Fabrizio Taglietti

Verified @inmi.it

Medical doctor Internal Medicine and Infectious Disease specialist
IRCCS Lazzaro Spallanzani

RESEARCH INTERESTS

Internal Medicine, Infectious Disease

52

Scopus Publications

Scopus Publications

  • Tackling Acinetobacter baumannii
    Guido Granata, Fabrizio Taglietti, and Nicola Petrosillo

    MDPI AG
    Globally, multidrug-resistant (MDR) bacteria represent a menace to public health [...]

  • Streptococcus intermedius Brain Abscess with Lung Abscess and Aortic Valve Endocarditis: A Case Report and Literature Review
    Francesca Gavaruzzi, Pierangelo Chinello, Giuseppe Cucinotta, Gianluigi Oliva, Alessandro Capone, Guido Granata, Samir Al Moghazi, Emanuela Caraffa, and Fabrizio Taglietti

    MDPI AG
    Streptococcus intermedius is frequently associated with brain and liver abscesses, while pleuropulmonary infections are considered rarer. Even less frequent is the association of lung and brain abscesses due to this agent with infective endocarditis. We describe the case of a 40-year-old man complaining of cough, fever, and headache who was diagnosed with a brain abscess due to S. intermedius, a concomitant lung abscess, and aortic native valve endocarditis. He was treated with surgical drainage of the brain abscess and a 4-week course of intravenous ceftriaxone, followed by oral amoxicillin/clavulanate, obtaining healing of the lesions without relapse of the infection.

  • Clostridioides difficile and Enterococci’s Interplay in the Human Gut: Bacterial Alliance or Competition? A Systematic Literature Review
    Guido Granata, Francesco Schiavone, Fabrizio Taglietti, and Nicola Petrosillo

    MDPI AG
    Clostridioides difficile and Enterococcus spp. are two common bacterial pathogens populating the human microbiota. We possess scant data on how Clostridioides difficile interacts with Enterococcus spp. in the gut microbiota in subjects colonized with Clostridioides difficile or during a Clostridioides difficile infection. We carried out a systematic review of studies on Enterococcus spp. and Clostridioides difficile’s interaction in the gut microbiota and on the effect of Enterococcus spp. gut colonization on CDI development. Studies on Enterococcus spp. and Clostridioides difficile’s interaction in the gut microbiota and on the effect of Enterococcus spp. gut colonization on CDI were searched using the search terms “clostridium”, “clostridioides”, “difficile” and “enterococcus” on the MEDLINE and SCOPUS databases. PubMed was searched until 1 May 2023. An English language restriction was applied. The risk of bias in the included studies was not assessed. Quantitative and qualitative information was summarized in textual descriptions. Fourteen studies, published from August 2012 to November 2022, on Clostridioides difficile and Enterococcus spp.’s interaction in the gut microbiota met the inclusion criteria. The studies included in our systematic review reported evidence that the Enterococcus spp. intestinal burden represents a risk factor for the occurrence of CDI. There is supporting evidence that Enterococcus spp. play a role in CDI development and clinical outcomes.

  • Evolution of SARS-CoV-2 variants of concern over a period of Delta and Omicron cocirculation, among patients hospitalized for COVID-19 in an Italian reference hospital: Impact on clinical outcomes
    Annalisa Mondi, Ilaria Mastrorosa, Pierluca Piselli, Claudia Cimaglia, Giulia Matusali, Fabrizio Carletti, Giuseppina Giannico, Eugenia Milozzi, Elisa Biliotti, Silvia Di Bari,et al.

    Wiley
    AbstractDespite the higher transmissibility of Omicron Variant of Concern (VOC), several reports have suggested lower risk for hospitalization and severe outcomes compared to previous variants of SARS‐CoV‐2. This study, enrolling all COVID‐19 adults admitted to a reference hospital who underwent both the S‐gene‐target‐failure test and VOC identification by Sanger sequencing, aimed to describe the evolving prevalence of Delta and Omicron variants and to compare the main in‐hospital outcomes of severity, during a trimester (December 2021 to March 2022) of VOCs' cocirculation. Factors associated with clinical progression to noninvasive ventilation (NIV)/mechanical ventilation (MV)/death within 10 days and to MV/admission to intensive care unit (ICU)/death within 28 days, were investigated through multivariable logistic regressions. Overall, VOCs were: Delta n = 130/428, Omicron n = 298/428 (sublineages BA.1 n = 275 and BA.2 n = 23). Until mid‐February, Delta predominance shifted to BA.1, which was gradually displaced by BA.2 until mid‐March. Participants with Omicron VOC were more likely to be older, fully vaccinated, with multiple comorbidities and to have a shorter time from symptoms' onset, and less likely to have systemic symptoms and respiratory complications. Although the need of NIV within 10 days and MV within 28 days from hospitalization and the admission to ICU were less frequent for patients with Omicron compared to those with Delta infections, mortality was similar between the two VOCs. In the adjusted analysis, multiple comorbidities and a longer time from symptoms' onset predicted 10‐day clinical progression, while complete vaccination halved the risk. Multimorbidity was the only risk factor associated with 28‐day clinical progression. In our population, in the first trimester of 2022, Omicron rapidly displaced Delta in COVID‐19 hospitalized adults. Clinical profile and presentation differed between the two VOCs and, although Omicron infections showed a less severe clinical picture, no substantial differences for clinical progression were found. This finding suggests that any hospitalization, especially in more vulnerable individuals, may be at risk for severe progression, which is more related to the underlying frailty of patients than to the intrinsic severity of the viral variant.

  • Epidemiology of ventilator-associated pneumonia in ICU COVID-19 patients: an alarming high rate of multidrug-resistant bacteria
    Nardi Tetaj, Alessandro Capone, Giulia Valeria Stazi, Maria Cristina Marini, Gabriele Garotto, Donatella Busso, Silvana Scarcia, Ilaria Caravella, Manuela Macchione, Giada De Angelis,et al.

    Springer Science and Business Media LLC
    Abstract Background COVID‑19 is a novel cause of acute respiratory distress syndrome (ARDS) that leads patients to intensive care unit (ICU) admission requiring invasive ventilation, who consequently are at risk of developing of ventilator‑associated pneumonia (VAP). The aim of this study was to assess the incidence, antimicrobial resistance, risk factors, and outcome of VAP in ICU COVID-19 patients in invasive mechanical ventilation (MV). Methods Observational prospective study including adult ICU admissions between January 1, 2021, and June 31, 2021, with confirmed COVID-19 diagnosis were recorded daily, including demographics, medical history, ICU clinical data, etiology of VAPs, and the outcome. The diagnosis of VAP was based on multi-criteria decision analysis which included a combination of radiological, clinical, and microbiological criteria in ICU patients in MV for at least 48 h. Results Two hundred eighty-four COVID-19 patients in MV were admitted in ICU. Ninety-four patients (33%) had VAP during the ICU stay, of which 85 had a single episode of VAP and 9 multiple episodes. The median time of onset of VAP from intubation were 8 days (IQR, 5–13). The overall incidence of VAP was of 13.48 episodes per 1000 days in MV. The main etiological agent was Pseudomonas aeruginosa (39.8% of all VAPs) followed by Klebsiella spp. (16.5%); of them, 41.4% and 17.6% were carbapenem resistant, respectively. Patients during the mechanical ventilation in orotracheal intubation (OTI) had a higher incidence than those in tracheostomy, 16.46 and 9.8 episodes per 1000-MV day, respectively. An increased risk of VAP was reported in patients receiving blood transfusion (OR 2.13, 95% CI 1.26–3.59, p = 0.005) or therapy with Tocilizumab/Sarilumab (OR 2.08, 95% CI 1.12–3.84, p = 0.02). The pronation and PaO2/FiO2 ratio at ICU admission were not significantly associated with the development of VAPs. Furthermore, VAP episodes did not increase the risk of death in ICU COVID-19 patients. Conclusions COVID-19 patients have a higher incidence of VAP compared to the general ICU population, but it is similar to that of ICU ARDS patients in the pre-COVID-19 period. Interleukin-6 inhibitors and blood transfusions may increase the risk of VAP. The widespread use of empirical antibiotics in these patients should be avoided to reduce the selecting pressure on the growth of multidrug-resistant bacteria by implementing infection control measures and antimicrobial stewardship programs even before ICU admission.

  • Antibiotics Use in COVID-19 Patients: A Systematic Literature Review
    Guido Granata, Francesco Schiavone, Giuseppe Pipitone, Fabrizio Taglietti, and Nicola Petrosillo

    MDPI AG
    The issue of bacterial infections in COVID-19 patients has received increasing attention among scientists. Antibiotics were widely prescribed during the early phase of the pandemic. We performed a literature review to assess the reasons, evidence and practices on the use of antibiotics in COVID-19 in- and outpatients. Published articles providing data on antibiotics use in COVID-19 patients were identified through computerized literature searches on the MEDLINE and SCOPUS databases. Searching the MEDLINE database, the following search terms were adopted: ((antibiotic) AND (COVID-19)). Searching the SCOPUS database, the following search terms were used: ((antibiotic treatment) AND (COVID-19)). The risk of bias in the included studies was not assessed. Both quantitative and qualitative information were summarized by means of textual descriptions. Five-hundred-ninety-three studies were identified, published from January 2020 to 30 October 2022. Thirty-six studies were included in this systematic review. Of the 36 included studies, 32 studies were on the use of antibiotics in COVID-19 inpatients and 4 on antibiotic use in COVID-19 outpatients. Apart from the studies identified and included in the review, the main recommendations on antibiotic treatment from 5 guidelines for the clinical management of COVID-19 were also summarized in a separate paragraph. Antibiotics should not be prescribed during COVID-19 unless there is a strong clinical suspicion of bacterial coinfection or superinfection.

  • Telemedicine During COVID-19 Pandemic: Lesson Learned from the Lazio Region Infectious Diseases and Emergency Department Network
    Gaetano Maffongelli, Nazario Bevilacqua, Serena Vita, Tommaso Ascoli Bartoli, Angela Corpolongo, Domenico Benvenuto, Tiziana Chiriaco, Giuseppe Spiga, Sergio Ribaldi, Valentina Zirretta,et al.

    Springer Science and Business Media LLC
    AbstractTelemedicine and teleconsultation can be powerful and useful tools for patients to hamper the physical barriers to access to health care services during COVID-19 pandemic. We describe the teleconsultation (TC) model in the Lazio Region. It uses a hub-and-spoke network system on geographic regional basis using a web based digital platform, termed ADVICE with the aim to connect regional Emergency Departments (EDs) and Infectious Diseases (ID) acute and critical care settings for patients with acute ID syndrome. Between January 2020 and June 2021, the ADVICE platform received 18.686 TCs: of them, 10838 requests (58%) were for ID TCs in 7996 patients, followed by 2555(13%) requests for trauma, 2286(12%) for acute complex syndrome and 1681 (8%) for Stroke TCs. Three quarter of ID TCs were requested for SARS-COV-2 infection, followed by sepsis management in 7% and tuberculosis in 6%. In 5416 TCs, 68%, diagnostic investigations and therapeutic prescriptions were recommended before admission, in 1941 TCs, 24%, the recommendation was patient admission and in 608 TCs, 7%, was to discharge patient at home. Telemedicine have ensured high-profile consultations for ID patients and during COVID-19 the use of this resource optimized clinical patient management.

  • Proteomic analysis identifies a signature of disease severity in the plasma of COVID-19 pneumonia patients associated to neutrophil, platelet and complement activation
    Fabiola Ciccosanti, Manuela Antonioli, Alessandra Sacchi, Stefania Notari, Anna Farina, Alessia Beccacece, Marisa Fusto, Alessandra Vergori, Gianpiero D’Offizi, Fabrizio Taglietti,et al.

    Springer Science and Business Media LLC
    AbstractMost patients infected with SARS-CoV-2 display mild symptoms with good prognosis, while 20% of patients suffer from severe viral pneumonia and up to 5% may require intensive care unit (ICU) admission due to severe acute respiratory syndrome, which could be accompanied by multiorgan failure.Plasma proteomics provide valuable and unbiased information about disease progression and therapeutic candidates. Recent proteomic studies have identified molecular changes in plasma of COVID-19 patients that implied significant dysregulation of several aspects of the inflammatory response accompanied by a general metabolic suppression. However, which of these plasma alterations are associated with disease severity remains only partly characterized.A known limitation of proteomic studies of plasma samples is the large difference in the macromolecule abundance, with concentration spanning at least 10 orders of magnitude. To improve the coverage of plasma contents, we performed a deep proteomic analysis of plasma from 10 COVID-19 patients with severe/fatal pneumonia compared to 10 COVID-19 patients with pneumonia who did not require ICU admission (non-ICU). To this aim, plasma samples were first depleted of the most abundant proteins, trypsin digested and peptides subjected to a high pH reversed-phase peptide fractionation before LC–MS analysis.These results highlighted an increase of proteins involved in neutrophil and platelet activity and acute phase response, which is significantly higher in severe/fatal COVID-19 patients when compared to non-ICU ones. Importantly, these changes are associated with a selective induction of complement cascade factors in severe/fatal COVID-19 patients. Data are available via ProteomeXchange with identifier PXD036491. Among these alterations, we confirmed by ELISA that higher levels of the neutrophil granule proteins DEFA3 and LCN2 are present in COVID-19 patients requiring ICU admission when compared to non-ICU and healthy donors.Altogether, our study provided an in-depth view of plasma proteome changes that occur in COVID-19 patients in relation to disease severity, which can be helpful to identify therapeutic strategies to improve the disease outcome.

  • Timing and Outcomes of Noninvasive Ventilation in 307 ARDS COVID-19 Patients: An Observational Study in an Italian Third Level COVID-19 Hospital
    Nardi Tetaj, Pierluca Piselli, Sara Zito, Giada De Angelis, Maria Cristina Marini, Dorotea Rubino, Ilaria Gaviano, Maria Vittoria Antonica, Elisabetta Agostini, Candido Porcelli,et al.

    MDPI AG
    Background and Objectives: Background: Coronavirus disease 2019 (COVID-19) is a novel cause of Acute Respiratory Distress Syndrome (ARDS). Noninvasive ventilation (NIV) is widely used in patients with ARDS across several etiologies. Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, its use has grown significantly in hospital wards. However, there is a lack of evidence to support the efficacy of NIV in patients with COVID-19 ARDS. Materials and Methods: We conducted an observational cohort study including adult ARDS COVID-19 patients admitted in a third level COVID-center in Rome, Italy. The study analyzed the rate of NIV failure defined by the occurrence of orotracheal intubation and/or death within 28 days from starting NIV, its effectiveness, and the associated relative risk of death. The factors associated with the outcomes were identified through logistic regression analysis. Results: During the study period, a total of 942 COVID-19 patients were admitted to our hospital, of which 307 (32.5%) presented with ARDS at hospitalization. During hospitalization 224 (23.8%) were treated with NIV. NIV failure occurred in 84 (37.5%) patients. At 28 days from starting NIV, moderate and severe ARDS had five-fold and twenty-fold independent increased risk of NIV failure (adjusted odds ratio, aOR = 5.01, 95% CI 2.08–12.09, and 19.95, 95% CI 5.31–74.94), respectively, compared to patients with mild ARDS. A total of 128 patients (13.5%) were admitted to the Intensive Care Unit (ICU). At 28-day from ICU admission, intubated COVID-19 patients treated with early NIV had 40% lower mortality (aOR 0.60, 95% CI 0.25–1.46, p = 0.010) compared with patients that underwent orotracheal intubation without prior NIV. Conclusions: These findings show that NIV failure was independently correlated with the severity category of COVID-19 ARDS. The start of NIV in COVID-19 patients with mild ARDS (P/F > 200 mmHg) appears to increase NIV effectiveness and reduce the risk of orotracheal intubation and/or death. Moreover, early NIV (P/F > 200 mmHg) treatment seems to reduce the risk of ICU mortality at 28 days from ICU admission.

  • Durlobactam in the Treatment of Multidrug-Resistant Acinetobacter baumannii Infections: A Systematic Review
    Guido Granata, Fabrizio Taglietti, Francesco Schiavone, and Nicola Petrosillo

    MDPI AG
    A. baumannii is a frequent cause of difficult-to-treat healthcare-associated infections. The use of a novel beta-lactamase inhibitor, durlobactam, has been proposed against multidrug-resistant A. baumannii. A systematic review of studies assessing the efficacy and safety of durlobactam in the treatment of multidrug-resistant A. baumannii infections was carried out. The study protocol was pre-registered on PROSPERO (CRD42022311723). Published articles on durlobactam were identified through computerized literature searches with the search terms “durlobactam” and “ETX2514” using PubMed. PubMed was searched until 15 February 2022. Articles providing data on the main characteristics of durlobactam and on the efficacy and safety of durlobactam in the treatment of A. baumannii infections were included in this systematic review. Attempt was made to obtain information about unpublished studies. English language restriction was applied. The risk of bias in the included studies was not assessed. Both quantitative and qualitative information were summarized by means of textual descriptions. Thirty studies on durlobactam were identified, published from June 2017 to November 2020. Sixteen studies met the inclusion criteria. Durlobactam is effective against A. baumannii when used in combination with sulbactam. Future clinical trials are needed to confirm the possibility to treat infections caused by multidrug-resistant A. baumannii with this combination.

  • Epidemiology, Clinical Presentation and Treatment of Non-Hepatic Hyperammonemia in ICU COVID-19 Patients
    Nardi Tetaj, Giulia Valeria Stazi, Maria Cristina Marini, Gabriele Garotto, Donatella Busso, Silvana Scarcia, Ilaria Caravella, Manuela Macchione, Giada De Angelis, Rachele Di Lorenzo,et al.

    MDPI AG
    (1) Background: Although COVID-19 is largely a respiratory disease, it is actually a systemic disease that has a wide range of effects that are not yet fully known. The aim of this study was to determine the incidence, predictors and outcome of non-hepatic hyperammonemia (NHH) in COVID-19 in intensive care unit (ICU); (2) Methods: This is a 3-month prospective observational study in a third-level COVID-19 hospital. The authors collected demographic, clinical, severity score and outcome data. Logistic regression analyses were performed to identify predictors of NHH; (3) Results: 156 COVID-19 patients were admitted to the ICU. The incidence of NHH was 12.2% (19 patients). The univariate analysis showed that invasive mechanical ventilation had a 6.6-fold higher risk (OR 6.66, 95% CI 0.86–51.6, p = 0.039) for NHH, while in the multiple regression analysis, there was a 7-fold higher risk for NHH—but it was not statistically significant (OR 7.1, 95% CI 0.90–56.4, p = 0.062). Demographics, clinical characteristics and mortality in the ICU at 28 days did not show a significant association with NHH. (4) Conclusions: The incidence of NHH in ICU COVID-19 patients was not low. NHH did not appear to significantly increase mortality, and all patients with non-hepatic hyperammonemia were successfully treated without further complications. However, the pathogenesis of NHH in ICU patients with COVID-19 remains a topic to be explored with further research.

  • Characteristics and Outcomes of COVID-19-Related Hospitalization among PLWH
    Roberta Gagliardini, Alessandra Vergori, Patrizia Lorenzini, Stefania Cicalini, Carmela Pinnetti, Valentina Mazzotta, Annalisa Mondi, Ilaria Mastrorosa, Marta Camici, Simone Lanini,et al.

    MDPI AG
    Background: There is conflicting evidence for how HIV influences COVID-19 infection. The aim of this study was to compare characteristics at presentation and the clinical outcomes of people living with HIV (PLWH) versus HIV-negative patients (non-PLWH) hospitalized with COVID-19. Methods: Primary endpoint: time until invasive ventilation/death. Secondary endpoints: time until ventilation/death, time until symptoms resolution. Results: A total of 1647 hospitalized patients were included (43 (2.6%) PLWH, 1604 non-PLWH). PLWH were younger (55 vs. 61 years) and less likely to be with PaO2/FiO2 < 300 mmHg compared with non-PLWH. Among PLWH, nadir of CD4 was 185 (75–322) cells/μL; CD4 at COVID-19 diagnosis was 272 cells/μL (127–468) and 77% of these were virologically suppressed. The cumulative probability of invasive mechanical ventilation/death at day 15 was 4.7% (95%CI 1.2–17.3) in PLWH versus 18.9% (16.9–21.1) in non-PLWH (p = 0.023). The cumulative probability of non-invasive/invasive ventilation/death at day 15 was 20.9% (11.5–36.4) in PLWH versus 37.6% (35.1–40.2) in non-PLWH (p = 0.044). The adjusted hazard ratio (aHR) of invasive mechanical ventilation/death of PLWH was 0.49 (95% CI 0.12–1.96, p = 0.310) versus non-PLWH; similarly, aHR of non-invasive/invasive ventilation/death of PLWH was 1.03 (95% CI 0.53–2.00, p = 0.926). Conclusion: A less-severe presentation of COVID-19 at hospitalization was observed in PLWH compared to non-PLWH; no difference in clinical outcomes could be detected.

  • Vaccine-Induced Subacute Thyroiditis (De Quervain’s) after mRNA Vaccine against SARS-CoV-2: A Case Report and Systematic Review
    Giuseppe Pipitone, Lorenzo Vittorio Rindi, Nicola Petrosillo, Nunzio Adalberto Maria Foti, Grazia Caci, Chiara Iaria, Davide Roberto Donno, Evangelo Boumis, Giuseppe Paviglianiti, and Fabrizio Taglietti

    MDPI AG
    De Quervain’s thyroiditis, sometimes referred to as subacute thyroiditis (SAT), is the most common granulomatous disease of the thyroid, typically found after a viral infection in middle-aged women. The mRNA encoding for the angiotensin-converting enzyme-2 (ACE-2) receptor is expressed in follicular thyroid cells, making them a potential target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Besides infection, SARS-CoV-2 vaccines have also been implicated in SAT pathogenesis. We present a case of a woman developing SAT following vaccination with Comirnaty by Pfizer Inc. (New-York, USA). We performed a systematic review of similar cases available in the literature to provide a better understanding of the topic. We searched the databases PubMed and Embase and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Patient records were then sorted according to the type of administered vaccine and a statistical analysis of the extracted data was performed. No statistically significant difference between mRNA vaccines and other vaccines in inducing SAT was found, nor was any found in terms of patient demographics, symptoms at presentation, initial, or follow-up blood tests. In our case report, we described the possible association between SARS-CoV-2 mRNA-based vaccine Comirnaty and SAT.

  • Giant cell arteritis after COVID-19 vaccination/disease: suggestions for further shots?
    Pierangelo Chinello, Francesca Gavaruzzi, Anna Chiara Epifani, and Fabrizio Taglietti

    SAGE Publications
    Sirs, We read with great interest the article of Gabrielli and coll. describing a case of giant cell arteritis (GCA) after COVID-19 mRNA vaccine and COVID-19 asymptomatic infection, since we had the opportunity to visit such a patient at our Institution. Different infectious agents have been suggested to be involved in the pathogenesis of GCA, including VaricellaZoster Virus, Epstein Barr Virus, Parvovirus B19 and Chlamydia pneumoniae; more recently, the role of SARSCoV-2 is also under investigation. Several cases of GCA in SARS-CoV-2 infected patients have been described (Table 1). COVID-19 is known for its immune dysregulation and a strong association between interleukins and rheumatic diseases was found during the COVID-19 pandemic: for example, IL-6 and IL-17 showed association between polymyalgia rheumatica (PMR) and arthritis among COVID-19 patients. Oda et al. reported a case of adult large vessel vasculitis after SARS-CoV-2 infection and hypothesised, after a previous report on endothelial cell infection and endotheliitis in patients with COVID-19, that this infection and endotheliitis could have led to vasculitis. Furthermore, cases of aortitis linked to SARS-CoV-2 infection have been described. Cases of GCA following SARS-CoV-2 vaccination have also been reported (Table 1). In a pharmacovigilance study using VigiBase, among 2,499,457 spontaneous reports with mRNA COVID-19 vaccines Mettler et al. identified 2125 vasculitis cases (8.5 per 10,000 reports), of which 501 were GCA. However, not only mRNA vaccines have been proposed to be linked to GCA: in a previous report, Mettler at al. observed among 1,295,482 reports concerning COVID-19 vaccines 147 GCA cases, 290 PMR cases and 9 cases of GCA with PMR; cases reported after mRNA vaccine were 61.9% and after viral vector vaccine were 37.4% of the total. Which could be the mechanisms of post-vaccinal GCA? Liozon et al. reported 10 cases of post-influenza vaccine GCA and reviewed other cases from the literature. Their conclusion was that the onset of GCA or PMR postinfluenza vaccine is not exceptional and may be a serious form of autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome), especially in people with personal or familial risk of GCA/PMR. ASIA syndrome is thought to be triggered by the adjuvants of the vaccines. However, mRNA SARS-CoV-2 vaccines are considered essentially adjuvant free, but they can themselves stimulate innate immunity with activation of Toll-like receptors (TLRs), notably TLR-7 and TLR-9, which may trigger an autoimmune response. At the end of their work, the Authors state that they continue to encourage COVID-19 vaccination because the benefits of vaccination far outweigh any theorical risk of immune dysregulation following administration. We agree with them from a general point of view; however, in this particular patient a synergy between the vaccine immunological stimulation and the subsequent immunological stimulation by the infection could have contributed to the development of GCA. Therefore, we suggest that the need and the advisability of further anti-SARS-CoV-2 vaccine shots should be carefully evaluated for this relatively young patient, taking into account the balance between benefits and risks.

  • Post-mortem differential diagnosis from COVID-19: A case of fulminant myocarditis HHV-6 related
    Daniele Colombo, Camilla Cecannecchia, Marco Albore, Fabrizio Taglietti, Roberta Nardacci, Giorgio Bolino, and Franca Del Nonno

    Wiley
    To the Editor, Human herpesvirus 6 (HHV‐6), a T‐cell lymphotropic virus, is the sixth recognized member belonging to the Herpesviridae family and has been identified as the etiologic agent of exanthem subitum (Zahorsky's disease, sixth disease, and roseola infantum), a common childhood disease. HHV‐6 infection can reactivate in immunocompromised or in immunocompetent adults and may cause encephalitis, interstitial pneumonia, and myocarditis with a high mortality rate, especially in fragile patients, although these effects occurred less frequently in immunocompetent hosts. Fulminant myocarditis is an acute inflammation of the myocardium that could manifest itself with unspecific symptoms like fatigue and shortness of breath or chest discomfort. Therefore, the diagnosis and treatment are often delayed with a worse prognosis. Many viruses can cause fulminant myocarditis, including Coxsackievirus B, adenoviruses, parvovirus B19, Epstein–Barr virus (EBV), cytomegalovirus (CMV), HHV 6 and, more recently, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Here, we report a fatal case of HHV‐6‐related fulminant myocarditis with interstitial pneumonia and necrotizing vasculitis in an immunocompetent adult. A 59‐year‐old man was admitted to the hospital for fever and dyspnea for 3 days, resistant to therapy with antibiotic and antipyretic. His medical history showed hypertension and obesity. At admission, the clinical examination revealed: temperature of 37.7°C, heart rate of 115/min, blood pressure of 120/85mmHg, oxygen saturation 93%, bilateral decreased breath sounds, and lower right leg reddened. Standard hematologic tests and blood chemistries showed increased levels of c‐reactive protein (CRP), white blood cell count of 14 100/μL with neutrophilia, lymphocytopenia, and thrombocytopenia, elevated levels of troponin (115 06 ng/L), transaminase, and bilirubin. Chest computed tomography showed: parenchymal thickenings with aerial bronchogram localized on the right lung's apex and middle lobe, diffuse and bilateral "ground glass" areas, pleural and pericardial effusions, and lymphadenopathy. That nonspecific clinical picture was compatible with different viral infections, including COVID‐19. However, the patient presented two nasopharyngeal swabs negative for SARS‐CoV‐2. The following day the fever was down but the oxygen saturation was still lower than normal. An electrocardiogram showed sinus tachycardia and echocardiogram confirmed the pericardial effusion without signs of cardiac tamponade and revealed an ejection fraction of 60%. On the third‐day blood chemistries confirmed the neutrophilic leucocytosis and showed a further increase of aspartate aminotransferase (133U/L), alanine aminotransferase (205U/L), and high D‐dimer level (3446 ng/mL). During the same day, the patient suddenly died of cardiac arrest. During the short hospitalization, the patient was treated with antibiotics (clarithromycin, ceftriaxone, and hydroxychloroquine) and heparin. To determine the cause of death a complete post‐mortem examination was performed at the INMI L. Spallanzani‐IRCCS Hospital (Rome, Italy). The study was approved by the local ethics committee (Ethics Committee approval number 9/2020). Whole body post‐mortem examination was performed according to guidance for post‐mortem and collection and submission of specimens and biosafety practices, to reduce the risk of transmission of infectious pathogens during and after the post‐mortem examination. Since SARS‐CoV‐2 is classified as a BSL3 organism, specific operating procedures for BSL3 pathogens were followed. Autopsies were performed in a specific COVID‐19 designated autopsy room with airflow control and airborne infection control procedures including use of appropriated PPE (i.e., NIOSH‐certified disposable N‐95 respirator). Macroscopic findings revealed pleural effusion (about 250 and 500mL respectively on the left and the right) and pericardial (500mL) reddish‐tinted fluids, typically due to blood effusion. Lungs were significantly increased in volume and consistency with diffuse pleural thickening; cut surface showed consolidation of lobes and red congested areas. Bronchi were dilated and pulmonary vasculature showed no blood clots or local thrombosis. The heart showed increased size and weight (500 g) with

  • Incidence of pneumothorax and pneumomediastinum in 497 covid-19 patients with moderate–severe ards over a year of the pandemic: An observational study in an italian third level covid-19 hospital
    Nardi Tetaj, Gabriele Garotto, Fabrizio Albarello, Annelisa Mastrobattista, Micaela Maritti, Giulia Valeria Stazi, Maria Cristina Marini, Ilaria Caravella, Manuela Macchione, Giada De Angelis,et al.

    MDPI AG
    (1) Background: COVID-19 is a novel cause of acute respiratory distress syndrome (ARDS). Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, there has also been an increase in the incidence of cases with pneumothorax (PNX) and pneumomediastinum (PNM). However, the incidence and the predictors of PNX/PMN in these patients are currently unclear and even conflicting. (2) Methods: The present observational study analyzed the incidence of barotrauma (PNX/PNM) in COVID-19 patients with moderate–severe ARDS hospitalized in a year of the pandemic, also focusing on the three waves occurring during the year, and treated with positive-pressure ventilation (PPV). We collected demographic and clinical data. (3) Results: During this period, 40 patients developed PNX/PNM. The overall incidence of barotrauma in all COVID-19 patients hospitalized in a year was 1.6%, and in those with moderate–severe ARDS in PPV was 7.2% and 3.8 events per 1000 positive-pressure ventilator days. The incidence of barotrauma in moderate–severe ARDS COVID-19 patients during the three waves was 7.8%, 7.4%, and 8.7%, respectively. Treatment with noninvasive respiratory support alone was associated with an incidence of barotrauma of 9.1% and 2.6 events per 1000 noninvasive ventilator days, of which 95% were admitted to the ICU after the event, due to a worsening of respiratory parameters. The incidence of barotrauma of ICU COVID-19 patients in invasive ventilation over a year was 5.8% and 2.7 events per 1000 invasive ventilator days. There was no significant difference in demographics and clinical features between the barotrauma and non-barotrauma group. The mortality was higher in the barotrauma group (17 patients died, 47.2%) than in the non-barotrauma group (170 patients died, 37%), although this difference was not statistically significant (p = 0.429). (4) Conclusions: The incidence of PNX/PNM in moderate–severe ARDS COVID-19 patients did not differ significantly between the three waves over a year, and does not appear to be very different from that in ARDS patients in the pre-COVID era. The barotrauma does not appear to significantly increase mortality in COVID-19 patients with moderate–severe ARDS if protective ventilation strategies are applied. Attention should be paid to the risk of barotrauma in COVID-19 patients in noninvasive ventilation because the event increases the probability of admission to the intensive care unit (ICU) and intubation.

  • Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial (Journal of Translational Medicine, (2020), 18, 1, (405), 10.1186/s12967-020-02573-9)
    Francesco Perrone, Maria Carmela Piccirillo, Paolo Antonio Ascierto, Carlo Salvarani, Roberto Parrella, Anna Maria Marata, Patrizia Popoli, Laurenzia Ferraris, Massimiliano M. Marrocco-Trischitta, Diego Ripamonti,et al.

    Springer Science and Business Media LLC
    Francesco Perrone , Maria Carmela Piccirillo, Paolo Antonio Ascierto, Carlo Salvarani, Roberto Parrella, Anna Maria Marata, Patrizia Popoli, Laurenzia Ferraris, Massimiliano M. Marrocco‐Trischitta, Diego Ripamonti, Francesca Binda, Paolo Bonfanti, Nicola Squillace, Francesco Castelli, Maria Lorenza Muiesan, Miriam Lichtner, Carlo Calzetti, Nicola Duccio Salerno, Luigi Atripaldi, Marco Cascella, Massimo Costantini, Giovanni Dolci, Nicola Cosimo Facciolongo, Fiorentino Fraganza, Marco Massari, Vincenzo Montesarchio, Cristina Mussini, Emanuele Alberto Negri, Gerardo Botti, Claudia Cardone, Piera Gargiulo, Adriano Gravina, Clorinda Schettino, Laura Arenare, Paolo Chiodini and Ciro Gallo on behalf of the TOCIVID‐19 investigators, Italy

  • Prophylactic heparin and risk of orotracheal intubation or death in patients with mild or moderate COVID-19 pneumonia
    Alessandra Vergori, , Patrizia Lorenzini, Alessandro Cozzi-Lepri, Davide Roberto Donno, Gina Gualano, Emanuele Nicastri, Fabio Iacomi, Luisa Marchioni, Paolo Campioni,et al.

    Springer Science and Business Media LLC
    AbstractProphylactic low molecular weight heparin (pLMWH) is currently recommended in COVID-19 to reduce the risk of coagulopathy. The aim of this study was to evaluate whether the antinflammatory effects of pLMWH could translate in lower rate of clinical progression in patients with COVID-19 pneumonia. Patients admitted to a COVID-hospital in Rome with SARS-CoV-2 infection and mild/moderate pneumonia were retrospectively evaluated. The primary endpoint was the time from hospital admission to orotracheal intubation/death (OTI/death). A total of 449 patients were included: 39% female, median age 63 (IQR, 50–77) years. The estimated probability of OTI/death for patients receiving pLMWH was: 9.5% (95% CI 3.2–26.4) by day 20 in those not receiving pLMWH vs. 10.4% (6.7–15.9) in those exposed to pLMWH; p-value = 0.144. This risk associated with the use of pLMWH appeared to vary by PaO2/FiO2 ratio: aHR 1.40 (95% CI 0.51–3.79) for patients with an admission PaO2/FiO2 ≤ 300 mmHg and 0.27 (0.03–2.18) for those with PaO2/FiO2 > 300 mmHg; p-value at interaction test 0.16. pLMWH does not seem to reduce the risk of OTI/death mild/moderate COVID-19 pneumonia, especially when respiratory function had already significantly deteriorated. Data from clinical trials comparing the effect of prophylactic vs. therapeutic dosage of LMWH at various stages of COVID-19 disease are needed.

  • No Efficacy of the Combination of Lopinavir/Ritonavir Plus Hydroxychloroquine Versus Standard of Care in Patients Hospitalized With COVID-19: A Non-Randomized Comparison
    Roberta Gagliardini, Alessandro Cozzi-Lepri, Andrea Mariano, Fabrizio Taglietti, Alessandra Vergori, Amina Abdeddaim, Francesco Di Gennaro, Valentina Mazzotta, Alessandra Amendola, Giampiero D’Offizi,et al.

    Frontiers Media SA
    Objectives: No specific treatment has been approved for COVID-19. Lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) have been used with poor results, and a trial showed advantages of combined antiviral therapy vs. single antivirals. The aim of the study was to assess the effectiveness of the combination of antivirals (LPV/r and HCQ) or their single use in COVID-19 hospitalized patients vs. standard of care (SoC).Methods: Patients ≥18 years with SARS-CoV-2 infection, defined as positive RT-PCR from nasal/oropharyngeal (NP/OP) swab or positive serology, admitted at L. Spallanzani Institute (Italy) were included.Primary endpoint: time to invasive ventilation/death. Secondary endpoint: time to two consecutive negative SARS-CoV-2 PCRs in NP/OP swabs. In order to control for measured confounders, a marginal Cox regression model with inverse probability weights was used.Results: A total of 590 patients were included in the analysis: 36.3% female, 64 years (IQR 51–76), and 91% with pneumonia. Cumulative probability of invasive ventilation/death at 14 days was 21.2% (95% CI 17.6, 24.7), without difference between SOC, LPV/r, hydroxychloroquine, HCQ + LPV/r, and SoC. The risk of invasive ventilation/death in the groups appeared to vary by baseline ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2). Overall cumulative probability of confirmed negative nasopharyngeal swabs at 14 days was 44.4% (95% CI 38.9, 49.9), without difference between groups.Conclusion: In this retrospective analysis, we found no difference in the rate of invasive ventilation/death or viral shedding by different strategies, as in randomized trials performed to date. Moreover, even the combination HCQ + LPV/r did not show advantages vs. SoC.

  • Risk and predictive factors of prolonged viral RNA shedding in upper respiratory specimens in a large cohort of COVID-19 patients admitted to an Italian reference hospital
    Annalisa Mondi, Patrizia Lorenzini, Concetta Castilletti, Roberta Gagliardini, Eleonora Lalle, Angela Corpolongo, Maria Beatrice Valli, Fabrizio Taglietti, Stefania Cicalini, Laura Loiacono,et al.

    Elsevier BV
    Background Few data about predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS) are available. Methods Retrospective study including all patients admitted with COVID-19 in an Italian reference hospital for infectious diseases between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between duration of VS and probability of clinical outcomes was evaluated through inverse probability weighted Cox model. Results 536 subjects were included. Median duration of VS from symptoms onset was 18 days (IQR 12-26). The estimated 30-day probability of VC was 70.2% (95%CI:65-75). At multivariable analysis, patients with comorbidities (aIRR = 0.88, p = 0.004), lymphopenia at hospital admission (aIRR = 0.75, p = 0.032) and with moderate/severe respiratory disease (aIRR = 0.42, p < 0.001) had a lower chance of achieving VC. The development of moderate/severe respiratory failure (aOR = 2.65, p = 0.003), a delayed hospital admission after symptoms onset (aOR = 1.18, p < 0.001), having baseline comorbidities (aOR = 1.25, p = 0.019) and D-dimer >1000 ng/mL at admission (aOR = 1.76, p = 0.035) independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery (aHR = 2.17, p < 0.001) and reduced the probability of death/mechanical ventilation (aHR = 0.36, p = 0.002). Conclusions In this study, severity of respiratory disease, comorbidities, delayed hospital admission and inflammatory markers negatively predicted the achievement of VC, which resulted to be associated to better clinical outcomes. These findings highlight the importance of prompt hospitalization of symptomatic patients, especially in presence of signs of severity or comorbidities.

  • COVID-19 pneumonia and pulmonary microembolism in a patient with B-thalassemia major
    Marco Marziali, Michela Ribersani, Anna Annunziata Losardo, Fabrizio Taglietti, Pellegrina Pugliese, Alessandra Micozzi, Giuseppe Gentile, and Antonio Angeloni

    Wiley
    We think that thalassemia is not necessarily a cause of aggravation of the clinical course in COVID‐19; however, certain key factors must be considered, such as the anemic condition, the likely pathogenic role of the virus on hemoglobin, and the hypercoagulable state to prevent any complications.

  • Salmonella hessarek gastroenteritis with bacteremia: A case report and literature review
    Pierangelo Chinello, Guido Granata, Vincenzo Galati, Fabrizio Taglietti, Simone Topino, Emanuela Caraffa, Carolina Venditti, Nazario Bevilacqua, Lucilla Sbardella, Stefano Bilei,et al.

    MDPI AG
    Salmonella enterica subspecies enterica serotype Hessarek (Salmonella Hessarek) is considered a serovar with high host specificity and is an uncommon cause of disease in humans; no cases of S. Hessarek bacteremia have been reported in humans to date. On 16 July 2019, a young male presented abdominal pain, vomit, diarrhea, and fever up to 41 °C, a few hours after a kebab meal containing goat meat; he went to the Emergency Room, where a Film Array® GI Panel (BioFire, Biomerieux Company, Marcy-L´Étoile, France) was performed on his feces and results were positive for Salmonella. The culture of the feces was negative, but the blood culture was positive for Salmonella spp., which was identified as Salmonella Hessarek by seroagglutination assays. The patient was treated with ceftriaxone 2 g intravenously qd for 8 days; he was discharged in good general conditions, and ciprofloxacin 500 mg per os bid for 7 more days was prescribed, after exclusion of endocarditis and of clinical signs of complicated bacteremia. This case of Salmonella Hessarek gastroenteritis with bacteremia is probably the first case of bloodstream human infection due to this agent ever described. Further studies are needed to ascertain the global burden of S. Hessarek disease in humans.

  • Preventing sepsis development in complicated urinary tract infections
    Nicola Petrosillo, Guido Granata, Breida Boyle, Maeve M. Doyle, Biagio Pinchera, and Fabrizio Taglietti

    Informa UK Limited
    ABSTRACT Introduction: Urinary tract infections (UTIs) are the most prevalent infections in the community and the most common reason for antimicrobial prescribing in ambulatory care. A UTI is defined as complicated when urinary tract anatomical abnormalities or urinary devices are present, when it is recurrent and when associated with immunodeficiency. Complicated UTIs (cUTIs) have a higher risk of treatment failure and often require longer antimicrobial treatment courses. cUTIs, especially those which are healthcare-associated, are often due to multidrug resistant organisms (MDROs). Areas covered: This article will review the available evidence in relation to prevention of sepsis in cUTI, evaluating the risk factors associated with sepsis development. Published articles from January 2005 to September 2019 on UTIs and sepsis prevention in complicated UTIs were identified by using MEDLINE (National Library of Medicine Bethesda MD) and by reviewing the references of retrieved articles. Expert opinion: Prevention of sepsis relies on prompt and timely diagnosis of cUTI, early identification of the causative organism, removal of obstructions and source control, proper and adequate empirical/targeted antimicrobial treatment. In particular, source control, i.e. removal of urinary obstructions, infected stents, urinary catheters, nephrostomies, and drainage of hydronephrosis/abscess, is essential for preventing the development and progression of sepsis.

  • Treatment options for colistin resistant klebsiella pneumoniae: Present and future
    Petrosillo, Taglietti, and Granata

    MDPI AG
    Multidrug-resistant (MDR) Klebsiella pneumoniae represents an increasing threat to human health, causing difficult-to-treat infections with a high mortality rate. Since colistin is one of the few treatment options for carbapenem-resistant K. pneumoniae infections, colistin resistance represents a challenge due to the limited range of potentially available effective antimicrobials, including tigecycline, gentamicin, fosfomycin and ceftazidime/avibactam. Moreover, the choice of these antimicrobials depends on their pharmacokinetics/pharmacodynamics properties, the site of infection and the susceptibility profile of the isolated strain, and is sometimes hampered by side effects. This review describes the features of colistin resistance in K. pneumoniae and the characteristics of the currently available antimicrobials for colistin-resistant MDR K. pneumoniae, as well as the characteristics of novel antimicrobial options, such as the soon-to-be commercially available plazomicin and cefiderocol. Finally, we consider the future use of innovative therapeutic strategies in development, including bacteriophages therapy and monoclonal antibodies.

  • Persistence of ZIKV-RNA in the cellular fraction of semen is accompanied by a surrogate-marker of viral replication. Diagnostic implications for sexual transmission