Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia After Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey
Authors: 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 , Scimè Rosanna , Musso Maurizio , Cudillo Laura , Sica Simona , 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 ,   Gruppo Italiano Trapianto di Midollo Osseo (GITMO) and Associazione Microbiologi Clinici Italiani (AMCLI), 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 , Baldi Maria Teresa , Cudillo L , Picardi Alessandra , Arcese William , Fontana Carla , Sica S , Giammarco Sabrina , Spanu Teresa , Castagna L , Crocchiolo Roberto , Casari Erminia , Corradini Paolo , 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 , Marone Piero , Pisapia Giovanni , Palazzo Giulia , 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 , Cambò 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 , Ravizzola Giuseppe , 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 
Published: August 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.