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Gentile I, Giuliano S, Corcione S, De Rosa FG, Falcone M, Giacobbe DR, Maraolo AE, Mastroianni CM, Oliva A, Pascale R, Tascini C, Tiseo G, Viale P, Bassetti M. Current role of ceftobiprole in the treatment of hospital-acquired and community-acquired pneumonia: expert opinion based on literature and real-life experiences. Expert Rev Anti Infect Ther 2025; 23:217-225. [PMID: 39882832 DOI: 10.1080/14787210.2025.2461552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/27/2025] [Accepted: 01/29/2025] [Indexed: 01/31/2025]
Abstract
INTRODUCTION Community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) are major global health challenges, with high morbidity and mortality rates. The increasing prevalence of multidrug-resistant (MDR) bacteria may diminish the effectiveness of standard empirical antibiotics, highlighting the need for broader-spectrum agents that target also MDR organisms. AREAS COVERED This review summarizes findings from a PubMed search on the use of ceftobiprole in CAP and HAP. It highlights key features of ceftobiprole, including its mechanism of action and broad spectrum of activity against multiple MDR pathogens. Clinical data from randomized controlled trials and real-world studies underscore its non-inferiority to standard treatments, with favorable safety profile and high clinical cure rates even in challenging cases. EXPERT OPINION Ceftobiprole represents a valid option for the patients with CAP and HAP. Its main advantages include its broad spectrum of activity, making it a valuable therapeutic choice for treating polymicrobial infections, and its favorable safety profile, which makes it a good candidate in elderly patients with multiple comorbidities and polypharmacy. Caution is advised in patients at high risk of ESBL-producing organisms or MDR Pseudomonas aeruginosa infections, where combination therapy is recommended. Moreover, therapeutic drug monitoring is recommended to improve outcomes, particularly in complex clinical conditions.
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Affiliation(s)
- Ivan Gentile
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | - Simone Giuliano
- Infectious Diseases Clinic, Azienda Sanitaria Universitaria del Friuli Centrale (ASUFC), Udine, Italy
| | - Silvia Corcione
- Infectious Diseases Unit, Department of Medical Sciences, University of Torino, Torino, Italy
| | | | - Marco Falcone
- Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Daniele Roberto Giacobbe
- Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
- Clinica Malattie Infettive, IRCCS Ospedale Policlinico, Genoa, Italy
| | - Alberto Enrico Maraolo
- Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy
| | | | - Alessandra Oliva
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Renato Pascale
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Carlo Tascini
- Infectious Diseases Clinic, Azienda Sanitaria Universitaria del Friuli Centrale (ASUFC), Udine, Italy
- Department of Medicine (DMED), University of Udine, Udine, Italy
| | - Giusy Tiseo
- Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Pisa, Italy
| | - Pierluigi Viale
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Bassetti
- Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
- Clinica Malattie Infettive, IRCCS Ospedale Policlinico, Genoa, Italy
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Doppalapudi S, Adrish M. Community-acquired pneumonia: The importance of the early detection of drug-resistant organisms. World J Crit Care Med 2024; 13:91314. [PMID: 38855277 PMCID: PMC11155498 DOI: 10.5492/wjccm.v13.i2.91314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 03/14/2024] [Accepted: 04/22/2024] [Indexed: 06/03/2024] Open
Abstract
Pneumonia is a disease associated with significant healthcare burden with over 1.5 million hospitalizations annually and is the eighth leading cause of death in the United States. While community-acquired pneumonia (CAP) is generally considered an acute time-limited illness, it is associated with high long-term mortality, with nearly one-third of patients requiring hospitalization dying within one year. An increasing trend of detecting multidrug-resistant (MDR) organisms causing CAP has been observed, especially in the Western world. In this editorial, we discuss about a publication by Jatteppanavar et al which reported that a case of a MDR organism was the culprit in developing pneumonia, bacteremia, and infective endocarditis that led to the patient's death. The early detection of these resistant organisms helps improve patient outcomes. Significant advances have been made in the biotechnological and research space, but preventive measures, diagnostic techniques, and treatment strategies need to be developed.
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Affiliation(s)
- Sai Doppalapudi
- Department of Medicine, Bronx Care Health System, New York Affiliated with The Icahn School of Medicine at Mount Sinai, Bronx, NY 10457, United States
| | - Muhammad Adrish
- Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, TX 77030, United States
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Campaña-Duel E, Camprubí-Rimblas M, Areny-Balagueró A, Quero S, Artigas A, Ceccato A. Risk of Multidrug-Resistant Pathogens in Severe Community-Acquired Pneumonia. Semin Respir Crit Care Med 2024; 45:246-254. [PMID: 38301713 DOI: 10.1055/s-0043-1778138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2024]
Abstract
Severe community-acquired pneumonia (SCAP) is difficult to treat when caused by difficult-to-treat (DTR) pathogens because of limited treatment options and poorer clinical outcomes. Over time, several predictive scoring systems based on risk factors for infection with multidrug resistant pathogens have been developed. We reviewed the available tools for identifying DTR pathogens as the cause of SCAP, both predictive scoring systems and rapid diagnostic methods, to develop management strategies aimed at early identification of DTR pathogens, reducing broad-spectrum antibiotic use and improving clinical outcomes. The scoring systems reviewed show considerable heterogeneity among them at the level of the region studied, the definition of risk factors, as well as which DTR pathogens are the target pathogens. The models described have shown limited effectiveness in reducing inappropriate antibiotic treatment or improving patient outcomes by themselves. However, predictive models could serve as a first step in identifying DTR pathogen infections as part of a larger detection algorithm. Rapid diagnostic tools, such as multiplex polymerase chain reaction, would be useful for the rapid identification of pneumonia-causing pathogens and their resistance mechanisms. In resource-limited settings, rapid tests should be limited to patients at high risk of developing SCAP due to DTR pathogens. We propose an integrative algorithm based on the different scores, taking into account local epidemiological data, where ideally each center should have an antimicrobial stewardship program.
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Affiliation(s)
- E Campaña-Duel
- Critical Care Center, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Sabadell, Spain
- Centro de Investigación Biomedica En Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Barcelona, Spain
| | - M Camprubí-Rimblas
- Critical Care Center, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Sabadell, Spain
- Centro de Investigación Biomedica En Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Barcelona, Spain
| | - A Areny-Balagueró
- Critical Care Center, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Sabadell, Spain
- Centro de Investigación Biomedica En Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Barcelona, Spain
| | - Sara Quero
- Critical Care Center, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Sabadell, Spain
- Centro de Investigación Biomedica En Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Barcelona, Spain
| | - A Artigas
- Critical Care Center, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Sabadell, Spain
- Centro de Investigación Biomedica En Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Barcelona, Spain
| | - Adrian Ceccato
- Critical Care Center, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Universitat Autònoma de Barcelona, Sabadell, Spain
- Centro de Investigación Biomedica En Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Barcelona, Spain
- Intensive Care Unit, Hospital Universitari Sagrat Cor, Grupo Quironsalud, Barcelona, Spain
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Rothberg MB, Haessler S, Deshpande A, Yu PC, Lindenauer PK, Zilberberg MD, Higgins TL, Imrey PB. Derivation and validation of a risk assessment model for drug-resistant pathogens in hospitalized patients with community-acquired pneumonia. Infect Control Hosp Epidemiol 2023; 44:1143-1150. [PMID: 36172877 PMCID: PMC10050215 DOI: 10.1017/ice.2022.229] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
OBJECTIVE To derive and validate a model for risk of resistance to first-line community-acquired pneumonia (CAP) therapy. DESIGN We developed a logistic regression prediction model from a large multihospital discharge database and validated it versus the Drug Resistance in Pneumonia (DRIP) score in a holdout sample and another hospital system outside that database. Resistance to first-line CAP therapy (quinolone or third generation cephalosporin plus macrolide) was based on blood or respiratory cultures. SETTING This study was conducted using data from 177 Premier Healthcare database hospitals and 11 Cleveland Clinic hospitals. PARTICIPANTS Adults hospitalized for CAP. EXPOSURE Risk factors for resistant infection. RESULTS Among 138,762 eligible patients in the Premier database, 12,181 (8.8%) had positive cultures and 5,200 (3.8%) had organisms resistant to CAP therapy. Infection with a resistant organism in the previous year was the strongest predictor of resistance; markers of acute illness (eg, receipt of mechanical ventilation or vasopressors) and chronic illness (eg, pressure ulcer, paralysis) were also associated with resistant infections. Our model outperformed the DRIP score with a C-statistic of 0.71 versus 0.63 for the DRIP score (P < .001) in the Premier holdout sample, and 0.65 versus 0.58 (P < .001) in Cleveland Clinic hospitals. Clinicians at Premier facilities used broad-spectrum antibiotics for 20%-30% of patients. In discriminating between patients with and without resistant infections, physician judgment slightly outperformed the DRIP instrument but not our model. CONCLUSIONS Our model predicting infection with a resistant pathogen outperformed both the DRIP score and physician practice in an external validation set. Its integration into practice could reduce unnecessary use of broad-spectrum antibiotics.
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Affiliation(s)
- Michael B. Rothberg
- Center for Value-Based Care Research, Cleveland Clinic Community Care, Cleveland Clinic, Cleveland, Ohio
| | - Sarah Haessler
- Division of Infectious Diseases, University of Massachusetts Medical School – Baystate, Springfield, Massachusetts
| | - Abhishek Deshpande
- Center for Value-Based Care Research, Cleveland Clinic Community Care, Cleveland Clinic, Cleveland, Ohio
- Department of Infectious Disease, Respiratory Institute, Cleveland Clinic, Cleveland, Ohio
| | - Pei-Chun Yu
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio
| | - Peter K. Lindenauer
- Institute for Healthcare Delivery and Population Science and Department of Medicine, University of Massachusetts Medical School–Baystate, Springfield, Massachusetts
| | - Marya D. Zilberberg
- University of Massachusetts, Amherst, Massachusetts, and EviMed Research Group, Goshen, Massachusetts
| | - Thomas L. Higgins
- Division of Pulmonary and Critical Care Medicine, University of Massachusetts Medical School–Baystate, Springfield, Massachusetts
- The Center for Case Management, Natick, Massachusetts
| | - Peter B. Imrey
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio
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Cilloniz C, Torres A. What's Next in Pneumonia? Arch Bronconeumol 2022; 58:208-210. [PMID: 35312596 DOI: 10.1016/j.arbres.2021.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 08/02/2021] [Accepted: 08/02/2021] [Indexed: 12/15/2022]
Affiliation(s)
- Catia Cilloniz
- Department of Pneumology, Hospital Clinic of Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute - IDIBAPS, University of Barcelona, Spain; Biomedical Research Networking Centers in Respiratory Diseases (Ciberes), Barcelona, Spain
| | - Antoni Torres
- Department of Pneumology, Hospital Clinic of Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute - IDIBAPS, University of Barcelona, Spain; Biomedical Research Networking Centers in Respiratory Diseases (Ciberes), Barcelona, Spain.
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Howley F, Keating D, Kelly M, O’Connor R, O’Riordan R. A Service Evaluation of Adherence with Antimicrobial Guidelines in the Treatment of Community-Acquired Pneumonia Before and During the SARS-CoV-2 Outbreak. SN COMPREHENSIVE CLINICAL MEDICINE 2022; 4:225. [PMID: 36258797 PMCID: PMC9559268 DOI: 10.1007/s42399-022-01311-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Accepted: 10/07/2022] [Indexed: 11/05/2022]
Abstract
Antimicrobial stewardship is essential to reducing antimicrobial resistance, reducing costs, and, crucially, ensuring good patient care. Community-acquired pneumonia (CAP) is a common medical condition, the symptoms of which show a significant overlap with those of COVID-19. Following the COVID-19 outbreak in Ireland, patients presenting to our hospital with features of a respiratory infection were more commonly reviewed within 24 hours (24h) of admission by an infectious disease (ID) or respiratory specialist. We aimed to assess how the change in service provision, involving frequent specialist reviews of patients admitted with features of CAP during the first wave of the COVID-19 pandemic, affected antimicrobial stewardship and prescribing practices. Patients admitted under general medical teams treated for CAP from March–April 2020 were included. Retrospective data including demographics, CURB-65 score, and antimicrobial therapy were collected, as well as information on whether the patient had undergone specialist review by an ID or respiratory physician. Data were compared to a similar cohort treated for CAP between November 2019 and January 2020, though in this cohort, before the era of COVID-19, none of the patients had undergone specialist review. Seventy-six patients were included from the March–April 2020 cohort, with 77 from November 2019–January 2020 for comparison. An ID or respiratory specialist reviewed 35 patients from the March–April cohort within 24 h of admission. There was a higher rate of appropriate escalation, de-escalation, and continuation of antibiotics among those reviewed. Less than 20% of patients were started on antibiotics in accordance with CAP guidelines on admission, though the antibiotics initiated were frequently deemed appropriate in the clinical setting. Specialist review increases rates of appropriate antimicrobial prescribing and adherence with hospital guidelines in patients with CAP.
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Affiliation(s)
- Fergal Howley
- grid.416409.e0000 0004 0617 8280Department of General Internal Medicine, St James’s Hospital, Dublin, Ireland
| | - Donal Keating
- grid.416409.e0000 0004 0617 8280Department of General Internal Medicine, St James’s Hospital, Dublin, Ireland
| | - Mary Kelly
- grid.416409.e0000 0004 0617 8280Pharmacy Department, St James’s Hospital, Dublin, Ireland
| | - Roisin O’Connor
- grid.416409.e0000 0004 0617 8280Pharmacy Department, St James’s Hospital, Dublin, Ireland
| | - Ruth O’Riordan
- grid.416409.e0000 0004 0617 8280Department of General Internal Medicine, St James’s Hospital, Dublin, Ireland
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Jeong J, Lee HK. The Role of CD4 + T Cells and Microbiota in the Pathogenesis of Asthma. Int J Mol Sci 2021; 22:11822. [PMID: 34769255 PMCID: PMC8584410 DOI: 10.3390/ijms222111822] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/26/2021] [Accepted: 10/29/2021] [Indexed: 12/22/2022] Open
Abstract
Asthma, a chronic respiratory disease involving variable airflow limitations, exhibits two phenotypes: eosinophilic and neutrophilic. The asthma phenotype must be considered because the prognosis and drug responsiveness of eosinophilic and neutrophilic asthma differ. CD4+ T cells are the main determinant of asthma phenotype. Th2, Th9 and Tfh cells mediate the development of eosinophilic asthma, whereas Th1 and Th17 cells mediate the development of neutrophilic asthma. Elucidating the biological roles of CD4+ T cells is thus essential for developing effective asthma treatments and predicting a patient's prognosis. Commensal bacteria also play a key role in the pathogenesis of asthma. Beneficial bacteria within the host act to suppress asthma, whereas harmful bacteria exacerbate asthma. Recent literature indicates that imbalances between beneficial and harmful bacteria affect the differentiation of CD4+ T cells, leading to the development of asthma. Correcting bacterial imbalances using probiotics reportedly improves asthma symptoms. In this review, we investigate the effects of crosstalk between the microbiota and CD4+ T cells on the development of asthma.
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Affiliation(s)
| | - Heung Kyu Lee
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea;
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Tiseo G, Arena F, Borrè S, Campanile F, Falcone M, Mussini C, Pea F, Sganga G, Stefani S, Venditti M. Diagnostic stewardship based on patient profiles: differential approaches in acute versus chronic infectious syndromes. Expert Rev Anti Infect Ther 2021; 19:1373-1383. [PMID: 33970746 DOI: 10.1080/14787210.2021.1926986] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Introduction: New diagnostics may be useful in clinical practice, especially in contexts of high prevalence of multidrug-resistant organisms (MDRO). However, misuse of diagnostic tools may lead to increased costs and worse patient outcome. Conventional and new techniques should be appropriately positioned in diagnostic algorithms to guide an appropriate use of antimicrobial therapy.Areas covered: A panel of experts identified 4 main areas in which the implementation of diagnostic stewardship is needed. Among chronic infections, bone and prosthetic joint infections and subacute-chronic intravascular infections and endocarditis represent common challenges for clinicians. Among acute infections, bloodstream infections and community-acquired pneumonia may be associated with high mortality and require appropriate diagnostic approach.Expert opinion: Diagnostic stewardship aims to improve the appropriate use of microbiological diagnostics to guide therapeutic decisions through appropriate and timely diagnostic testing. Here, diagnostic algorithms based on different patient profiles are proposed for chronic and acute clinical syndromes. In each clinical scenario, combining conventional and new diagnostic techniques is crucial to make a rapid and accurate diagnosis and to guide the selection of antimicrobial therapy. Barriers related to the implementation of new rapid diagnostic tools, such as high initial costs, may be overcome through their rational and structured use.
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Affiliation(s)
- Giusy Tiseo
- Infectious Disease Unit, Azienda Ospedaliera Universitaria Pisana, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Fabio Arena
- Infectious Disease Unit, Azienda Ospedaliera Universitaria Pisana, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.,IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy
| | - Silvio Borrè
- Infectious Diseases Unit, Sant'Andrea Hospital Vercelli, Vercelli, Italy
| | - Floriana Campanile
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Marco Falcone
- Infectious Disease Unit, Azienda Ospedaliera Universitaria Pisana, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Cristina Mussini
- Department of Infectious Diseases, Azienda Ospedaliero-Universitaria, Policlinico of Modena, Modena, Italy
| | - Federico Pea
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.,SSD Clinical Pharmacology, University Hospital IRCCS Policlinico Sant'Orsola, Bologna, Italy
| | - Gabriele Sganga
- Emergency Surgery, Fondazione Policlinico Agostino Gemelli IRCCS of Rome, Rome, Italy
| | - Stefania Stefani
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Mario Venditti
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
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