Antibiotic Resistant Bloodstream Infections in Pediatric Patients Receiving Chemotherapy or Hematopoietic Stem Cell Transplant: Factors Associated with Development of Resistance, Intensive Care Admission and Mortality
Elio Castagnola,
Francesca Bagnasco,
Alessio Mesini,
Philipp K. A. Agyeman,
Roland A. Ammann,
Fabianne Carlesse,
Maria Elena Santolaya de Pablo,
Andreas H. Groll,
Gabrielle M. Haeusler,
Thomas Lehrnbecher,
Arne Simon,
Maria Rosaria D’Amico,
Austin Duong,
Evgeny A. Idelevich,
Marie Luckowitsch,
Mariaclaudia Meli,
Giuseppe Menna,
Sasha Palmert,
Giovanna Russo,
Marco Sarno,
Galina Solopova,
Annalisa Tondo,
Yona Traubici,
Lillian Sung
Affiliations
Elio Castagnola
Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
Francesca Bagnasco
Epidemiology and Biostatistics Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
Alessio Mesini
Infectious Diseases Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
Philipp K. A. Agyeman
Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
Roland A. Ammann
Pediatric Hematology/Oncology, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
Fabianne Carlesse
Pediatric Oncology Institute, GRAACC/Federal University of Sao Paulo, Sao Paulo 04023-062, Brazil
Maria Elena Santolaya de Pablo
Facultad de Medicina, Universidad de Chile, Hospital Dr. Luis Calvo Mackenna, Santiago 7500539, Chile
Andreas H. Groll
Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Paediatric Haematology and Oncology, University Children’s Hospital Muenster, 48149 Muenster, Germany
Gabrielle M. Haeusler
The Paediatric Integrated Cancer Service, Parkville, VIC 3052, Australia
Thomas Lehrnbecher
Division of Pediatric Hematology and Oncology, Hospital for Children and Adolescents, University Hospital, Johann Wolfgang Goethe University, 60323 Frankfurt am Main, Germany
Arne Simon
Pediatric Oncology and Hematology, Children’s Hospital Medical Center, University Clinics, 6642 Homburg, Germany
Maria Rosaria D’Amico
Department Hemato-Oncology, AORN Santobono-Pausilipon, 80129 Napoli, Italy
Austin Duong
Child Health Evaluative Sciences, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning, Toronto, ON M5G 0A4, Canada
Evgeny A. Idelevich
Institute of Medical Microbiology, University Hospital Munster, 48149 Munster, Germany
Marie Luckowitsch
Division of Pediatric Hematology and Oncology, Hospital for Children and Adolescents, University Hospital, Johann Wolfgang Goethe University, 60323 Frankfurt am Main, Germany
Mariaclaudia Meli
Pediatric Hemato-Oncology Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
Giuseppe Menna
Department Hemato-Oncology, AORN Santobono-Pausilipon, 80129 Napoli, Italy
Sasha Palmert
Child Health Evaluative Sciences, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning, Toronto, ON M5G 0A4, Canada
Giovanna Russo
Pediatric Hemato-Oncology Unit, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
Marco Sarno
Pediatric Unit, Santa Maria Delle Grazie Hospital, ASL Napoli 2 Nord, Pozzuoli, 80027 Napoli, Italy
Galina Solopova
Dmitry Rogachev Federal Scientific-Clinical Center of Children’s Hematology, Oncology and Immunology, 117997 Moscow, Russia
Annalisa Tondo
Paediatric Haematology/Oncology Department, Meyer Children’s University Hospital, 50134 Florence, Italy
Yona Traubici
Child Health Evaluative Sciences, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning, Toronto, ON M5G 0A4, Canada
Lillian Sung
Child Health Evaluative Sciences, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning, Toronto, ON M5G 0A4, Canada
Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of S. aureus and vancomycin resistance in 40% of E. faecium. Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant S. aureus was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to >3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs.
