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

Simona Sica, Giulio Ventura, Cecilia Alejandra Fontana, Teresa Spanu, Marco Confalonieri, Luigi Castagna, Brunella Bruno, Alessandra Maria Marchese, Salvatore Nuccio Leotta, Eliana Conte, Giovanni Pisapia, Maria Maddalena Sanna, Anna Silvia Proia, Maria Rosa Raimondi, Giuseppe Pavan, Alessandra Olivieri, Corrado Girmenia, Alice Bertaina, Alfonso Piciocchi, Katia PerruccioAlessandra Algarotti, Alessandro Busca, Chiara Cattaneo, Anna Maria Raiola, Stefano Guidi, Anna Paola Iori, Anna Candoni, Giuseppe Irrera, Giuseppe Milone, Giampaolo Marcacci, Rosanna Scimè, Maurizio Musso, Luca Castagna, Paolo Corradini, Francesco Marchesi, Domenico Pastore, Emilio Paolo Alessandrino, Claudio Annaloro, Fabio Ciceri, Stella Santarone, Luca Nassi, Claudio Farina, Claudio Viscoli, Gian Maria Rossolini, Francesca Bonifazi, Alessandro Rambaldi

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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.
Original languageEnglish
Pages (from-to)1884-1896
Number of pages13
JournalClinical Infectious Diseases
Publication statusPublished - 2017


  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Bacteremia
  • Child
  • Child, Preschool
  • Drug Resistance, Multiple, Bacterial
  • Escherichia coli
  • Female
  • Gram negative bacteremia
  • Gram-Negative Bacteria
  • Gram-Negative Bacterial Infections
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Incidence
  • Infant
  • Italy
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Transplantation Conditioning
  • Transplantation, Autologous
  • Transplantation, Homologous
  • Young Adult
  • epidemiology
  • multidrug resistance
  • stem cell transplant
  • survival


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