection (rCDI) incidence rate.

Methods: We performed a cohort study with the aim to assess the incidence of and risk factors for rCDI. Adult patients with a first CDI, hospitalized in 15 Italian hospitals, were prospectively included and followed-up for 30 d after the end of antimicrobial treatment for their first CDI. A case-control study was performed to identify risk factors associated with 30-day onset rCDI.

Results: Three hundred nine patients with a first CDI were included in the study; 32% of the CDI episodes (99/309) were severe/complicated; complete follow-up was available for 288 patients (19 died during the first CDI episode, and 2 were lost during follow-up). At the end of the study, the crude all-cause mortality rate was 10.7% (33 deaths/309 patients). Two hundred seventy-one patients completed the follow-up; rCDI occurred in 21% of patients (56/271) with an incidence rate of 72/10,000 patient-days. Logistic regression analysis identified exposure to cephalosporin as an independent risk factor associated with rCDI (RR: 1.7; 95% CI: 1.1-2.7, = 0.03).

Conclusion: Our study confirms the relevance of rCDI in terms of morbidity and mortality and provides a reliable estimation of its incidence.
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http://dx.doi.org/10.3390/jcm10051127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962640PMC
March 2021

Early infections after successful transcatheter aortic valve replacement are associated with increased short- and long-term mortality: A single-center study.

Int J Cardiol 2021 06 27;332:48-53. Epub 2021 Mar 27.

DICATOV - Cardiothoracic and Vascular Department, San Martino Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy; Department of Internal Medicine and Medical Specialties (Di.M.I.), Chair of Cardiovascular Diseases, University of Genoa, Genoa, Italy. Electronic address:

Background: We reviewed frequency, microbiological pattern, predictors, and outcomes of early infections following transcatheter aortic valve replacement (TAVR).

Methods: Five hundred thirty-nine patients who underwent successful TAVR at a single, high-volume center between January 2014 and December 2019 were enrolled. We defined early infections as occurring within 30-day from TAVR.

Results: Mean age was 83.5 ± 5.4 years; 230 (42.7%) patients were men. Median follow-up was 12.0 (5.7-18.3) months; 30-day and 1-year death rates were 8/539 (1.5%) and 30/539 (5.6%), respectively. Early infections occurred in 61/539 (11.3%) patients, of whom 2 had infections in two sites. Of the 63 infections, 10 were bloodstream infections (BSI), 5 urinary tract, 27 pulmonary (2 with sepsis), 6 access site infections, 1 enterocolitis, and 14 were clinically diagnosed (no specific site). We observed 31/63 (49.2%) microbiologically-documented infections: Gram+ bacteria were isolated in 12/31 (38.7%), Gram- in 17/31 (54.3%), both Gram+ and Gram- in 2/31 (6.5%); in thirty-two infections no specific pathogen could be isolated (clinically-documented infections). Early infections were more prevalent in patients who died within 30-day (8.2% vs. 0.6%, p < 0.001) or 1-year (14.8% vs. 4.4%, p < 0.001) from TAVR. At multivariable analysis, early infections were independently associated with 30-day (HR: 8.82, 95% CI: 1.11-19.83, p = 0.035) and 1-year mortality (HR: 2.10, 95%CI: 1.28-6.21, p = 0.041). The predictive value for 1-year mortality was maintained even restricting the analysis to documented infections only, or to more severe infections (BSI and pneumonia only) (all p < 0.05).

Conclusions: Early infections occur in 1/10th of TAVR and are associated with increased short- and long-term mortality. Whereas a causal relationship between early infections and the risk of death cannot be unequivocally proven, careful surveillance of infected patients may improve TAVR results.
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http://dx.doi.org/10.1016/j.ijcard.2021.03.065DOI Listing
June 2021

Early effects of ventilatory rescue therapies on systemic and cerebral oxygenation in mechanically ventilated COVID-19 patients with acute respiratory distress syndrome: a prospective observational study.

Crit Care 2021 03 19;25(1):111. Epub 2021 Mar 19.

Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.

Background: In COVID-19 patients with acute respiratory distress syndrome (ARDS), the effectiveness of ventilatory rescue strategies remains uncertain, with controversial efficacy on systemic oxygenation and no data available regarding cerebral oxygenation and hemodynamics.

Methods: This is a prospective observational study conducted at San Martino Policlinico Hospital, Genoa, Italy. We included adult COVID-19 patients who underwent at least one of the following rescue therapies: recruitment maneuvers (RMs), prone positioning (PP), inhaled nitric oxide (iNO), and extracorporeal carbon dioxide (CO) removal (ECCOR). Arterial blood gas values (oxygen saturation [SpO], partial pressure of oxygen [PaO] and of carbon dioxide [PaCO]) and cerebral oxygenation (rSO) were analyzed before (T0) and after (T1) the use of any of the aforementioned rescue therapies. The primary aim was to assess the early effects of different ventilatory rescue therapies on systemic and cerebral oxygenation. The secondary aim was to evaluate the correlation between systemic and cerebral oxygenation in COVID-19 patients.

Results: Forty-five rescue therapies were performed in 22 patients. The median [interquartile range] age of the population was 62 [57-69] years, and 18/22 [82%] were male. After RMs, no significant changes were observed in systemic PaO and PaCO values, but cerebral oxygenation decreased significantly (52 [51-54]% vs. 49 [47-50]%, p < 0.001). After PP, a significant increase was observed in PaO (from 62 [56-71] to 82 [76-87] mmHg, p = 0.005) and rSO (from 53 [52-54]% to 60 [59-64]%, p = 0.005). The use of iNO increased PaO (from 65 [67-73] to 72 [67-73] mmHg, p = 0.015) and rSO (from 53 [51-56]% to 57 [55-59]%, p = 0.007). The use of ECCOR decreased PaO (from 75 [75-79] to 64 [60-70] mmHg, p = 0.009), with reduction of rSO values (59 [56-65]% vs. 56 [53-62]%, p = 0.002). In the whole population, a significant relationship was found between SpO and rSO (R = 0.62, p < 0.001) and between PaO and rSO (R0 0.54, p < 0.001).

Conclusions: Rescue therapies exert specific pathophysiological mechanisms, resulting in different effects on systemic and cerebral oxygenation in critically ill COVID-19 patients with ARDS. Cerebral and systemic oxygenation are correlated. The choice of rescue strategy to be adopted should take into account both lung and brain needs. Registration The study protocol was approved by the ethics review board (Comitato Etico Regione Liguria, protocol n. CER Liguria: 23/2020).
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http://dx.doi.org/10.1186/s13054-021-03537-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978164PMC
March 2021

Personal protective equipment use by healthcare workers in intensive care unit during the early phase of COVID-19 pandemic in Italy: a secondary analysis of the PPE-SAFE survey.

Ther Adv Infect Dis 2021 Jan-Dec;8:2049936121998562. Epub 2021 Feb 25.

Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, Italy. Departement of Anaesthesia, Intensive Care and Emergency, Policlinico Paolo Giaccone, Via del Vespro 129, 90127, Palermo, Italy.

Background: Italy was the first Western country to be heavily affected by COVID-19. Healthcare workers (HCWs) were exposed to a high risk of occupational infection, partially due to insufficient personal protective equipment (PPE) supplies. This study aimed to describe the practices, availability, training, confidence in PPE use and the adverse effects due to extended PPE use, as reported by HCWs in Italy. We also aimed to provide a comparison between Italian data and those from other countries.

Methods: This study was a secondary analysis of a previously published international study, the PPE-SAFE Survey, conducted in April 2020. Data were analysed from the original study database.

Results: We analysed the responses from 380 healthcare workers based in Italy, out of the 2711 respondents to the international survey. Among the Italian respondents, FFP2 and FFP3 respirators or equivalent were the most used masks for routine tasks (respectively 188/380, 50%; and 163/380, 43%). The median time of wearing PPE without taking a break was 5 h [interquartile range (IQR) 4-6], with statistically significant difference from other countries [median 4 h (IQR 2-5)  < 0.0001]. In Italy, 249 out of 380 (65%) HCWs had never performed a formal fit test for a N95 mask or equivalent and 91/380 (24%) never had a partner for donning and doffing procedures. Most of the respondents (299/380, 79%) had received formal training in PPE use at any time.

Conclusion: Most of the surveyed Italian HCWs reported working at above usual capacity, long shifts with PPE without breaks and routine use in intensive care unit of aerosol protection (e.g. FFP2/FFP3), hazmat suits and face shields/visors. The correct adherence to safety procedures (e.g. donning/doffing in pairs, performing fit test) has substantial scope for improvement in the future.
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http://dx.doi.org/10.1177/2049936121998562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922607PMC
February 2021

EORTC/MSGERC Definitions of Invasive Fungal Diseases: Summary of Activities of the Intensive Care Unit Working Group.

Clin Infect Dis 2021 03;72(Suppl 2):S121-S127

Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

The EORTC/MSGERC recently revised and updated the consensus definitions of invasive fungal disease (IFD). These definitions primarily focus on patients with cancer and stem cell or solid-organ transplant patients. They may therefore not be suitable for intensive care unit (ICU) patients. More in detail, while the definition of proven IFD applies to a broad range of hosts, the categories of probable and possible IFD were primarily designed for classical immunocompromised hosts and may therefore not be ideal for other populations. Moreover, the scope of the possible category of IFD has been diminished in the recently revised definitions for classically immunocompromised hosts. Diagnosis of IFD in the ICU presents many challenges, which are different for invasive candidiasis and for invasive aspergillosis. The aim of this article is to review progresses made in recent years and difficulties remaining in the development of definitions applicable in the ICU setting.
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http://dx.doi.org/10.1093/cid/ciaa1751DOI Listing
March 2021

The role of dalbavancin for Gram positive infections in the COVID-19 era: state of the art and future perspectives.

Expert Rev Anti Infect Ther 2021 Mar 16:1-10. Epub 2021 Mar 16.

Department of Medical and Surgical Sciences, University of Bologna - IRRCS Policlinico St Orsola, Bologna, Italy.

Introduction: The COVID-19 pandemic has dramatically challenged the national health systems worldwide in the last months. Dalbavancin is a novel antibiotic with a long plasmatic half-life and simplified weekly administration regimens, thus representing a promising option for the outpatient treatment of Gram-positive infections and the early discharge of hospitalized patients. Dalbavancin is approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Many preliminary data seem to support its use in other indications, such as osteomyelitis, prosthetic joint infections, and infective endocarditis.

Areas Covered: A search in the literature using validated keywords (dalbavancin, Gram-positive infections, Gram-positive cocci, ABSSSI, intravenous treatment, and long-acting antibiotics) was conducted on biomedical bibliographic databases (PubMed and Embase) from 2004 to 30 September 2020. Results were analyzed during two consensus conferences with the aim to review the current evidence on dalbavancin in Gram-positive infections, mainly ABSSSI, osteomyelitis, and infective endocarditis, highlight the main limitations of available studies and suggest possible advantages of the molecule.

Expert Opinion: The board identifies some specific subgroups of patients with ABSSSIs who could mostly benefit from a treatment with dalbavancin and agrees that the design of homogenous and robust studies would allow a broader use of dalbavancin even in other clinical settings.
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http://dx.doi.org/10.1080/14787210.2021.1894130DOI Listing
March 2021

Molecular Epidemiological Investigation of a Nosocomial Cluster of : Evidence of Recent Emergence in Italy and Ease of Transmission during the COVID-19 Pandemic.

J Fungi (Basel) 2021 Feb 15;7(2). Epub 2021 Feb 15.

Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, 16132 Genoa, Italy.

is an emerging MDR pathogen raising major concerns worldwide. In Italy, it was first and only identified in July 2019 in our hospital (San Martino Hospital, Genoa), where infection or colonization cases have been increasingly recognized during the following months. To gain insights into the introduction, transmission dynamics, and resistance traits of this fungal pathogen, consecutive isolates collected from July 2019 to May 2020 ( = 10) were subjected to whole-genome sequencing (WGS) and antifungal susceptibility testing (AST); patients' clinical and trace data were also collected. WGS resolved all isolates within the genetic clade I (South Asian) and showed that all but one were part of a cluster likely stemming from the index case. Phylogenetic molecular clock analyses predicted a recent introduction (May 2019) in the hospital setting and suggested that most transmissions were associated with a ward converted to a COVID-19-dedicated ICU during the pandemic. All isolates were resistant to amphotericin B, voriconazole, and fluconazole at high-level, owing to mutations in (K143R) and (A640V). Present data demonstrated that the introduction of MDR in Italy was a recent event and suggested that its spread could have been facilitated by the COVID-19 pandemic. Continued efforts to implement stringent infection prevention and control strategies are warranted to limit the spread of this emerging pathogen within the healthcare system.
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http://dx.doi.org/10.3390/jof7020140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919374PMC
February 2021
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