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1. Validation of the INCREMENT‐SOT‐CPE score in a large cohort of liver transplant recipients with carbapenem‐resistant Enterobacterales infection

Author

Rinaldi, Matteo, Bonazzetti, Cecilia, Gallo, Mena, Ferraro, Giuseppe, Freire, Maristela, Terrabuio, Débora Raquel Benedita, Tandoi, Francesco, Romagnoli, Renato, De Rosa, Francesco Giuseppe, Mularoni, Alessandra, Ferrarese, Alberto, Burra, Patrizia, Halpern, Marcia, Balbi, Elizabeth, Simkins, Jacques, Abbo, Lilian, Morrás, Ignacio, Cantero, Mireia, Alagna, Laura, Bandera, Alessandra, Clemente, Wanessa Trinidade, Valerio, Maricela, Fernández, Ainhoa, Muñoz, Patricia, Statlender, Liran, Yahav, Dafna, Camargo, Luis Fernando Aranha, Girão, Evelyne Santana, Grossi, Paolo, Viale, Pierluigi, Curti, Stefania, Giannella, Maddalena, Rinaldi M., Bonazzetti C., Gallo M., Ferraro G., Freire M., Terrabuio D.R.B., Tandoi F., Romagnoli R., De Rosa F.G., Mularoni A., Ferrarese A., Burra P., Halpern M., Balbi E., Simkins J., Abbo L., Morrás I., Cantero M., Alagna L., Bandera A., Clemente W.T., Valerio M., Fernández A., Muñoz P., Statlender L., Yahav D., Camargo L.F.A., Girão E.S., Grossi P., Viale P., Curti S., and Giannella M.

Subjects
INCREMENT-SOT-CPE score, Transplantation, Infectious Diseases, CRE infection, liver transplantation, SOT
Abstract

Background: Management of infections due to carbapenemase-resistant Enterobacterales (CRE) in solid organ transplant (SOT) recipients remains a difficult challenge. The INCREMENT-SOT-CPE score has been specifically developed from SOT recipients to stratify mortality risk, but an external validation is lacking.Methods: Multicenter retrospective cohort study of liver transplant (LT) recipients colonized with CRE infection who developed infection after transplant over 7-year period. Primary endpoint was all-cause 30-day mortality from infection onset. A comparison between INCREMENT-SOT-CPE and other selected scores was performed. A two-level mixed effects logistic regression model with random effects for the center was fitted. Performance characteristics at optimal cut-point were calculated. Multivariable Cox regression analysis of risk factors for all-cause 30-day mortality was carried out.Results: Overall, 250 CRE carriers developed infection after LT and were analyzed. The median age was 55 years (interquartile range [IQR]: 46-62) and 157 were males (62.8%). All-cause 30-day mortality was 35.6%. A sequential organ failure assessment (SOFA) score >= 11 showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 69.7%, 76.4%, 62.0%, 82.0%, and 74.0%, respectively. An INCREMENT-SOT-CPE >= 11 reported a sensitivity, specificity, PPV, NPV, and accuracy of 73.0%, 62.1%, 51.6%, 80.6% and 66.0%, respectively. At multivariable analysis acute renal failure, prolonged mechanical ventilation, INCREMENT-SOT-CPE score >= 11 and SOFA score >= 11 were independently associated with all-cause 30-day mortality, while a tigecycline-based targeted regimen was found to be protective.Conclusions: Both INCREMENT-SOT-CPE >= 11 and SOFA >= 11 were identified as strong predictors of all-cause 30-day mortality in a large cohort of CRE carriers developing infection after LT.

Published
2023

2. Zoonotic infectious diseases in transplanted immunocompromised patients

Author

Blanda Valeria, Mularoni Alessandra, Angelo, Luca, Federica, Bruno, Castelli Germano, Fabrizio, Vitale, D'agostino Rosalia, Grippi Francesca, and Alessandra, Torina

Subjects
bacteria, bacterial infections and mycoses
Abstract

Background. Immunocompromised patients, like transplant recipients, are a particularly vulnerable group being at higher risk of developing several infectious diseases. Among them, zoonotic diseases, such as visceral leishmaniasis, bartonellosis, Q fever and leptospirosis are a growing concern in immunosuppressed patients as they are more susceptible to develop severe symptoms of the diseases. Objectives. The study aimed at the detection of Leishmania infantum, Bartonella spp., Leptospira spp. and Coxiella burnetii DNA in immunocompromised hosts through molecular methods.

Published
2021
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3. Use of colistin in adult patients: a cross-sectional study

Author

Giacobbe, Daniele Roberto, Saffioti, Carolina, Losito, Angela Raffaella, Rinaldi, Matteo, Aurilio, Caterina, Bolla, Cesare, Boni, Silvia, Borgia, Guglielmo, Carannante, Novella, Cassola, Giovanni, Ceccarelli, Giancarlo, Corcione, Silvia, Gasperina, Daniela Dalla, De Rosa, Francesco Giuseppe, Dentone, Chiara, Di Bella, Stefano, Di Lauria, Nicoletta, Feasi, Marcello, Fiore, Marco, Fossati, Sara, Franceschini, Erica, Gori, Andrea, Granata, Guido, Grignolo, Sara, Grossi, Paolo Antonio, Guadagnino, Giuliana, Lagi, Filippo, Maraolo, Alberto Enrico, Marinò, Valeria, Mazzitelli, Maria, Mularoni, Alessandra, Oliva, Alessandra, Pace, Maria Caterina, Parisini, Andrea, Patti, Francesca, Petrosillo, Nicola, Pota, Vincenzo, Raffaelli, Francesca, Rossi, Marianna, Santoro, Antonella, Tascini, Carlo, Torti, Carlo, Trecarichi, Enrico Maria, Venditti, Mario, Viale, Pierluigi, Signori, Alessio, Del Bono, Valerio, Giannella, Maddalena, Mikulska, Malgorzata, Tumbarello, Mario, Viscoli, Claudio, Passavanti, Maria Beatrice, Rogati, C, Sansone, Pasquale, Sarteschi, G, Roberto Giacobbe, Daniele, Saffioti1, Carolina, Raffaella Losito, Angela, Rinaldi, Matteo, Aurilio, Caterina, Bolla, Cesare, Boni, Silvia, Borgia, Guglielmo, Carannante, Novella, Cassola, Giovanni, Ceccarelli, Giancarlo, Corcione, Silvia, Dalla Gasperina, Daniela, Giuseppe De Rosa, Francesco, Dentone, Chiara, DI BELLA, Stefano, Di Lauria, Nicoletta, Feasi, Marcello, Fiore, Marco, Fossati, Sara, Franceschini, Erica, Gori, Andrea, Granata, Guido, Grignolo, Sara, Antonio Grossi, Paolo, Guadagnino, Giuliana, Lagi, Filippo, Enrico Maraolo, Alberto, Marinò, Valeria, Mazzitelli, Maria, Mularoni, Alessandra, Oliva, Alessandra, Caterina Pace, Maria, Parisini, Andrea, Patti, Francesca, Petrosillo, Nicola, Pota, Vincenzo, Raffaelli, Francesca, Rossi, Marianna, Santoro, Antonella, Tascini, Carlo, Torti, Carlo, Maria Trecarichi, Enrico, Venditti, Mario, Viale, Pierluigi, Signori, Alessio, Bassetti, Matteo, Del Bono, Valerio, Giannella, Maddalena, Mikulska, Malgorzata, Tumbarello, Mario, Viscoli, Claudio, Giacobbe, Daniele Roberto, Saffioti, Carolina, Losito, Angela Raffaella, Gasperina, Daniela Dalla, De Rosa, Francesco Giuseppe, Di Bella, Stefano, Grossi, Paolo Antonio, Maraolo, Alberto Enrico, Pace, Maria Caterina, Trecarichi, Enrico Maria, Passavanti, Maria Beatrice, Rogati, C, Sansone, Pasquale, Sarteschi, G, Giacobbe D.R., Saffioti C., Losito A.R., Rinaldi M., Aurilio C., Bolla C., Boni S., Borgia G., Carannante N., Cassola G., Ceccarelli G., Corcione S., Dalla Gasperina D., De Rosa F.G., Dentone C., Di Bella S., Di Lauria N., Feasi M., Fiore M., Fossati S., Franceschini E., Gori A., Granata G., Grignolo S., Grossi P.A., Guadagnino G., Lagi F., Maraolo A.E., Marino V., Mazzitelli M., Mularoni A., Oliva A., Pace M.C., Parisini A., Patti F., Petrosillo N., Pota V., Raffaelli F., Rossi M., Santoro A., Tascini C., Torti C., Trecarichi E.M., Venditti M., Viale P., Signori A., Bassetti M., Del Bono V., Giannella M., Mikulska M., Tumbarello M., and Viscoli C.

Subjects
0301 basic medicine, Male, Endemic Diseases, Drug Resistance, Carbapenem-resistant enterobacteriaceae, Pseudomona, 0302 clinical medicine, Interquartile range, Levofloxacin, Drug Resistance, Multiple, Bacterial, Klebsiella, polycyclic compounds, Acinetobacter, Antimicrobial resistance, Colistimethate, Colistin, Pseudomonas, Administration, Intravenous, Aged, Anti-Bacterial Agents, Cross-Sectional Studies, Drug Prescriptions, Drug Therapy, Combination, Female, Gram-Negative Bacterial Infections, Humans, Italy, Middle Aged, Respiratory Tract Infections, Sepsis, Immunology and Allergy, 030212 general & internal medicine, colistin, colistimethate, Bacterial, QR1-502, Administration, Combination, lipids (amino acids, peptides, and proteins), antimicrobial resistance, Intravenous, Multiple, medicine.drug, Microbiology (medical), medicine.medical_specialty, Cefepime, 030106 microbiology, Immunology, Microbiology, Loading dose, 03 medical and health sciences, Drug Therapy, Internal medicine, Lower respiratory tract infection, medicine, business.industry, biochemical phenomena, metabolism, and nutrition, medicine.disease, business
Abstract

Objectives The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB). Methods Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed. Results A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52–73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24–8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69–13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17–0.88; P = 0.024) was associated with use of colistin monotherapy. Conclusion Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.

Published
2020

4. Ceftazidime-avibactam use for KPC-Kp infections: a retrospective observational multicenter study

Author

Tumbarello, Mario, Raffaelli, Francesca, Giannella, Maddalena, Mantengoli, Elisabetta, Mularoni, Alessandra, Venditti, Mario, De Rosa, Francesco Giuseppe, Sarmati, Loredana, Bassetti, Matteo, Brindicci, Gaetano, Rossi, Marianna, Luzzati, Roberto, Grossi, Paolo Antonio, Corona, Alberto, Capone, Alessandro, Falcone, Marco, Mussini, Cristina, Trecarichi, Enrico Maria, Cascio, Antonio, Guffanti, Elena, Russo, Alessandro, De Pascale, Gennaro, Tascini, Carlo, Gentile, Ivan, Losito, Angela Raffaella, Bussini, Linda, Conti, Giampaolo, Ceccarelli, Giancarlo, Corcione, Silvia, Compagno, Mirko, Giacobbe, Daniele Roberto, Saracino, Annalisa, Fantoni, Massimo, Antinori, Spinello, Peghin, Maddalena, Bonfanti, Paolo, Oliva, Alessandra, De Gasperi, Andrea, Tiseo, Giusy, Rovelli, Cristina, Meschiari, Marianna, Shbaklo, Nour, Spanu, Teresa, Cauda, Roberto, Viale, Pierluigi, Tumbarello, M, Raffaelli, F, Giannella, M, Mantengoli, E, Mularoni, A, Venditti, M, De Rosa, F, Sarmati, L, Bassetti, M, Brindicci, G, Rossi, M, Luzzati, R, Grossi, P, Corona, A, Capone, A, Falcone, M, Mussini, C, Trecarichi, E, Cascio, A, Guffanti, E, Russo, A, De Pascale, G, Tascini, C, Gentile, I, Losito, A, Bussini, L, Conti, G, Ceccarelli, G, Corcione, S, Compagno, M, Giacobbe, D, Saracino, A, Fantoni, M, Antinori, S, Peghin, M, Bonfanti, P, Oliva, A, De Gasperi, A, Tiseo, G, Rovelli, C, Meschiari, M, Shbaklo, N, Spanu, T, Cauda, R, and Viale, P

Subjects
Carbapenemase, carbapenemases, Ceftazidime-avibactam, ceftazidime-avibactam, KPC-producing Klebsiella pneumoniae
Abstract

Background: A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. Methods: We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. Results: The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P =. 79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock (P =. 002), neutropenia (P

Published
2021

5. Efficacy of Ceftazidime-avibactam Salvage Therapy in Patients with Infections Caused by KPC-producing Klebsiella pneumoniae

Author

Tumbarello, Mario, Trecarichi, Enrico Maria, Corona, Alberto, De Rosa, Francesco Giuseppe, Bassetti, Matteo, Mussini, Cristina, Menichetti, Francesco, Viscoli, Claudio, Campoli, Caterina, Venditti, Mario, De Gasperi, Andrea, Mularoni, Alessandra, Tascini, Carlo, Parruti, Giustino, Pallotto, Carlo, Sica, Simona, Concia, Ercole, Cultrera, Rosario, De Pascale, Gennaro, Capone, Alessandro, Antinori, Spinello, Corcione, Silvia, Righi, Elda, Losito, Angela Raffaella, Digaetano, Margherita, Amadori, Francesco, Giacobbe, Daniele Roberto, Ceccarelli, Giancarlo, Mazza, Ernestina, Raffaelli, Francesca, Spanu, Teresa, Cauda, Roberto, and Viale, Pierluigi

Subjects
KPC-Kp infections, urinary-tract infections, KPC-Kp infections, Ceftazidime-avibactam (CAZ-AVI), Settore MED/17 - MALATTIE INFETTIVE, Ceftazidime-avibactam (CAZ-AVI), Gram-negative
Published
2019

6. Successful Treatment of KSHV Inflammatory Cytokine Syndrome (KICS) after Kidney-Liver Transplant: Correlations with HHV8 miRNome and Specific T-Cell Response

Author

Mularoni, Alessandra, Gallo, Alessia, Riva, Giovanni, Barozzi, Patrizia, Miele, Monica, Cardinale, Giovanni, Vizzini, Giovanni, Volpes, Riccardo, Grossi, Paolo, Di Carlo, Daniele, Luca, Angelo, Trenti, Tommaso, Luppi, Mario, and Conaldi, Pier Giulio

Subjects
KSHV inflammatory cytokine syndrome [KICS], micro-RNA, post-transplant KICS, HHV-8, KSHV inflammatory cytokine syndrome, micro-RNA [KICS]
Published
2017

7. Cytomegalovirus infection management in solid organ transplant recipients across European centers in the time of molecular diagnostics: An ESGICH survey

Author

Navarro, David, San-Juan, Rafael, Manuel, Oriol, Gimã©nez, Estela, Fernández-Ruiz, Mario, Hirsch, Hans H., Grossi, Paolo Antonio, Aguado, José María, Abram, Maja, Abramowicz, Daniel, Álamo, José-María, Alp, Sehnaz, Andres-Belmonte, Amado, Anne-Catherine, Pouleur, Antonelli, Barbara, Arnol, Miha, Arslan, Ayse Hande, Asderakis, Argiris, Baldanti, Fausto, Beneyto-Castello, Isabel, Benoit, Kabamba Mukadi, Blanes, Marino, Boggian, Katia, Bonofiglio, Renzo, Bubonja-Sonje, Marina, Caillard, Sophie, Calvo, Jorge, Capone, Alessandro, Cappelli, Gianni, Carmellini, Mario, Casafont, Fernando, Beatriz Castro-Hernandez, M., Catalan, Pilar, Celine, Bressollette-Bodin, Christoph, Berger, Cordero, Elisa, Costa, Cristina, Coussement, Julien, Cuervas-Mons, Valentin, David, Miruna, de la Torre Cisneros, Juliã¡n, Delgado, Juan F., Dello Strologo, Luca, Detry, Olivier, Dexter, Laura, Dieter, Hoffmann, Meis-Hübinger, Anna, Epailly, Eric, Ericzon, Bo-Goran, Eriksson, Britt-Marie, Fehervari, Imre, Fitzgerald, Susan, Folgueira, Lola, Fortun, Jesus, Franceschini, Erica, Francois, Proot, Friman, Vanda, Frimmel, Silvius, Garzoni, Christian, Gimeno, Adelina, Gkrania-Klotsas, Effrossyni, Greer, Mark, Griffiths, Paul, Grinyã³, Josep M., Guaraldi, Giovanni, Gupte, Girish, Hammad, Abdul, Hart, Ian, Helanterã¤, Ilkka, Hellemans, Rachel, Hernã¡ndez, Domingo, Herrero, Jose Ignacio, Hiesse, Christian, Hoppe-Lotichius, Maria, Hryniewiecka, Ewa, Jaksch, Peter, Jan, Lerut, Paul, Brion Jean, Jensen-Fangel, Soren, Joerg, Steinmann, Johan, Vanhaecke, Johannessen, Ingolfur, Johansson, Inger, Kamar, Nassim, Kizilates, Filiz, Knoop, Christiane, Laurent, Belec, Lauro, Augusto, Lautenschlager, Irmeli, Lauzurica, Ricardo, Liebert, U. G., dela Monica, Paolalilla, Llado, Laura, Lopez-Andujar, Rafael, Luciani, Filippo, Maccherini, Massimo, Maertens, Johan, Maggiore, Umberto, Manrique, Alejandro, Marcos, Maria Angeles, Marekovic, Ivana, Marques, Nuno, Martin, Nitschke, Martine, Neau, Martinez-Sapiña, Ana, Mateos Lindemann, M. Luisa, Mazuecos, Auxiliadora, Merino, Esperanza, Moreso, Francesc, Mueller, Nicolas, Muir, David, Mularoni, Alessandra, Muã±oz, Patricia, Muñoz-Sanz, Agustã­n, Nadalin, Silvio, Laura Ambra, Nicolini, Nosotti, Mario, Gorman, Joanne O., Osman, Husam, Padalko, Elizaveta, Palop-Borrás, Begoã±a, Javirparmer, Null, Pascual, Sonia, Pena López, María José, Pérez-Sáenz, José Luis, Pistello, Mauro, Francisca Portero, M., Puchhammer, Elisabeth, Racca, Sara, Rahamat-Langendoen, Janette, Ramos, Antonio, Boluda, Esther Ramos, Raza, Mohammad, Regalia, Enrico, Reina, Gabriel, Reischig, Tomas, Reuter, Stefan, Rodríguez-Ferrero, M. Luisa, Roilides, Emmanuel, Rolla, Serena, Rollag, Halvor, Rostaing, Lionel, Russo, Francesco Paolo, Sabã©, Nãºria, Saliba, Faouzi, Sánchez-Fructuoso, Ana, Scotton, Giorgio, Serra, Nuria, Sgarabotto, Dino, Stojanovic, Jelena, Tasbakan, Meltem, Telenti, Mauricio, Terhes, Gabriella, Thorban, Stefan, Tihic, Nijaz, Travi, Giovanna, Tulissi, Patrizia, Van Delden, Christian, Van Leer, Coretta, Van Loo, Inge, Varona-Bosque, María Aránzazu, Veroux, Massimiliano, Vila-Santandreu, Ana, Waugh, Sheila, Zibar, Lada, and Zschiedr, Stefan

Subjects
0301 basic medicine, cytomegalovirus, solid organ transplantation, survey, Cross-sectional study, Cytomegalovirus, Transplants, Practice Patterns, 030230 surgery, Organ transplantation, law.invention, 0302 clinical medicine, Postoperative Complications, law, 03.02. Klinikai orvostan, Viral, Practice Patterns, Physicians', Polymerase chain reaction, Viral Load, Europe, Infectious Diseases, Cytomegalovirus Infections, Practice Guidelines as Topic, Antibiotic Prophylaxis, Antiviral Agents, Cross-Sectional Studies, DNA, Viral, Guideline Adherence, Health Care Surveys, Humans, Immunocompromised Host, Immunosuppression, Organ Transplantation, Real-Time Polymerase Chain Reaction, Transplant Recipients, Transplantation, medicine.medical_specialty, 030106 microbiology, Congenital cytomegalovirus infection, 03 medical and health sciences, medicine, Intensive care medicine, Immunosuppression Therapy, Physicians', business.industry, DNA, medicine.disease, Molecular diagnostics, Cytomegalovirus infection, Solid organ transplantation, Survey, Immunology, business
Abstract

Background Scant information is available about how transplant centers are managing their use of quantitative molecular testing (QNAT) assays for active cytomegalovirus (CMV) infection monitoring in solid organ transplant (SOT) recipients. The current study was aimed at gathering information on current practices in the management of CMV infection across European centers in the era of molecular testing assays. Methods A questionnaire-based cross-sectional survey study was conducted by the European Study Group of Infections in Immunocompromised Hosts (ESGICH) of the Society of Clinical Microbiology and Infectious Diseases (ESCMID). The invitation and a weekly reminder with a personal link to an internet service provider (h t t p s://es.surveymonkey. com/) was sent to transplant physicians, transplant infectious diseases specialists, and clinical virologists working at 340 European transplant centers. Results Of the 1181 specialists surveyed, a total of 173 responded (14.8%): 73 transplant physicians, 57 transplant infectious diseases specialists, and 43 virologists from 173 institutions located at 23 different countries. The majority of centers used QNAT assays for active CMV infection monitoring. Most centers preferred commercially-available real-time polymerase chain reaction (RT-PCR) assays over laboratory-developed procedures for quantifying CMV DNA load in whole blood or plasma. Use of a wide variety of DNA extraction platforms and RT-PCR assays was reported. All programs used antiviral prophylaxis, preemptive therapy, or both, according to current guidelines. However, the centers used different criteria for starting preemptive antiviral treatment, for monitoring systemic CMV DNA load, and for requesting genotypic assays to detect emerging CMV-resistant variants. Conclusions Significant variation in CMV infection management in SOT recipients still remains across European centers in the era of molecular testing. International multicenter studies are required to achieve commutability of CMV testing and antiviral management procedures. This article is protected by copyright. All rights reserved.

Published
2017

8. Molecular Analysis With 16S rRNA PCR/Sanger Sequencing and Molecular Antibiogram Performed on DNA Extracted From Valve Improve Diagnosis and Targeted Therapy of Infective Endocarditis: A Prospective Study

Author

Alessandra Mularoni, Malgorzata Mikulska, Floriana Barbera, Elena Graziano, Alice Annalisa Medaglia, Daniele Di Carlo, Francesco Monaco, Diego Bellavia, Antonio Cascio, Giuseppe Raffa, Sergio Sciacca, Angelo Luca, Michele Pilato, Pier Giulio Conaldi, Mularoni, Alessandra, Mikulska, Malgorzata, Barbera, Floriana, Graziano, Elena, Medaglia, Alice Annalisa, Di Carlo, Daniele, Monaco, Francesco, Bellavia, Diego, Cascio, Antonio, Raffa, Giuseppe, Sciacca, Sergio, Luca, Angelo, Pilato, Michele, and Conaldi, Pier Giulio

Subjects
16 s and 18 s rRNA, Microbiology (medical), blood culture negative endocarditi, Infectious Diseases, molecular antibiogram, molecular analysi
Abstract

Background Molecular analysis (MA) on heart valve (HV) improves the microbiologic diagnosis of infectious endocarditis (IE). The main drawback of MA is the lack of antimicrobial susceptibility information. Methods We conducted a prospective cohort observational study of consecutive adult patients from April 2012 to May 2021 who underwent valve surgery at our hospital. The performance of MA, blood cultures (BC) and valve cultures (VC), and the diagnostic and therapeutic impact of MA were evaluated. Molecular antibiogram results were compared to culture-based antimicrobial susceptibility testing (AST). Results A total of 137 patients with definite IE and 52 patients with no IE were enrolled in the study. Among IE cases BC, VC, and MA were positive in 75 (55%), 30 (22%), and 120 (88%) of IE cases, respectively. Among 62 cases of BC-negative IE (BCNE), 57 achieved diagnosis with MA. MA led to a change of antimicrobial therapy in 92% of BCNE. MA was negative in 100% of patients with no IE. Molecular antibiogram performed on 17 valve specimens that resulted positive for pathogens potential carrier of genes encoding for multidrug resistant mechanisms showed 100% concordance with AST. Conclusions MA showed a high specificity and sensitivity in etiological diagnosis of IE. Molecular antibiogram could overcome the major limitation of MA that is the lack of susceptibility testing. We advocate for the inclusion of MA among diagnostic criteria for IE and for a more extensive use of molecular antibiogram when the culture result is negative, and MA is the only positive test.

Published
2022

9. Ceftazidime-avibactam use for klebsiella pneumoniae carbapenemase-producing k. pneumoniae infections: A retrospective observational multicenter study

Author

Mirko Compagno, Giampaolo Corti, Maddalena Peghin, Francesca Raffaelli, Annalisa Saracino, Cristina Mussini, Spinello Antinori, Maddalena Giannella, Roberto Cauda, Marianna Rossi, Gennaro De Pascale, Elena Guffanti, Enrico Maria Trecarichi, Giancarlo Ceccarelli, Teresa Spanu, Elisabetta Mantengoli, Antonio Cascio, Mario Venditti, Loredana Sarmati, Carlo Tascini, Silvia Corcione, Daniele Roberto Giacobbe, Massimo Fantoni, Linda Bussini, Paolo Bonfanti, Alessandra Mularoni, Marianna Meschiari, Nour Shbaklo, Giusy Tiseo, Mario Tumbarello, Roberto Luzzati, Angela Raffaella Losito, Alessandra Oliva, Pierluigi Viale, Alessandro Russo, Francesco Giuseppe De Rosa, Gaetano Brindicci, Ivan Gentile, Alberto Corona, Andrea De Gasperi, Paolo Grossi, Marco Falcone, Alessandro Capone, Cristina Rovelli, Matteo Bassetti, Tumbarello M., Raffaelli F., Giannella M., Mantengoli E., Mularoni A., Venditti M., De Rosa F.G., Sarmati L., Bassetti M., Brindicci G., Rossi M., Luzzati R., Grossi P.A., Corona A., Capone A., Falcone M., Mussini C., Trecarichi E.M., Cascio A., Guffanti E., Russo A., De Pascale G., Tascini C., Gentile I., Losito A.R., Bussini L., Corti G., Ceccarelli G., Corcione S., Compagno M., Giacobbe D.R., Saracino A., Fantoni M., Antinori S., Peghin M., Bonfanti P., Oliva A., De Gasperi A., Tiseo G., Rovelli C., Meschiari M., Shbaklo N., Spanu T., Cauda R., Viale P., Tumbarello, Mario, Raffaelli, Francesca, Giannella, Maddalena, Mantengoli, Elisabetta, Mularoni, Alessandra, Venditti, Mario, De Rosa, Francesco Giuseppe, Sarmati, Loredana, Bassetti, Matteo, Brindicci, Gaetano, Rossi, Marianna, Luzzati, Roberto, Grossi, Paolo Antonio, Corona, Alberto, Capone, Alessandro, Falcone, Marco, Mussini, Cristina, Trecarichi, Enrico Maria, Cascio, Antonio, Guffanti, Elena, Russo, Alessandro, De Pascale, Gennaro, Tascini, Carlo, Gentile, Ivan, Losito, Angela Raffaella, Bussini, Linda, Conti, Giampaolo, Ceccarelli, Giancarlo, Corcione, Silvia, Compagno, Mirko, Giacobbe, Daniele Roberto, Saracino, Annalisa, Fantoni, Massimo, Antinori, Spinello, Peghin, Maddalena, Bonfanti, Paolo, Oliva, Alessandra, De Gasperi, Andrea, Tiseo, Giusy, Rovelli, Cristina, Meschiari, Marianna, Shbaklo, Nour, Spanu, Teresa, Cauda, Roberto, and Viale, Pierluigi

Subjects
Microbiology (medical), Adult, medicine.medical_specialty, Azabicyclo Compound, carbapenemases, Bacterial Protein, Microbial Sensitivity Tests, Neutropenia, Ceftazidime, beta-Lactamases, beta-Lactamase, Carbapenemase, carbapenemase, Bacterial Proteins, Retrospective Studie, Lower respiratory tract infection, Internal medicine, Drug Combination, Anti-Bacterial Agent, medicine, Humans, KPC-producing Klebsiella pneumoniae, Retrospective Studies, Septic shock, business.industry, Ceftazidime-avibactam, Microbial Sensitivity Test, ceftazidime-avibactam, Mortality rate, Carbapenemases, Anti-Bacterial Agents, Azabicyclo Compounds, Drug Combinations, Klebsiella Infections, Klebsiella pneumoniae, medicine.disease, Ceftazidime/avibactam, Settore MED/17, Infectious Diseases, Cohort, Propensity score matching, Observational study, business, medicine.drug, Human, Klebsiella Infection
Abstract

Background A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. Methods We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase–producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. Results The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P = .79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock (P = .002), neutropenia (P < .001), or an INCREMENT score ≥8 (P = .01); with lower respiratory tract infection (LRTI) (P = .04); and with CAZ-AVI dose adjustment for renal function (P = .01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P = .006). All associations remained significant after propensity score adjustment. Conclusions CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug’s seemingly more limited efficacy in LRTIs and potential survival benefits of prolonging CAZ-AVI infusions to ≥3 hours.

Published
2021

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

Author

Erica Franceschini, Malgorzata Mikulska, Andrea Lombardi, Gregorio Basile, Laura Isabella Lupo, Giambattista Lobreglio, Daniele Roberto Giacobbe, Giancarlo Ceccarelli, Maria Adriana Cataldo, Anna Maria De Luca, Mario Venditti, Stefano Di Bella, Emanuela Caraffa, Michele Bartoletti, Enrica Giacometti, Nicola Petrosillo, Matteo Bassetti, Alessandra Oliva, Guido Granata, Ivan Gentile, Pierluigi Viale, Cristina Mussini, Alessandro Pandolfo, Paolo Bonfanti, Raffaella Borromeo, Sara Fossati, Alessandra Mularoni, Lucia Adamoli, Fabrizio Ingrassia, Filippo Lagi, Alberto Enrico Maraolo, Carlotta Rogati, Filippo Trapani, Roberto Luzzati, Alessandro Bartoloni, Mario U. Mondelli, Granata, G, Petrosillo, N, Adamoli, L, Bartoletti, M, Bartoloni, A, Basile, G, Bassetti, M, Bonfanti, P, Borromeo, R, Ceccarelli, G, De Luca, A, Di Bella, S, Fossati, S, Franceschini, E, Gentile, I, Giacobbe, D, Giacometti, E, Ingrassia, F, Lagi, F, Lobreglio, G, Lombardi, A, Lupo, L, Luzzati, R, Maraolo, A, Mikulska, M, Mondelli, M, Mularoni, A, Mussini, C, Oliva, A, Pandolfo, A, Rogati, C, Trapani, F, Venditti, M, Viale, P, Caraffa, E, Cataldo, M, Granata, Guido, Petrosillo, Nicola, Adamoli, Lucia, Bartoletti, Michele, Bartoloni, Alessandro, Basile, Gregorio, Bassetti, Matteo, Bonfanti, Paolo, Borromeo, Raffaella, Ceccarelli, Giancarlo, De Luca, Anna Maria, Di Bella, Stefano, Fossati, Sara, Franceschini, Erica, Gentile, Ivan, Giacobbe, Daniele Roberto, Giacometti, Enrica, Ingrassia, Fabrizio, Lagi, Filippo, Lobreglio, Giambattista, Lombardi, Andrea, Lupo, Laura Isabella, Luzzati, Roberto, Maraolo, Alberto Enrico, Mikulska, Malgorzata, Mondelli, Mario Umberto, Mularoni, Alessandra, Mussini, Cristina, Oliva, Alessandra, Pandolfo, Alessandro, Rogati, Carlotta, Trapani, Filippo Fabio, Venditti, Mario, Viale, Pierluigi, Caraffa, Emanuela, Cataldo, Maria Adriana, Granata G., Petrosillo N., Adamoli L., Bartoletti M., Bartoloni A., Basile G., Bassetti M., Bonfanti P., Borromeo R., Ceccarelli G., De Luca A.M., Di Bella S., Fossati S., Franceschini E., Gentile I., Giacobbe D.R., Giacometti E., Ingrassia F., Lagi F., Lobreglio G., Lombardi A., Lupo L.I., Luzzati R., Maraolo A.E., Mikulska M., Mondelli M.U., Mularoni A., Mussini C., Oliva A., Pandolfo A., Rogati C., Trapani F.F., Venditti M., Viale P., Caraffa E., and Cataldo M.A.

Subjects
medicine.medical_specialty, recurrence, genetic structures, lcsh:Medicine, Logistic regression, Clostridioides difficile, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, risk factors, 030212 general & internal medicine, Risk factor, Prospective cohort study, 0303 health sciences, Adult patients, 030306 microbiology, business.industry, Incidence (epidemiology), Mortality rate, lcsh:R, General Medicine, risk factor, outcome, incidence, business, Clostridioides, Cohort study
Abstract

Background: Limited and wide-ranging data are available on the recurrent Clostridioides difficile infection (rCDI) incidence rate. Methods: We performed a cohort study with the aim to assess the incidence of and risk factors for rCDI. Adult patients with a first CDI, hospitalized in 15 Italian hospitals, were prospectively included and followed-up for 30 d after the end of antimicrobial treatment for their first CDI. A case–control study was performed to identify risk factors associated with 30-day onset rCDI. Results: Three hundred nine patients with a first CDI were included in the study, 32% of the CDI episodes (99/309) were severe/complicated, complete follow-up was available for 288 patients (19 died during the first CDI episode, and 2 were lost during follow-up). At the end of the study, the crude all-cause mortality rate was 10.7% (33 deaths/309 patients). Two hundred seventy-one patients completed the follow-up, rCDI occurred in 21% of patients (56/271) with an incidence rate of 72/10,000 patient-days. Logistic regression analysis identified exposure to cephalosporin as an independent risk factor associated with rCDI (RR: 1.7, 95% CI: 1.1–2.7, p = 0.03). Conclusion: Our study confirms the relevance of rCDI in terms of morbidity and mortality and provides a reliable estimation of its incidence.

Published
2020

11. Guillain-Barré syndrome after orthotopic liver transplantation: A clinical manifestation of immune reconstitution inflammatory syndrome?

Author

Ioannis Petridis, Vincenzina Lo Re, Gianvincenzo Sparacia, Mariapina Milazzo, Angelo Luca, Salvatore Gruttadauria, Alessandra Mularoni, Gaetano Burgio, Saša A. Živković, Riccardo Volpes, Lo Re, Vincenzina, Petridis, Ioanni, Živković, Saša, Burgio, Gaetano, Mularoni, Alessandra, Milazzo, Mariapina, Sparacia, Gianvincenzo, Volpes, Riccardo, Luca, Angelo, and Gruttadauria, Salvatore

Subjects
medicine.medical_treatment, Liver transplantation, Guillain-Barre Syndrome, Tacrolimus, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immune reconstitution inflammatory syndrome, medicine, Humans, Acute demyelinating polyneuropathy, Immunosuppression Therapy, Inflammation, Guillain-Barre syndrome, business.industry, Immunosuppression, General Medicine, medicine.disease, Guillain-Barré syndrome, Pathophysiology, Tacrolimu, Immunology, Surgery, Female, Neurology (clinical), Complication, business, 030217 neurology & neurosurgery
Abstract

Guillain-Barrè Syndrome, as part of the spectrum of dysimmune neuropathies, is unexpected to occur in immunocompromised hosts. We describe a clinical case of Guillain-Barrè syndrome, occurred a few weeks after a liver transplant, and we postulate that our case would satisfy all requirements to explain this peripheral nervous system complication as a clinical manifestation of an Immune reconstitution inflammatory syndrome. In this setting of liver transplantation, complicated by potentially multiple infective triggers, reduction of immunosuppression and reversal of pathogen-induced immunosuppression, through antimicrobial therapy, may have led to pro-inflammatory response. The pro-inflammatory pattern would have sustained the pathophysiologic mechanism of this immune neuropathy.

Published
2018

12. Infections in liver and lung transplant recipients. A national prospective cohort

Author

Gagliotti, Carlo, Morsillo, Filomena, Moro, Maria Luisa, Masiero, Lucia, Procaccio, Francesco, Vespasiano, Francesca, Pantosti, Annalisa, Monaco, Monica, Errico, Giulia, Ricci, Andrea, Grossi, Paolo, Nanni Costa, Alessandro, Adorno, D., Ambretti, S., Amoroso, A., Arghittu, M., Berloco, P., Bertani, A., Bonizzoli, M., Cambieri, P., Canzonieri, M., Caprio, M., Carrara, E., Carrinola, R., Cibelli, E., Cillo, U., Colledan, M., Colombo, R., Coluccio, E., Conaldi, P. G., Cusi, M., D’Armini, A. M., da Riva, A., D’Auria, B., de Carlis, L., de Cillia, C., de Gasperi, A., Di Caro, A., Di Ciaccio, P., Dondossola, D., Farina, C., Feltrin, G., Finarelli, A. C., Fossati, L., Gaibani, P., Garcia Fernandez, A., Gesu, G., Giacometti, R., Gona, F., Gridelli, B., Henrici de Angelis, L., Landini, M. P., Maldarelli, F., Mancini, C., Marone, P., Mularoni, A., Paglialunga, G., Paladini, P., Palù, G., Parisi, S., Peris, A., Pinna, A. D., Platto, M., Pugliese, F., Puoti, F., Rago, C., Ravini, M., Rea, F., Rinaldi, M., Rossi, G., Rossi, L., Rossi, M., Salizzoni, M., Sangiorgi, G., Santambrogio, L., Spada, M., Sparacino, V., Stella, F., Torelli, R., Torresani, E., Tosi, D., Vailati, F., Valeri, M., Venuta, F., Vesconi, S., Viale, P., Vismara, C., Gagliotti, C, Morsillo, F, Moro, M, Masiero, L, Procaccio, F, Vespasiano, F, Pantosti, A, Monaco, M, Errico, G, Ricci, A, Grossi, P, Nanni Costa, A, Adorno, D, Ambretti, S, Amoroso, A, Arghittu, M, Berloco, P, Bertani, A, Bonizzoli, M, Cambieri, P, Canzonieri, M, Caprio, M, Carrara, E, Carrinola, R, Cibelli, E, Cillo, U, Colledan, M, Colombo, R, Coluccio, E, Conaldi, P, Cusi, M, D’Armini, A, da Riva, A, D’Auria, B, de Carlis, L, de Cillia, C, de Gasperi, A, Di Caro, A, Di Ciaccio, P, Dondossola, D, Farina, C, Feltrin, G, Finarelli, A, Fossati, L, Gaibani, P, Garcia Fernandez, A, Gesu, G, Giacometti, R, Gona, F, Gridelli, B, Henrici de Angelis, L, Landini, M, Maldarelli, F, Mancini, C, Marone, P, Mularoni, A, Paglialunga, G, Paladini, P, Palù, G, Parisi, S, Peris, A, Pinna, A, Platto, M, Pugliese, F, Puoti, F, Rago, C, Ravini, M, Rea, F, Rinaldi, M, Rossi, G, Rossi, L, Rossi, M, Salizzoni, M, Sangiorgi, G, Santambrogio, L, Spada, M, Sparacino, V, Stella, F, Torelli, R, Torresani, E, Tosi, D, Vailati, F, Valeri, M, Venuta, F, Vesconi, S, Viale, P, Vismara, C, Gagliotti, Carlo, Morsillo, Filomena, Moro, Maria Luisa, Masiero, Lucia, Procaccio, Francesco, Vespasiano, Francesca, Pantosti, Annalisa, Monaco, Monica, Errico, Giulia, Ricci, Andrea, Grossi, Paolo, Costa, Alessandro Nanni, Adorno, Domenico, Ambretti, Simone, Amoroso, Antonio, Arghittu, Milena, Berloco, Pasquale, Bertani, Alessandro, Bonizzoli, Manuela, Cambieri, Patrizia, Canzonieri, Marco, Caprio, Mario, Carrara, Elena, Carrinola, Rosaria, Cibelli, Eva, Cillo, Umberto, Colledan, Michele, Colombo, Rosaria, Coluccio, Elena, Conaldi, Pier Giulio, Cusi, Mariagrazia, D’Armini, Andrea Maria, Da Riva, Adelaide, D'Auria, Bianca, De Carlis, Luciano, De Cillia, Carlo, De Gasperi, Andrea, Di Caro, Antonino, Di Ciaccio, Paola, Dondossola, Daniele, Farina, Claudio, Feltrin, Giuseppe, Finarelli, Alba Carola, Fossati, Lucina, Gaibani, Paolo, Fernandez, Aurora Garcia, Gesu, Giovanni, Giacometti, Raffaella, Gona, Floriana, Gridelli, Bruno, De Angelis, Lucia Henrici, Landini, Maria Paola, Maldarelli, Federica, Mancini, Carlo, Marone, Piero, Mularoni, Alessandra, Paglialunga, Giulia, Paladini, Piero, Palù, Giorgio, Parisi, Saverio, Peris, Adriano, Pinna, Antonio Daniele, Platto, Marco, Pugliese, Francesco, Puoti, Francesca, Rago, Claudio, Ravini, Mario, Rea, Federico, Rinaldi, Mauro, Rossi, Giorgio, Rossi, Lucia, Rossi, Massimo, Salizzoni, Mauro, Sangiorgi, Gabriela, Santambrogio, Luigi, Spada, Marco, Sparacino, Vito, Stella, Franco, Torelli, Rosanna, Torresani, Erminio, Tosi, Davide, Vailati, Francesca, Valeri, Maurizio, Venuta, Federico, Vesconi, Sergio, Viale, Pierluigi, and Vismara, Chiara

Subjects
Microbiology (medical), Infectious Diseases, Male, 0301 basic medicine, medicine.medical_treatment, Drug Resistance, Transplant Recipient, 030230 surgery, Liver transplantation, Postoperative Complications, 0302 clinical medicine, Drug Resistance, Multiple, Bacterial, Medicine, Cumulative incidence, Prospective Studies, Prospective cohort study, Incidence, Incidence (epidemiology), Mortality rate, Bacterial, Bacterial Infections, General Medicine, Middle Aged, lung transplant, Anti-Bacterial Agents, infectious, Italy, Female, Multiple, Adult, Bacteria, Humans, Transplant Recipients, Liver Transplantation, Lung Transplantation, Human, medicine.medical_specialty, 030106 microbiology, Bacterial Infection, Infectious Diseases, transplantation, 03 medical and health sciences, Internal medicine, Anti-Bacterial Agent, Lung transplantation, business.industry, lung transplant, liver transplant, infectious, Transplantation, Prospective Studie, liver transplant, Etiology, Postoperative Complication, business, transplantation
Abstract

Infections are a major complication of solid organ transplants (SOTs). This study aimed to describe recipients’ characteristics, and the frequency and etiology of infections and transplant outcome in liver and lung SOTs, and to investigate exposures associated to infection and death in liver transplant recipients. The study population included recipients of SOTs performed in Italy during a 1-year period in ten Italian lung transplant units and eight liver transplant units. Data on comorbidities, infections, retransplantation, and death were prospectively collected using a web-based system, with a 6-month follow-up. The cumulative incidence of infection was 31.7% and 47.8% in liver and lung transplants, respectively, with most infections occurring within the first month after transplantation. Gram-negatives, which were primarily multidrug-resistant, were the most frequent cause of infection. Death rates were 0.42 per 1000 recipient-days in liver transplants and 1.41 per 1000 recipient-days in lung transplants. Infection after SOT in adult liver recipients is associated to an increased risk of death (OR = 13.25; p-value < 0.001). Given the frequency of infection caused by multidrug-resistant microorganisms in SOT recipients in Italy and the heavy impact of infections on the transplant outcome, the reinforcement of surveillance and control activities to prevent the transmission of multidrug-resistant microorganisms in SOT recipients represents a priority. The implementation of the study protocol in liver and lung transplant units and the sharing of results have increased the awareness about the threat due to antimicrobial resistance in the country.

Published
2018

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