Diana Averbuch1, Gloria Tridello2, Jennifer Hoek3, Malgorzata Mikulska4, Hamdi Akan5, Lucrecia Yanez San Segundo6, Thomas Pabst7, Tülay Özçelik8, Galina Klyasova9, Irene Donnini10, Depei Wu11, Zafer Gülbas12, Tsila Zuckerman13, Aida Botelho de Sousa14, Yves Beguin15, Aliénor Xhaard16, Emmanuel Bachy17, Per Ljungman18, Rafael de la Camara19, Jelena Rascon20, Isabel Ruiz Camps21, Antonin Vitek22, Francesca Patriarca23, Laura Cudillo24, Radovan Vrhovac25, Peter J Shaw26, Tom Wolfs27, Tracey O'Brien28, Batia Avni1, Gerda Silling29, Firas Al Sabty30, Stelios Graphakos31, Marja Sankelo32, Henrik Sengeloev33, Srinivas Pillai34, Susanne Matthes35, Frederiki Melanthiou36, Simona Iacobelli24, Jan Styczynski37, Dan Engelhard1, Simone Cesaro2. 1. Hadassah University Hospital, Jerusalem, Israel. 2. Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. 3. European Bone Marrow Transplantation Data Office, Leiden, The Netherlands. 4. Ospedale San Martino, Genova, Italy. 5. Faculty of Medicine, Ankara University, Turkey. 6. Hospital Universitario Marqués de Valdecilla, Santander, Spain. 7. University Hospital, Bern, Switzerland. 8. Florence Nightingale Sisli Hospital, Istanbul, Turkey. 9. National Research Center for Hematology, Moscow, Russia. 10. Azienda Ospedaliera Universitaria Careggi, Firenze, Italy. 11. First Affiliated Hospital of Soochow University, Suzhou Jiangsu, China. 12. Anadolu Medical Center Hospital, Kocaeli, Turkey. 13. Rambam Medical Center, Haifa, Israel. 14. Hospital dos Capuchos, Lisbon, Portugal. 15. University of Liege, Belgium. 16. Hospital St Louis, Paris, France. 17. Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, France. 18. Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden. 19. Hospital de la Princesa, Madrid, Spain. 20. University Hospital Santariskiu Klinikos, Vilnius, Lithuania. 21. Hospital Vall d'Hebron, Barcelona, Spain. 22. Institute of Hematology and Blood Transfusion, Prague, Czech Republic. 23. Azienda Ospedaliero Universitaria, Udine, Italy. 24. Tor Vergata University, Rome, Italy. 25. University Hospital Center Rebro, Zagreb, Croatia. 26. The Children's Hospital at Westmead, Sydney, Australia. 27. University Hospital for Children, Utrecht, The Netherlands. 28. Sydney Children's Hospital, Randwick, Australia. 29. University of Münster, Germany. 30. University Hospital, Bratislava, Slovakia. 31. St Sophia Children's Hospital, Athens, Greece. 32. Tampere University Hospital, Finland. 33. Rigshospitalet, Copenhagen, Denmark. 34. University Hospital of North Staffordshire, Stoke, United Kingdom. 35. St Anna Kinderspital, Vienna, Austria. 36. Nicosia General Hospital, Nicosia Strovolos, Cyprus. 37. Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland.
Abstract
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.
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.
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