Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in Hematopoietic Stem Cell Transplant Recipients: Intercontinental Prospective Study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group

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Diana Averbuch, Gloria Tridello, Jennifer Hoek, Malgorzata Mikulska, Hamdi Akan, Lucrecia Yanez San Segundo, Thomas Pabst, Tülay Özçelik, Galina Klyasova, Irene Donnini, Depei Wu, Zafer Gülbas, Tsila Zuckerman, Aida Botelho de Sousa, Yves Beguin, Aliénor Xhaard, Emmanuel Bachy, Per Ljungman, Rafael de la Camara, Jelena Rascon & 21 andre Isabel Ruiz Camps, Antonin Vitek, Francesca Patriarca, Laura Cudillo, Radovan Vrhovac, Peter J Shaw, Tom Wolfs, Tracey O'Brien, Batia Avni, Gerda Silling, Firas Al Sabty, Stelios Graphakos, Marja Sankelo, Henrik Sengeloev, Srinivas Pillai, Susanne Matthes, Frederiki Melanthiou, Simona Iacobelli, Jan Styczynski, Dan Engelhard, Simone Cesaro

Background: This intercontinental study aimed to study gram-negative rod (GNR) resistance in hematopoietic stem cell transplantation (HSCT).

Methods: GNR bacteremias occurring during 6 months post-HSCT (February 2014-May 2015) were prospectively collected, and analyzed for rates and risk factors for resistance to fluoroquinolones, noncarbapenem anti-Pseudomonas β-lactams (noncarbapenems), carbapenems, and multidrug resistance.

Results: Sixty-five HSCT centers from 25 countries in Europe, Australia, and Asia reported data on 655 GNR episodes and 704 pathogens in 591 patients (Enterobacteriaceae, 73%; nonfermentative rods, 24%; and 3% others). Half of GNRs were fluoroquinolone and noncarbapenem resistant; 18.5% carbapenem resistant; 35.2% multidrug resistant. The total resistance rates were higher in allogeneic HSCT (allo-HSCT) vs autologous HSCT (auto-HSCT) patients (P < .001) but similar in community-acquired infections. Noncarbapenem resistance and multidrug resistance were higher in auto-HSCT patients in centers providing vs not providing fluoroquinolone prophylaxis (P < .01). Resistance rates were higher in southeast vs northwest Europe and similar in children and adults, excluding higher fluoroquinolone- and β-lactam/β-lactamase inhibitor resistance rates in allo-HSCT adults. Non-Klebsiella Enterobacteriaceae were rarely carbapenem resistant. Multivariable analysis revealed resistance risk factors in allo-HSCT patients: fluoroquinolone resistance: adult, prolonged neutropenia, breakthrough on fluoroquinolones; noncarbapenem resistance: hospital-acquired infection, breakthrough on noncarbapenems or other antibiotics (excluding fluoroquinolones, noncarbapenems, carbapenems), donor type; carbapenem resistance: breakthrough on carbapenem, longer hospitalization, intensive care unit, previous other antibiotic therapy; multidrug resistance: longer hospitalization, breakthrough on β-lactam/β-lactamase inhibitors, and carbapenems. Inappropriate empiric therapy and mortality were significantly more common in infections caused by resistant bacteria.

Conclusions: Our data question the recommendation for fluoroquinolone prophylaxis and call for reassessment of local empiric antibiotic protocols. Knowledge of pathogen-specific resistance enables early appropriate empiric therapy. Monitoring of resistance is crucial.

Clinical Trials Registration: NCT02257931.

TidsskriftClinical Infectious Diseases
Udgave nummer11
Sider (fra-til)1819-1828
StatusUdgivet - 2017

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