Background Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. Methods We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. Results The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45-3.13; P <.001) and auto-HSCT (2.43; 1.22-4.84; P =.01). Conclusions Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. Clinical Trials registration NCT02088840.

Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia after Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey

MUSSO, Maurizio;Sica, Simona;Corradini, Paolo;MARCHESI, Francesco;Amico, Lucia;Bruno, Benedetto;Costa, Cristina;MARCHESE, ANNA;Milone, G.;LEOTTA, Salvatore;FONTANA, ELISA CARLA;Sica, S.;Greco, Raffaella;PALAZZO, GIULIA;Vacca, Adriana;SANNA, MARCO;Cilloni, Daniela;De Gobbi, Marco;Fagioli, Franca;Carraro, Francesca;BORGHERO, Carlo;CARAVELLI, DANIELA;GALLO, Susanna;
2017

Abstract

Background Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. Methods We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. Results The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45-3.13; P <.001) and auto-HSCT (2.43; 1.22-4.84; P =.01). Conclusions Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. Clinical Trials registration NCT02088840.
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epidemiology; Gram negative bacteremia; multidrug resistance; stem cell transplant; survival; Microbiology (medical); Infectious Diseases
Girmenia, Corrado; Bertaina, Alice; Piciocchi, Alfonso; Perruccio, Katia; Algarotti, Alessandra; Busca, Alessandro; Cattaneo, Chiara; Raiola, Anna Maria; Guidi, Stefano; Iori, Anna Paola; Candoni, Anna; Irrera, Giuseppe; Milone, Giuseppe; Marcacci, Giampaolo; Scimã, Rosanna; Musso, Maurizio; Cudillo, Laura; Simona, Sica; Castagna, Luca; Corradini, Paolo; Marchesi, Francesco; Pastore, Domenico; Alessandrino, Emilio Paolo; Annaloro, Claudio; Ciceri, Fabio; Santarone, Stella; Nassi, Luca; Farina, Claudio; Viscoli, Claudio; Rossolini, Gian Maria; Bonifazi, Francesca; Rambaldi, Alessandro; Capria, Saveria; Bertaina, A.; Mastronuzzi, Angela; Pagliara, Daria; Bernaschi, Paola; Amico, Lucia; Carotti, Alessandra; Mencacci, Antonella; Busca, A.; Bruno, Benedetto; Costa, Cristina; Passi, Angela; Ravizzola, Giuseppe; Angelucci, Emanuele; Marchese, Anna; Pecile, Patrizia; Candoni, A.; Ventura, Giovanna; Fanin, Renato; Scarparo, Claudio; Barbaro, Angelo; Milone, G.; Leotta, Salvatore; Marchese, Anna Elisa; Marcacci, G.; Becchimanzi, Cristina; Donnarumma, Daniela; Tringali, Stefania; Baldi, Maria Teresa; Scalone, Renato; Cudillo, L.; Picardi, Alessandra; Arcese, William; Carla, Fontana; Sica, S.; Giammarco, Sabrina; Spanu, Teresa; Castagna, L.; Crocchiolo, Roberto; Casari, Erminia; Mussetti, Alberto; Conte, Eutilia; Ensoli, Fabrizio; Miragliotta, Giuseppe; Marone, Piero; Arghittu, Milena; Greco, Raffaella; Forcina, Alessandra; Chichero, Paola; Santarone, S.; Di Bartolomeo, Paolo; Fazii, Paolo; Kroumova, Vesselina; Decembrino, Nunzia; Zecca, Marco; Pisapia, Giovanni; Palazzo, Giulia; Lanino, Edoardo; Faraci, Maura; Castagnola, Elio; Bandettini, Roberto; Pastano, Rocco; Sammassimo, Simona; Passerini, Rita; Stefani, Piero Maria; Gherlinzoni, Filippo; Rigoli, Roberto; Prezioso, Lucia; Cambã², Benedetta; Calderaro, Adriana; Carella, Angelo Michele; Cascavilla, Nicola; Labonia, Maria Teresa; Celeghini, Ivana; Mordini, Nicola; Piana, Federica; Vacca, Adriana; Sanna, Marco; Podda, Giovanni; Corsetti, Maria Teresa; Rocchetti, Andrea; Cilloni, Daniela; De Gobbi, Marco; Bianco, Ornella; Fagioli, Franca; Carraro, Francesca; De Intinis, Gianfranco; Severino, Alessandro; Proia, Anna; Parisi, Gabriella; Vallisa, Daniele; Confalonieri, Massimo; Russo, Domenico; Malagola, Michele; Galieni, Piero; Falcioni, Sadia; Travaglini, Valeria; Raimondi, Roberto; Borghero, Carlo; Pavan, Giacomina; Prete, Arcangelo; Belotti, Tamara; Ambretti, Simone; Imola, Manuela; Mianulli, Anna Maria; Pedna, Maria Federica; Cesaro, Simone; Lo Cascio, Giuliana; Ferrari, Antonella; Piedimonte, Monica; Santino, Iolanda; Calandrelli, Monica; Olivieri, Attilio; Orecchioni, Francesca; Mirabile, Milena; Centurioni, Riccardo; Gironacci, Luciana; Caravelli, Daniela; Gallo, Susanna; De Filippi, Marco; Cupelli, Luca; Dentamaro, Teresa; Falco, Silvana; Eugenio, Ospedale S; Marotta, Serena; Risitano, Antonio; Lula, Dora; Musto, Pellegrino; Pietrantuono, Giuseppe; Traficante, Antonio; Cerchiara, Elisabetta; Tirindelli, Maria Cristina; Dicuonzo, Giordano; Chierichini, Anna; Anaclerico, Barbara; Placanica, Paola
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