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2. Management of intra-abdominal infections: recommendations by the Italian council for the optimization of antimicrobial use

Author

Sartelli, Massimo, Tascini, Carlo, Coccolini, Federico, Dellai, Fabiana, Ansaloni, Luca, Antonelli, Massimo, Bartoletti, Michele, Bassetti, Matteo, Boncagni, Federico, Carlini, Massimo, Cattelan, Anna Maria, Cavaliere, Arturo, Ceresoli, Marco, Cipriano, Alessandro, Cortegiani, Andrea, Cortese, Francesco, Cristini, Francesco, Cucinotta, Eugenio, Dalfino, Lidia, De Pascale, Gennaro, De Rosa, Francesco Giuseppe, Falcone, Marco, Forfori, Francesco, Fugazzola, Paola, Gatti, Milo, Gentile, Ivan, Ghiadoni, Lorenzo, Giannella, Maddalena, Giarratano, Antonino, Giordano, Alessio, Girardis, Massimo, Mastroianni, Claudio, Monti, Gianpaola, Montori, Giulia, Palmieri, Miriam, Pani, Marcello, Paolillo, Ciro, Parini, Dario, Parruti, Giustino, Pasero, Daniela, Pea, Federico, Peghin, Maddalena, Petrosillo, Nicola, Podda, Mauro, Rizzo, Caterina, Rossolini, Gian Maria, Russo, Alessandro, Scoccia, Loredana, Sganga, Gabriele, Signorini, Liana, Stefani, Stefania, Tumbarello, Mario, Tumietto, Fabio, Valentino, Massimo, Venditti, Mario, Viaggi, Bruno, Vivaldi, Francesca, Zaghi, Claudia, Labricciosa, Francesco M., Abu-Zidan, Fikri, Catena, Fausto, and Viale, Pierluigi

Published
2024
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3. Treatment of critically ill patients with cefiderocol for infections caused by multidrug-resistant pathogens: review of the evidence.

Author

Viale, Pierluigi, Sandrock, Christian E, Ramirez, Paula, Rossolini, Gian Maria, and Lodise, Thomas P

Subjects
Appropriate antibiotic, Cefiderocol, Critically ill, Dosing, Multidrug-resistant Gram-negative bacteria, Nosocomial pneumonia, Sepsis, Pneumonia & Influenza, Clinical Research, Clinical Trials and Supportive Activities, Patient Safety, Emerging Infectious Diseases, Pneumonia, Hematology, Lung, Antimicrobial Resistance, Infectious Diseases, Prevention, 2.2 Factors relating to the physical environment, 5.1 Pharmaceuticals, Aetiology, Evaluation of treatments and therapeutic interventions, Development of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Clinical Sciences, Public Health and Health Services
Abstract

Appropriate antibiotic treatment for critically ill patients with serious Gram-negative infections in the intensive care unit is crucial to minimize morbidity and mortality. Several new antibiotics have shown in vitro activity against carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat resistant Pseudomonas aeruginosa. Cefiderocol is the first approved siderophore beta-lactam antibiotic with potent activity against multidrug-resistant, carbapenem-resistant, difficult-to-treat or extensively drug-resistant Gram-negative pathogens, which have limited treatment options. The spectrum of activity of cefiderocol includes drug-resistant strains of Acinetobacter baumannii, P. aeruginosa, Stenotrophomonas maltophilia, Achromobacter spp. and Burkholderia spp. and CRE that produce serine- and/or metallo-carbapenemases. Phase 1 studies established that cefiderocol achieves adequate concentration in the epithelial lining fluid in the lung and requires dosing adjustment for renal function, including patients with augmented renal clearance and continuous renal-replacement therapy (CRRT); no clinically significant drug-drug interactions are expected. The non-inferiority of cefiderocol versus high-dose, extended-infusion meropenem in all-cause mortality (ACM) rates at day 14 was demonstrated in the randomized, double-blind APEKS-NP Phase 3 clinical study in patients with nosocomial pneumonia caused by suspected or confirmed Gram-negative bacteria. Furthermore, the efficacy of cefiderocol was investigated in the randomized, open-label, pathogen-focused, descriptive CREDIBLE-CR Phase 3 clinical study in its target patient population with serious carbapenem-resistant Gram-negative infections, including hospitalized patients with nosocomial pneumonia, bloodstream infection/sepsis, or complicated urinary tract infections. However, a numerically greater ACM rate with cefiderocol compared with BAT led to the inclusion of a warning in US and European prescribing information. Cefiderocol susceptibility results obtained with commercial tests should be carefully evaluated due to current issues regarding their accuracy and reliability. Since its approval, real-world evidence in patients with multidrug-resistant and carbapenem-resistant Gram-negative bacterial infections suggests that cefiderocol can be efficacious in certain critically ill patient groups, such as those requiring mechanical ventilation for COVID-19 pneumonia with subsequently acquired Gram-negative bacterial superinfection, and patients with CRRT and/or extracorporeal membrane oxygenation. In this article, we review the microbiological spectrum, pharmacokinetics/pharmacodynamics, efficacy and safety profiles and real-world evidence for cefiderocol, and look at future considerations for its role in the treatment of critically ill patients with challenging Gram-negative bacterial infections.

Published
2023

8. Effect of antimetabolite regimen on cellular and humoral immune response to SARS-COV-2 vaccination in solid organ transplant recipients

Author

Capone, Manuela, Vanni, Anna, Salvati, Lorenzo, Lamacchia, Giulia, Mazzoni, Alessio, Maggi, Laura, Cosmi, Lorenzo, Liotta, Francesco, Romagnani, Paola, Cirillo, Luigi, Buti, Elisa, Terlizzi, Vito, Azzari, Chiara, Citera, Francesco, Barbati, Federica, Rossolini, Gian Maria, Bresci, Silvia, Borchi, Beatrice, Cavallo, Annalisa, Mencarini, Jessica, Francalanci, Emanuela, Kiros, Seble Tekle, Bartoloni, Alessandro, and Annunziato, Francesco

Published
2024
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11. Doubts and concerns about COVID-19 uncertainties on imaging data, clinical score, and outcomes

Author

Nardi, Cosimo, Magnini, Andrea, Calistri, Linda, Cavigli, Edoardo, Peired, Anna Julie, Rastrelli, Vieri, Carlesi, Edoardo, Zantonelli, Giulia, Smorchkova, Olga, Cinci, Lorenzo, Orlandi, Martina, Landini, Nicholas, Berillo, Edoardo, Lorini, Chiara, Mencarini, Jessica, Colao, Maria Grazia, Gori, Leonardo, Luzzi, Valentina, Lazzeri, Chiara, Cipriani, Elisa, Bonizzoli, Manuela, Pieralli, Filippo, Nozzoli, Carlo, Morettini, Alessandro, Lavorini, Federico, Bartoloni, Alessandro, Rossolini, Gian Maria, Matucci-Cerinic, Marco, Tomassetti, Sara, and Colagrande, Stefano

Published
2023
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12. The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis

Author

Walker, Timothy M, Miotto, Paolo, Köser, Claudio U, Fowler, Philip W, Knaggs, Jeff, Iqbal, Zamin, Hunt, Martin, Chindelevitch, Leonid, Farhat, Maha R, Cirillo, Daniela Maria, Comas, Iñaki, Posey, James, Omar, Shaheed V, Peto, Timothy EA, Suresh, Anita, Uplekar, Swapna, Laurent, Sacha, Colman, Rebecca E, Nathanson, Carl-Michael, Zignol, Matteo, Walker, Ann Sarah, Crook, Derrick W, Ismail, Nazir, Rodwell, Timothy C, Consortium, the SeqTreat Consortium CRyPTIC, Walker, A Sarah, Steyn, Adrie JC, Lalvani, Ajit, Baulard, Alain, Christoffels, Alan, Mendoza-Ticona, Alberto, Trovato, Alberto, Skrahina, Alena, Lachapelle, Alexander S, Brankin, Alice, Piatek, Amy, Cruz, Ana Gibertoni, Koch, Anastasia, Cabibbe, Andrea Maurizio, Spitaleri, Andrea, Brandao, Angela P, Chaiprasert, Angkana, Barbova, Anna, Van Rie, Annelies, Ghodousi, Arash, Bainomugisa, Arnold, Mandal, Ayan, Roohi, Aysha, Javid, Babak, Zhu, Baoli, Letcher, Brice, Rodrigues, Camilla, Nimmo, Camus, NATHANSON, Carl-Michael, Duncan, Carla, Coulter, Christopher, Utpatel, Christian, Liu, Chunfa, Grazian, Clara, Kong, Clare, Wilson, Daniel J, Matias, Daniela, Jorgensen, Danielle, Zimenkov, Danila, Chetty, Darren, Moore, David AJ, Clifton, David A, van Soolingen, Dick, Liu, Dongxin, Kohlerschmidt, Donna, Barreira, Draurio, Ngcamu, Dumisani, Lazaro, Elias David Santos, Kelly, Ellis, Borroni, Emanuele, Roycroft, Emma, Andre, Emmanuel, Böttger, Erik C, Robinson, Esther, Menardo, Fabrizio, Mendes, Flavia F, Jamieson, Frances B, Coll, Francesc, Gao, George Fu, Kasule, George W, Rossolini, Gian Maria, Rodger, Gillian, Smith, E Grace, Meintjes, Graeme, Thwaites, Guy, Hoffmann, Harald, Albert, Heidi, Cox, Helen, Laurenson, Ian F, and Arandjelovic, Irena

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Microbiology, Clinical Sciences, Tuberculosis, Infectious Diseases, Rare Diseases, Antimicrobial Resistance, Orphan Drug, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Infection, Good Health and Well Being, Antitubercular Agents, Drug Resistance, Ethambutol, Microbial Sensitivity Tests, Mutation, Mycobacterium tuberculosis, World Health Organization, CRyPTIC Consortium, Seq&Treat Consortium, Immunology, Medical microbiology
Abstract

BackgroundMolecular diagnostics are considered the most promising route to achieving rapid, universal drug susceptibility testing for Mycobacterium tuberculosiscomplex (MTBC). We aimed to generate a WHO endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction.MethodsA candidate gene approach was used to identify mutations as associated with resistance, or consistent with susceptibility, for 13 WHO endorsed anti-tuberculosis drugs. 38,215 MTBC isolates with paired whole-genome sequencing and phenotypic drug susceptibility testing data were amassed from 45 countries. For each mutation, a contingency table of binary phenotypes and presence or absence of the mutation computed positive predictive value, and Fisher's exact tests generated odds ratios and Benjamini-Hochberg corrected p-values. Mutations were graded as Associated with Resistance if present in at least 5 isolates, if the odds ratio was >1 with a statistically significant corrected p-value, and if the lower bound of the 95% confidence interval on the positive predictive value for phenotypic resistance was >25%. A series of expert rules were applied for final confidence grading of each mutation.Findings15,667 associations were computed for 13,211 unique mutations linked to one or more drugs. 1,149/15,667 (7·3%) mutations were classified as associated with phenotypic resistance and 107/15,667 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was >80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were classified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs.InterpretationThis first WHO endorsed catalogue of molecular targets for MTBC drug susceptibility testing provides a global standard for resistance interpretation. Its existence should encourage the implementation of molecular diagnostics by National Tuberculosis Programmes.FundingUNITAID, Wellcome, MRC, BMGF.

Published
2022

14. Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA)

Author

Serna, Almudena de la, Monteau, Sophie, Palomo, Virginia, Soriano, Elena, Gutierrez, David, Moreno, Elisa, Sojo-Dorado, Jesus, Morales, Isabel, Maldonado, Natalia, Santis, Lucia Valiente de, Ciezar, Antonio Plata, Ruiz Mesa, Juan Diego, Diaz, Beatriz Sobrino, Gomez, Ignacio Marquez, Camacho, Ines Perez, Cano, Angela, Frutos-Adame, Azahara, Guzman-Puche, Julia, Gracia-Ahufinger, Irene, Perez-Nadales, Elena, Torre-Gimenez, Julian, Pyrpasopoulou, Athina, Iosifidis, Elias, Chorafa, Elsa, Radovanovic, Ivana, Petrovic, Sladjana, Cvetkovi, Slavica, Melentijevic, Srdjan-Sanja, Bicmen, Can, Senol, Gunes, Tubau, Fe, Camara, Jordi, Daniel Gumucio, Victor, Bassoulis, Dimitris, Deliolanis, John, Pitiriga, Vassiliki Ch., Triarides, Nikolaos, Argiti, Efstathia, Legakis, Nikolaos J., Margarita, Kyriakidou, Gijón-Cordero, Desirée, Ruiz-Garbajosa, Patricia, Rossolini, Gian Maria, Nica, Maria, Talapan, Daniela, Medić, Deana, Prijić, Sanja Maričić, Caballero, Mireia Cantero, Ramírez, Lina M Parra, Bilgin, Hüseyin, Dalekos, George N., Stefos, Aggelos, Spyridis, Nikolaos, Michos, Athanasios, De Rosa, Francesco Giuseppe, Cavallo, Rossana, Petrosillo, Nicola, Dicaro, Antonio, Landini, Maria Paola, degli Atti, Marta Luisa Ciofi, Masanovic, Mileva, Matkovic, Dusan, Tsiodras, Sotirios, Blasi, Francesco, pasquale, Marta Di, Viscoli, Claudio, Vata, Andrei, Dorneanu, Olivia, Kapisyzi, Perlat, Vince, Adriana, Tsigou, Evdoxia, Maltezos, Efstratios, Komnos, Apostolos, Gogos, Charalampos, Franzetti, Fabio, Antonelli, Massimo, Lupse, Mihaela, Corneci, Dan, Tomescu, Dana, Georgescu, Anca, Bukarica, Ljiljana, Mitrović, Goran, Krstić, Nataša Lukić, Kurti, Arsim, Reuter, Sandra, Díaz-Pollán, Beatriz, Sabater, Julia Origüen, Muñoz, Patricia, Azap, Alpay, ancak, Banu, Sahin, Arife, Akalin, Halis, Paniagua-García, María, Bravo-Ferrer, Jose M., Pérez-Galera, Salvador, Kostyanev, Tomislav, de Kraker, Marlieke E.A., Feifel, Jan, Palacios-Baena, Zaira R., Schotsman, Joost, Cantón, Rafael, Daikos, George L., Carevic, Biljana, Dragovac, Gorana, Tan, Lionel K., Raka, Lul, Hristea, Adriana, Viale, Pierluigi, Akova, Murat, Cano, Ángela, Reguera, Jose María, Bartoloni, Alessandro, Florescu, Simin-Aysel, Benea, Serban, Asensio, Ángel, Korten, Volkan, Grundmann, Hajo, Goossens, Herman, Bonten, Marc J., Gutiérrez-Gutiérrez, Belén, and Rodríguez-Baño, Jesús

Published
2024
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16. Wastewater surveillance of SARS-CoV-2 variants in October–November 2022 in Italy: detection of XBB.1, BA.2.75 and rapid spread of the BQ.1 lineage

Author

Palma, Achille, Calabria, Adelaide, Carnevali, Agnese, Nehludoff, Albano, Stenico, Alberta, Izzotti, Alberto, Barca, Alessandra, Tosco, Alessandra, Porta, Amalia, Lombardi, Annalisa, Voli, Antonia, Franzetti, Andrea, Ciccaglione, Angela, Costa, Angela, D’Argenzio, Angelo, Romano, Angelo, Pariani, Anna, Carducci, Annalaura, Grucci, Annalisa, Prast, Anna-Maria, Agodi, Antonella, Cersini, Antonella, Giorgi, Antonella, Bertasi, Barbara, Griglio, Bartolomeo, Ancona, Carla, Maida, Carmelo Massimo, Montanaro, Carmen, Filizzolo, Chiara, Ottaviano, Claudio, Cocuzza, Clementina, Pignata, Cristina, Nasci, Daniele, Cereda, Danilo, Oliva, Desdemona, Giorgi, Doriana Antonella, Malacaria, Edoardo, Grasselli, Elena, Nicosia, Elena, Carraro, Elisabetta, Ammoni, Emanuela, Grange, Eric, Federici, Ermanno, Filippetti, Fabio, Tramuto, Fabio, Guarneri, Flavia, Serio, Flavia, Damasco, Florida, Palumbo, Franca, Apollonio, Francesca, Cutrupi, Francesca, Gucciardi, Francesca, Pennino, Francesca, Russo, Francesca, Triggiano, Francesco, Rigoli, Franco, Pietrella, Gabriele, Trani, Gabriella, Rossolini, Gian Maria, Bulotta, Giorgia, Fusco, Giovanna, La Vecchia, Giovanna, Alborali, Giovanni, Giammanco, Giovanni, Santoro, Giovanni, Pitter, Gisella, Purpari, Giuseppa, Aprea, Giuseppe, Di Vittorio, Giuseppe, Folino, Giuseppe, Lauria, Giuseppe, Federigi, Ileana, Amoruso, Irene, Ferrante, Irene, Tomesani, Irene, De Lellis, Laura, Pellegrinelli, Laura, Demetz, Lea, Gentili, Lisa, Richiardi, Lisa, Zago, Lorella, Masieri, Lorena, Decastelli, Lucia, Bolognini, Luigi, Cossentino, Luigi, Bianchi, Manila, Verani, Marco, Zampini, Marco, Ferrante, Margherita, Cadonna, Maria, Montagna, Maria Teresa, Scicluna, Maria Teresa, Arizzi, Mariaconcetta, Mariuz, Marika, Palermo, Mario, Bellisomi, Marta, Paniccià, Marta, Barchitta, Martina, Ramazzotti, Matteo, Postinghel, Mattia, Viscardi, Maurizio, Ruffier, Mauro, Petricciuolo, Maya, La Bianca, Michele, Colitti, Michele, Monfrinotti, Monica, Fontani, Nadia, Formenti, Nicoletta, Mongelli, Onofrio, De Giglio, Osvalda, Angelini, Paola, Foladori, Paola, Torlontano, Paolo, Calà, Piergiuseppe, Cifarelli, Rosa Anna, Binda, Sandro, Briscolini, Sara, Castiglioni, Sara, Bonetta, Silvia, Magi, Silvia, Scattolini, Silvia, Schiarea, Silvia, De Grazia, Simona, Rosatto, Stefano, Baldovin, Tatjana, Primache, Valeria, Groppi, Vanessa, Acciari, Vicdalia Aniela, Mazzucco, Walter, La Rosa, G., Brandtner, D., Bonanno Ferraro, G., Veneri, C., Mancini, P., Iaconelli, M., Lucentini, L., Del Giudice, C., Orlandi, L., and Suffredini, E.

Published
2023
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17. Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)

Author

de la Serna, Almudena, Monteau, Sophie, Palomo, Virginia, Soriano, Elena, Gutierrez, David, Moreno, Elisa, Palacios, Zaira, Morales, Isabel, Maldonado, Natalia, Ciezar, Antonio Plata, Ruiz Mesa, Juan Diego, Diaz, Beatriz Sobrino, Gomez, Ignacio Marquez, Camacho, Ines Perez, Frutos-Adame, Azahara, Guzman-Puche, Julia, Gracia-Ahufinger, Irene, Perez-Nadales, Elena, Torre-Gimenez, Julian, Pyrpasopoulou, Athina, Iosifidis, Elias, Chorafa, Elsa, Radovanovic, Ivana, Petrovic, Sladjana, Cvetkovi, Slavica, Melentijevic, Srdjan-Sanja, Bicmen, Can, Senol, Gunes, Tubau, Fe, Camara, Jordi, Gumucio, Victor Daniel, Bassoulis, Dimitris, Deliolanis, John, Pitiriga, Vassiliki Ch., Triarides, Nikolaos, Argiti, Efstathia, Legakis, Nikolaos J., Margarita, Kyriakidou, Gijón-Cordero, Desirée, Ruiz-Garbajosa, Patricia, Bartoloni, Alessandro, Rossolini, Gian Maria, Florescu, Simin-Aysel, Nica, Maria, Benea, Serban, Talapan, Daniela, Medić, Deana, Prijić, Sanja Maričić, Caballero, Mireia Cantero, Parra Ramírez, Lina M., Korten, Volkan, Bilgin, Hüseyin, Dalekos, George N., Stefos, Aggelos, Spyridis, Nikolaos, Michos, Athanasios, De Rosa, Francesco Giuseppe, Cavallo, Rossana, Petrosillo, Nicola, Dicaro, Antonio, Landini, Maria Paola, Ciofi degli Atti, Marta Luisa, Masanovic, Mileva, Matkovic, Dusan, Tsiodras, Sotirios, Blasi, Francesco, Di pasquale, Marta, Viscoli, Claudio, Vata, Andrei, Dorneanu, Olivia, Kapisyzi, Perlat, Vince, Adriana, Tsigou, Evdoxia, Maltezos, Efstratios, Komnos, Apostolos, Gogos, Charalampos, Franzetti, Fabio, Antonelli, Massimo, Lupse, Mihaela, Corneci, Dan, Tomescu, Dana, Georgescu, Anca, Bukarica, Ljiljana, Mitrović, Goran, Krstić, Nataša Lukić, Kurti, Arsim, Díaz-Pollán, Beatriz, Sabater, Julia Origüen, Muñoz, Patricia, Azap, Alpay, Sancak, Banu, Sahin, Arife, Akalin, Halis, Pérez-Galera, Salvador, Bravo-Ferrer, Jose M., Paniagua, María, Kostyanev, Tomislav, de Kraker, Marlieke E.A., Feifel, Jan, Sojo-Dorado, Jesús, Schotsman, Joost, Cantón, Rafael, Daikos, George L., Carevic, Biljana, Dragovac, Gorana, Tan, Lionel K., Raka, Lul, Hristea, Adriana, Viale, Pierluigi, Akova, Murat, Reguera, Jose María, Valiente de Santis, Lucía, Torre-Cisneros, Julián, Cano, Ángela, Roilides, Emmanuel, Radulovic, Lili, Kirakli, Cenk, Shaw, Evelyn, Falagas, Matthew E., Pintado, Vicente, Goossens, Herman, Bonten, Marc J., Gutiérrez-Gutiérrez, Belén, and Rodriguez-Baño, Jesús

Published
2023
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18. Clinical and Immunological Features of SARS-CoV-2 Breakthrough Infections in Vaccinated Individuals Requiring Hospitalization

Author

Lamacchia, Giulia, Mazzoni, Alessio, Spinicci, Michele, Vanni, Anna, Salvati, Lorenzo, Peruzzi, Benedetta, Bencini, Sara, Capone, Manuela, Carnasciali, Alberto, Farahvachi, Parham, Rocca, Arianna, Kiros, Seble Tekle, Graziani, Lucia, Zammarchi, Lorenzo, Mencarini, Jessica, Colao, Maria Grazia, Caporale, Roberto, Liotta, Francesco, Cosmi, Lorenzo, Rossolini, Gian Maria, Bartoloni, Alessandro, Maggi, Laura, and Annunziato, Francesco

Published
2022
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19. Long-term SARS-CoV-2 Asymptomatic Carriage in an Immunocompromised Host: Clinical, Immunological, and Virological Implications

Author

Spinicci, Michele, Mazzoni, Alessio, Coppi, Marco, Antonelli, Alberto, Salvati, Lorenzo, Maggi, Laura, Basile, Gregorio, Graziani, Lucia, Di Lauria, Nicoletta, Di Pilato, Vincenzo, Kiros, Seble Tekle, Beccastrini, Enrico, Saccardi, Riccardo, Angileri, Manuela, Cecchi, Michele, Cusi, Maria Grazia, Rossolini, Gian Maria, Annunziato, Francesco, Bartoloni, Alessandro, and Parronchi, Paola

Published
2022
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24. Characterization of four novel bacteriophages targeting multi-drug resistant Klebsiella pneumoniae strains of sequence type 147 and 307.

Author

Ponsecchi, Greta, Olimpieri, Tommaso, Poerio, Noemi, Antonelli, Alberto, Coppi, Marco, Di Lallo, Gustavo, Gentile, Mariangela, Paccagnini, Eugenio, Lupetti, Pietro, Lubello, Claudio, Rossolini, Gian Maria, Fraziano, Maurizio, and D'Andrea, Marco Maria

Subjects
CARBAPENEM-resistant bacteria, MULTIDRUG resistance, PATHOGENIC bacteria, DRUG resistance in bacteria, BACTERIAL diseases, KLEBSIELLA pneumoniae, BACTERIOPHAGES
Abstract

The global dissemination of multi-drug resistant (MDR) pathogenic bacteria requires the rapid research and development of alternative therapies that can support or replace conventional antibiotics. Among MDR pathogens, carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are of particular concern due to their extensive resistance profiles, global dissemination in hospital environments, and their major role in some life-threatening infections. Phages, or some of their components, are recognized as one of the potential alternatives that might be helpful to treat bacterial infections. In this study, we have isolated and characterized four lytic bacteriophages targeting K. pneumoniae strains of Sequence Type (ST) 307 or ST147, two predominant high-risk clones of CR-Kp. Phages, designated vB_KpS_GP-1, vB_KpP_GP-2, vB_KpP_GP-4, and vB_KpP_GP-5, were isolated from sewage wastewater samples. The vB_KpS_GP-1 phage was a siphovirus unable to establish lysogeny with its host, while the other three were podoviruses. While 85.7% of K. pneumoniae strains of ST307 were selectively lysed by the phages vB_KpS_GP-1 or vB_KpP_GP-5, the other two phages were able to lyse all the tested strains of ST147 (n = 12). Phages were stable over a broad pH and temperature range and were characterized by burst sizes of 10-100 plaque forming units and latency periods of 10-50 minutes. Genome sequencing confirmed the absence of antibiotic resistance genes, virulence factors or toxins and revealed that two phages were likely members of new genera. Given their strictly lytic nature and high selectivity towards two of the major high-risk clones of K. pneumoniae, cocktails of these phages could represent promising candidates for further evaluation in in vivo experimental models of K. pneumoniae infection. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Evaluation of three commercial lateral flow immunoassays for the detection of KPC, VIM, NDM, IMP and OXA-48-like carbapenemases.

Author

Cuffari, Sara, Aiezza, Noemi, Antonelli, Alberto, Giani, Tommaso, and Rossolini, Gian Maria

Subjects
INFECTION prevention, FLUID flow, MEDICAL technology, ANTI-infective agents, GRAM-negative bacteria, ENTEROBACTERIACEAE
Abstract

The article evaluates three commercial lateral flow immunoassays for detecting carbapenemases in Gram-negative bacteria, emphasizing the importance of accurate identification for infection control and treatment. Results showed varying detection capabilities for different carbapenemase families, underscoring the need for timely identification. The document provides a detailed overview of various strains of bacteria, their species, and the carbapenemases they possess, essential for understanding resistance patterns and aiding in research and treatment strategies. The study found that while all three systems exhibited 100% specificity, some variants were missed, indicating challenges in diagnostic sensitivity and the need for further testing to enhance performance. [Extracted from the article]

Published
2024
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27. Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinology

Author

Cuscino, Nicola, Fatima, Ayesha, Di Pilato, Vincenzo, Bulati, Matteo, Alfano, Caterina, Monaca, Elisa, Di Mento, Giuseppina, Di Carlo, Daniele, Cardinale, Francesca, Monaco, Francesco, Rossolini, Gian Maria, Khan, Asif M., Conaldi, Pier Giulio, and Douradinha, Bruno

Published
2022
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28. Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing

Author

Allix-Béguec, Caroline, Arandjelovic, Irena, Bi, Lijun, Beckert, Patrick, Bonnet, Maryline, Bradley, Phelim, Cabibbe, Andrea M, Cancino-Muñoz, Irving, Caulfield, Mark J, Chaiprasert, Angkana, Cirillo, Daniela, Clifton, David, Comas, Iñaki, Crook, Derrick W, De Filippo, Maria Rosaria, de Neeling, Han, Diel, Roland, Drobniewski, Francis A, Faksri, Kiatichai, Farhat, Maha R, Fleming, Joy, Fowler, Philip, Fowler, Tom A, Gao, Qian, Gardy, Jennifer, Gascoyne-Binzi, Deborah, Cruz, Ana Gibertoni, Gil-Brusola, Ana, Golubchik, Tanya, Gonzalo, Ximena, Grandjean, Louis, He, Guangxue, Guthrie, Jennifer L, Hoosdally, Sarah, Hunt, Martin, Iqbal, Zamin, Ismail, Nazir, Johnston, James, Khanzada, Faisal Masood, Khor, Chiea Chuen, Kohl, Thomas A, Kong, Clare, Lipworth, Sam, Liu, Qingyun, Maphalala, Gugu, Martinez, Elena, Mathys, Vanessa, Merker, Matthias, Miotto, Paolo, Mistry, Nerges, Moore, David, Murray, Megan, Niemann, Stefan, Ong, Rick Twee-Hee, Peto, Tim EA, Posey, James E, Prammananan, Therdsak, Pym, Alexander, Rodrigues, Camilla, Rodrigues, Mabel, Rodwell, Timothy, Rossolini, Gian Maria, Padilla, Elisabeth Sánchez, Schito, Marco, Shen, Xin, Shendure, Jay, Sintchenko, Vitali, Sloutsky, Alex, Smith, E Grace, Snyder, Matthew, Soetaert, Karine, Starks, Angela M, Supply, Philip, Suriyapol, Prapat, Tahseen, Sabira, Tang, Patrick, Teo, Yik-Ying, Thuong, Thuong Nguyen Thuy, Thwaites, Guy, Tortoli, Enrico, Omar, Shaheed Vally, van Soolingen, Dick, Walker, A Sarah, Walker, Timothy M, Wilcox, Mark, Wilson, Daniel J, Wyllie, David, Yang, Yang, Zhang, Hongtai, Zhao, Yanlin, and Zhu, Baoli

Subjects
Genetics, Human Genome, Tuberculosis, Clinical Research, Patient Safety, Prevention, Rare Diseases, Infectious Diseases, Antimicrobial Resistance, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Infection, Good Health and Well Being, Antitubercular Agents, Drug Resistance, Bacterial, Ethambutol, Genome, Bacterial, Genotype, Humans, Isoniazid, Microbial Sensitivity Tests, Mutation, Mycobacterium tuberculosis, Phenotype, Pyrazinamide, Rifampin, Whole Genome Sequencing, CRyPTIC Consortium and the 100, 000 Genomes Project, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundThe World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear.MethodsWe obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance.ResultsA total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted.ConclusionsGenotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.).

Published
2018

39. Use of the FebriDx point-of-care test for the exclusion of SARS-CoV-2 diagnosis in a population with acute respiratory infection during the second (COVID-19) wave in Italy

Author

Lagi, Filippo, Trevisan, Sasha, Piccica, Matteo, Graziani, Lucia, Basile, Gregorio, Mencarini, Jessica, Borchi, Beatrice, Menicacci, Lorenzo, Vaudo, Micol, Scotti, Valentina, Fabbri, Alessia, Bandini, Giulia, Tozzetti, Camilla, Berni, Andrea, Aiezza, Noemi, Pestelli, Giulia, Turchi, Valerio, Pignone, Alberto Moggi, Poggesi, Loredana, Nozzoli, Carlo, Morettini, Alessandro, Rossolini, Gian Maria, and Bartoloni, Alessandro

Published
2021
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40. Antimicrobial resistance research in a post-pandemic world: Insights on antimicrobial resistance research in the COVID-19 pandemic

Author

Rodríguez-Baño, Jesús, Rossolini, Gian Maria, Schultsz, Constance, Tacconelli, Evelina, Murthy, Srinivas, Ohmagari, Norio, Holmes, Alison, Bachmann, Till, Goossens, Herman, Canton, Rafael, Roberts, Adam P., Henriques-Normark, Birgitta, Clancy, Cornelius J., Huttner, Benedikt, Fagerstedt, Patriq, Lahiri, Shawon, Kaushic, Charu, Hoffman, Steven J., Warren, Margo, Zoubiane, Ghada, Essack, Sabiha, Laxminarayan, Ramanan, and Plant, Laura

Published
2021
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41. Amelioration of Serum Aβ Levels and Cognitive Impairment in APPPS1 Transgenic Mice Following Symbiotic Administration.

Author

Traini, Chiara, Bulli, Irene, Sarti, Giorgia, Morecchiato, Fabio, Coppi, Marco, Rossolini, Gian Maria, Di Pilato, Vincenzo, and Vannucchi, Maria Giuliana

Abstract

Alzheimer's disease (AD) is a neurodegenerative process responsible for almost 70% of all cases of dementia. The clinical signs consist in progressive and irreversible loss of memory, cognitive, and behavioral functions. The main histopathological hallmark is the accumulation of amyloid-ß (Aß) peptide fibrils in the brain. To date, the origin of Aß has not been determined. Recent studies have shown that the gut microbiota produces Aß, and dysbiotic states have been identified in AD patients and animal models of AD. Starting from the hypothesis that maintaining or restoring the microbiota's eubiosis is essential to control Aß's production and deposition in the brain, we used a mixture of probiotics and prebiotics (symbiotic) to treat APPPS1 male and female mice, an animal model of AD, from 2 to 8 months of age and evaluated their cognitive performances, mucus secretion, Aβ serum concentration, and microbiota composition. The results showed that the treatment was able to prevent the memory deficits, the reduced mucus secretion, the increased Aβ blood levels, and the imbalance in the gut microbiota found in APPPS1 mice. The present study demonstrates that the gut–brain axis plays a critical role in the genesis of cognitive impairment, and that modulation of the gut microbiota can ameliorate AD's symptomatology. [ABSTRACT FROM AUTHOR]

Published
2024
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42. Verifying the feasibility of wastewater-based epidemiological monitoring for the small catchment and sewage networks with significant pretreatment.

Author

Sartirano, Daniele, Morecchiato, Fabio, Antonelli, Alberto, Lotti, Tommaso, Morelli, Damasco, Ramazzotti, Matteo, Rossolini, Gian Maria, and Lubello, Claudio

Subjects
SARS-CoV-2, COVID-19, PUBLIC health, WASTEWATER treatment, SEWAGE disposal plants, SEPTIC tanks
Abstract

Wastewater-based epidemiology (WBE) has emerged as a valuable tool for COVID-19 monitoring, especially as the frequency of clinical testing diminishes. Beyond COronaVIrus Disease 19 (COVID-19), the tool's versatility extends to addressing various public health concerns, including antibiotic resistance and drug consumption. However, the complexity of sewage systems introduces noise when measuring chemical tracer concentrations, potentially compromising their applicability for modeling. In our study, we detail the approach adopted to determine the concentration of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) ribonucleiec acid (RNA) in wastewater from the Ponte a Niccheri wastewater treatment plant in Tuscany (Italy), with a sample size of N = 13,935 inhabitants. The unique characteristics of this wastewater system, including mandatory pretreatment in septic tanks with extended retention times, the presence of a hospital for COVID-19 patients, and mixed sewage networks, posed additional challenges. Nevertheless, our results highlight a robust and significant correlation between our measurements and the number of infections within the wastewater treatment plant’s catchment area at the time of sampling. A simple linear model also shows promising results in estimating the number of infected people within the area. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Potential value of a rapid syndromic multiplex PCR for the diagnosis of native and prosthetic joint infections: a real-world evidence study

Author

Pascual, Stéphanie, primary, Noble, Brooklyn, additional, Ahmad-Saeed, Nusreen, additional, Aldridge, Catherine, additional, Ambretti, Simone, additional, Amit, Sharon, additional, Annett, Rachel, additional, O'Shea, Shaan Ashk, additional, Barbui, Anna Maria, additional, Barlow, Gavin, additional, Barrett, Lucinda, additional, Berth, Mario, additional, Bondi, Alessandro, additional, Boran, Nicola, additional, Boyd, Sara E., additional, Chaves, Catarina, additional, Clauss, Martin, additional, Davies, Peter, additional, Dianzo-Delgado, Ileana T., additional, Esteban, Jaime, additional, Fuchs, Stefan, additional, Friis-Hansen, Lennart, additional, Goldenberger, Daniel, additional, Golle, Andrej, additional, Groonroos, Juha O., additional, Hoffmann, Ines, additional, Hoffmann, Tomer, additional, Hughes, Harriet, additional, Ivanova, Marina, additional, Jezek, Peter, additional, Jones, Gwennan, additional, Ceren Karahan, Zeynep, additional, Lass-Flörl, Cornelia, additional, Laurent, Frédéric, additional, Leach, Laura, additional, Horsbøll Pedersen, Matilde Lee, additional, Loiez, Caroline, additional, Lynch, Maureen, additional, Maloney, Robert J., additional, Marsh, Martin, additional, Milburn, Olivia, additional, Mitchell, Shanine, additional, Moore, Luke S. P., additional, Moffat, Lynn, additional, Murdjeva, Marianna, additional, Murphy, Michael E., additional, Nayar, Deepa, additional, Nigrisoli, Giacomo, additional, O'Sullivan, Fionnuala, additional, Öz, Büşra, additional, Peach, Teresa, additional, Petridou, Christina, additional, Prinz, Mojgan, additional, Rak, Mitja, additional, Reidy, Niamh, additional, Rossolini, Gian Maria, additional, Roux, Anne-Laure, additional, Ruiz-Garbajosa, Patricia, additional, Saeed, Kordo, additional, Salar-Vidal, Llanos, additional, Salas Venero, Carlos, additional, Selvaratnam, Mathyruban, additional, Senneville, Eric, additional, Starzengruber, Peter, additional, Talbot, Ben, additional, Taylor, Vanessa, additional, Trebše, Rihard, additional, Wearmouth, Deborah, additional, Willinger, Birgit, additional, Wouthuyzen-Bakker, Marjan, additional, Couturier, Brianne, additional, and Allantaz, Florence, additional

Published
2024
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46. Utility of bronchoalveolar lavage for COVID-19: a perspective from the Dragon consortium

Author

Tomassetti, Sara, primary, Ciani, Luca, additional, Luzzi, Valentina, additional, Gori, Leonardo, additional, Trigiani, Marco, additional, Giuntoli, Leonardo, additional, Lavorini, Federico, additional, Poletti, Venerino, additional, Ravaglia, Claudia, additional, Torrego, Alfons, additional, Maldonado, Fabien, additional, Lentz, Robert, additional, Annunziato, Francesco, additional, Maggi, Laura, additional, Rossolini, Gian Maria, additional, Pollini, Simona, additional, Para, Ombretta, additional, Ciurleo, Greta, additional, Casini, Alessandro, additional, Rasero, Laura, additional, Bartoloni, Alessandro, additional, Spinicci, Michele, additional, Munavvar, Mohammed, additional, Gasparini, Stefano, additional, Comin, Camilla, additional, Cerinic, Marco Matucci, additional, Peired, Anna, additional, Henket, Monique, additional, Ernst, Benoit, additional, Louis, Renaud, additional, Corhay, Jean-louis, additional, Nardi, Cosimo, additional, and Guiot, Julien, additional

Published
2024
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47. Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA)

Author

Paniagua-García, María, primary, Bravo-Ferrer, Jose M., additional, Pérez-Galera, Salvador, additional, Kostyanev, Tomislav, additional, de Kraker, Marlieke E.A., additional, Feifel, Jan, additional, Palacios-Baena, Zaira R., additional, Schotsman, Joost, additional, Cantón, Rafael, additional, Daikos, George L., additional, Carevic, Biljana, additional, Dragovac, Gorana, additional, Tan, Lionel K., additional, Raka, Lul, additional, Hristea, Adriana, additional, Viale, Pierluigi, additional, Akova, Murat, additional, Cano, Ángela, additional, Reguera, Jose María, additional, Bartoloni, Alessandro, additional, Florescu, Simin-Aysel, additional, Benea, Serban, additional, Bukarica, Ljiljana, additional, Asensio, Ángel, additional, Korten, Volkan, additional, Grundmann, Hajo, additional, Goossens, Herman, additional, Bonten, Marc J., additional, Gutiérrez-Gutiérrez, Belén, additional, Rodríguez-Baño, Jesús, additional, Serna, Almudena de la, additional, Monteau, Sophie, additional, Palomo, Virginia, additional, Soriano, Elena, additional, Gutierrez, David, additional, Moreno, Elisa, additional, Sojo-Dorado, Jesus, additional, Morales, Isabel, additional, Maldonado, Natalia, additional, Santis, Lucia Valiente de, additional, Ciezar, Antonio Plata, additional, Ruiz Mesa, Juan Diego, additional, Diaz, Beatriz Sobrino, additional, Gomez, Ignacio Marquez, additional, Camacho, Ines Perez, additional, Cano, Angela, additional, Frutos-Adame, Azahara, additional, Guzman-Puche, Julia, additional, Gracia-Ahufinger, Irene, additional, Perez-Nadales, Elena, additional, Torre-Gimenez, Julian, additional, Pyrpasopoulou, Athina, additional, Iosifidis, Elias, additional, Chorafa, Elsa, additional, Radovanovic, Ivana, additional, Petrovic, Sladjana, additional, Cvetkovi, Slavica, additional, Melentijevic, Srdjan-Sanja, additional, Bicmen, Can, additional, Senol, Gunes, additional, Tubau, Fe, additional, Camara, Jordi, additional, Daniel Gumucio, Victor, additional, Bassoulis, Dimitris, additional, Deliolanis, John, additional, Pitiriga, Vassiliki Ch., additional, Triarides, Nikolaos, additional, Argiti, Efstathia, additional, Legakis, Nikolaos J., additional, Margarita, Kyriakidou, additional, Gijón-Cordero, Desirée, additional, Ruiz-Garbajosa, Patricia, additional, Rossolini, Gian Maria, additional, Nica, Maria, additional, Talapan, Daniela, additional, Medić, Deana, additional, Prijić, Sanja Maričić, additional, Caballero, Mireia Cantero, additional, Ramírez, Lina M Parra, additional, Bilgin, Hüseyin, additional, Dalekos, George N., additional, Stefos, Aggelos, additional, Spyridis, Nikolaos, additional, Michos, Athanasios, additional, De Rosa, Francesco Giuseppe, additional, Cavallo, Rossana, additional, Petrosillo, Nicola, additional, Dicaro, Antonio, additional, Landini, Maria Paola, additional, degli Atti, Marta Luisa Ciofi, additional, Masanovic, Mileva, additional, Matkovic, Dusan, additional, Tsiodras, Sotirios, additional, Blasi, Francesco, additional, pasquale, Marta Di, additional, Viscoli, Claudio, additional, Vata, Andrei, additional, Dorneanu, Olivia, additional, Kapisyzi, Perlat, additional, Vince, Adriana, additional, Tsigou, Evdoxia, additional, Maltezos, Efstratios, additional, Komnos, Apostolos, additional, Gogos, Charalampos, additional, Franzetti, Fabio, additional, Antonelli, Massimo, additional, Lupse, Mihaela, additional, Corneci, Dan, additional, Tomescu, Dana, additional, Georgescu, Anca, additional, Mitrović, Goran, additional, Krstić, Nataša Lukić, additional, Kurti, Arsim, additional, Reuter, Sandra, additional, Díaz-Pollán, Beatriz, additional, Sabater, Julia Origüen, additional, Muñoz, Patricia, additional, Azap, Alpay, additional, ancak, Banu, additional, Sahin, Arife, additional, and Akalin, Halis, additional

Published
2024
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50. Multicenter study on the prevalence of colonization due to carbapenem-resistant Enterobacterales strains before and during the first year of COVID-19, Italy 2018–2020

Author

Fasciana, Teresa, primary, Antonelli, Alberto, additional, Bianco, Gabriele, additional, Lombardo, Donatella, additional, Codda, Giulia, additional, Roscetto, Emanuela, additional, Perez, Marianna, additional, Lipari, Dario, additional, Arrigo, Ignazio, additional, Galia, Elena, additional, Tricoli, Maria Rita, additional, Calvo, Maddalena, additional, Niccolai, Claudia, additional, Morecchiato, Fabio, additional, Errico, Giulia, additional, Stefani, Stefania, additional, Cavallo, Rossana, additional, Marchese, Anna, additional, Catania, Maria Rosaria, additional, Ambretti, Simone, additional, Rossolini, Gian Maria, additional, Pantosti, Annalisa, additional, Palamara, Anna Teresa, additional, Sabbatucci, Michela, additional, Serra, Nicola, additional, and Giammanco, Anna, additional

Published
2023
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