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

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; 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

doi:10.1093/cid/cix646

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

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 RasconIsabel 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

Department of Clinical Medicine

75 Citations (Scopus)

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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.

Original language	English
Journal	Clinical Infectious Diseases
Volume	65
Issue number	11
Pages (from-to)	1819-1828
ISSN	1058-4838
DOIs	https://doi.org/10.1093/cid/cix646
Publication status	Published - 1 Dec 2017

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Averbuch, D., Tridello, G., Hoek, J., Mikulska, M., Akan, H., Yanez San Segundo, L., Pabst, T., Özçelik, T., Klyasova, G., Donnini, I., Wu, D., Gülbas, Z., Zuckerman, T., Botelho de Sousa, A., Beguin, Y., Xhaard, A., Bachy, E., Ljungman, P., de la Camara, R., ... Cesaro, S. (2017). 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. Clinical Infectious Diseases, 65(11), 1819-1828. https://doi.org/10.1093/cid/cix646

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. / Averbuch, Diana; Tridello, Gloria; Hoek, Jennifer et al.
In: Clinical Infectious Diseases, Vol. 65, No. 11, 01.12.2017, p. 1819-1828.

Research output: Contribution to journal › Journal article › Research › peer-review

Averbuch, D, Tridello, G, Hoek, J, Mikulska, M, Akan, H, Yanez San Segundo, L, Pabst, T, Özçelik, T, Klyasova, G, Donnini, I, Wu, D, Gülbas, Z, Zuckerman, T, Botelho de Sousa, A, Beguin, Y, Xhaard, A, Bachy, E, Ljungman, P, de la Camara, R, Rascon, J, Ruiz Camps, I, Vitek, A, Patriarca, F, Cudillo, L, Vrhovac, R, Shaw, PJ, Wolfs, T, O'Brien, T, Avni, B, Silling, G, Al Sabty, F, Graphakos, S, Sankelo, M, Sengeloev, H, Pillai, S, Matthes, S, Melanthiou, F, Iacobelli, S, Styczynski, J, Engelhard, D & Cesaro, S 2017, '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', Clinical Infectious Diseases, vol. 65, no. 11, pp. 1819-1828. https://doi.org/10.1093/cid/cix646

Averbuch D, Tridello G, Hoek J, Mikulska M, Akan H, Yanez San Segundo L et al. 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. Clinical Infectious Diseases. 2017 Dec 1;65(11):1819-1828. doi: 10.1093/cid/cix646

Averbuch, Diana ; Tridello, Gloria ; Hoek, Jennifer et al. / 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. In: Clinical Infectious Diseases. 2017 ; Vol. 65, No. 11. pp. 1819-1828.

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title = "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",

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.",

author = "Diana Averbuch and Gloria Tridello and Jennifer Hoek and Malgorzata Mikulska and Hamdi Akan and {Yanez San Segundo}, Lucrecia and Thomas Pabst and T{\"u}lay {\"O}z{\c c}elik and Galina Klyasova and Irene Donnini and Depei Wu and Zafer G{\"u}lbas and Tsila Zuckerman and {Botelho de Sousa}, Aida and Yves Beguin and Ali{\'e}nor Xhaard and Emmanuel Bachy and Per Ljungman and {de la Camara}, Rafael and Jelena Rascon and {Ruiz Camps}, Isabel and Antonin Vitek and Francesca Patriarca and Laura Cudillo and Radovan Vrhovac and Shaw, {Peter J} and Tom Wolfs and Tracey O'Brien and Batia Avni and Gerda Silling and {Al Sabty}, Firas and Stelios Graphakos and Marja Sankelo and Henrik Sengeloev and Srinivas Pillai and Susanne Matthes and Frederiki Melanthiou and Simona Iacobelli and Jan Styczynski and Dan Engelhard and Simone Cesaro",

year = "2017",

month = dec,

day = "1",

doi = "10.1093/cid/cix646",

language = "English",

volume = "65",

pages = "1819--1828",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "11",

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TY - JOUR

T1 - Antimicrobial Resistance in Gram-Negative Rods Causing Bacteremia in Hematopoietic Stem Cell Transplant Recipients

T2 - Intercontinental Prospective Study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group

AU - Averbuch, Diana

AU - Tridello, Gloria

AU - Hoek, Jennifer

AU - Mikulska, Malgorzata

AU - Akan, Hamdi

AU - Yanez San Segundo, Lucrecia

AU - Pabst, Thomas

AU - Özçelik, Tülay

AU - Klyasova, Galina

AU - Donnini, Irene

AU - Wu, Depei

AU - Gülbas, Zafer

AU - Zuckerman, Tsila

AU - Botelho de Sousa, Aida

AU - Beguin, Yves

AU - Xhaard, Aliénor

AU - Bachy, Emmanuel

AU - Ljungman, Per

AU - de la Camara, Rafael

AU - Rascon, Jelena

AU - Ruiz Camps, Isabel

AU - Vitek, Antonin

AU - Patriarca, Francesca

AU - Cudillo, Laura

AU - Vrhovac, Radovan

AU - Shaw, Peter J

AU - Wolfs, Tom

AU - O'Brien, Tracey

AU - Avni, Batia

AU - Silling, Gerda

AU - Al Sabty, Firas

AU - Graphakos, Stelios

AU - Sankelo, Marja

AU - Sengeloev, Henrik

AU - Pillai, Srinivas

AU - Matthes, Susanne

AU - Melanthiou, Frederiki

AU - Iacobelli, Simona

AU - Styczynski, Jan

AU - Engelhard, Dan

AU - Cesaro, Simone

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

U2 - 10.1093/cid/cix646

DO - 10.1093/cid/cix646

M3 - Journal article

C2 - 29020364

SN - 1058-4838

VL - 65

SP - 1819

EP - 1828

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 11

ER -