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 Yaňez 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 others 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

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 languageEnglish
Pages (from-to)1819-1828
Number of pages10
JournalClinical Infectious Diseases
Volume65
Issue number11
DOIs
Publication statusPublished - Dec 1 2017

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Fluoroquinolones
Carbapenems
Bacteremia
Hematopoietic Stem Cells
Bone Marrow Transplantation
Communicable Diseases
Prospective Studies
Hematopoietic Stem Cell Transplantation
Transplants
Lactams
Multiple Drug Resistance
Enterobacteriaceae
Anti-Bacterial Agents
Hospitalization
Community-Acquired Infections
Transplant Recipients
R Factors
Cross Infection
Pseudomonas
Neutropenia

Keywords

  • antimicrobial resistance
  • bacteremia
  • gram-negative rods
  • hematopoietic stem cell transplantation

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

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; Mikulska, Malgorzata; Akan, Hamdi; Yaňez 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.

In: Clinical Infectious Diseases, Vol. 65, No. 11, 01.12.2017, p. 1819-1828.

Research output: Contribution to journalArticle

Averbuch, D, Tridello, G, Hoek, J, Mikulska, M, Akan, H, Yaňez 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, Diana ; Tridello, Gloria ; Hoek, Jennifer ; Mikulska, Malgorzata ; Akan, Hamdi ; Yaňez 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. / 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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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.",
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author = "Diana Averbuch and Gloria Tridello and Jennifer Hoek and Malgorzata Mikulska and Hamdi Akan and {Yaňez San Segundo}, Lucrecia and Thomas Pabst and T{\"u}lay {\"O}z{\cc}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",
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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 - Yaňez 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.

KW - antimicrobial resistance

KW - bacteremia

KW - gram-negative rods

KW - hematopoietic stem cell transplantation

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