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