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,Giuseppe Menna,Annalisa Tondo,Arne Simon,Francesca Bagnasco,Thomas Lehrnbecher,Marco Sarno,Marie Luckowitsch,Maria Rosaria D’Amico,Roland A Ammann,Mariaclaudia Meli,Sasha Palmert,Lillian Sung,Alessio Mesini,Andreas H Groll,Austin Duong,Yona Traubici,Giovanna Russo,Fabianne Carlesse,Evgeny A Idelevich,G.g Solopova ,María Elena Santolaya De Pablo ,Philipp Agyeman ,Gabrielle M Haeusler

doi:10.3390/antibiotics10030266

Abstract

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.

Highlights

Infections represent important complications in pediatric patients receiving antineoplastic chemotherapy, or allogeneic hematopoietic stem cell transplantation (HSCT)
Multinational retrospective study, we collected 1291 Bloodstream infections (BSI) due to non-common skin contaminants occurring in pediatric patients treated with chemotherapy or allogeneic HSCT to study proportions of resistant strains and risk factors for antibiotic resistance, intensive care unit (ICU) admission, or death
A. baumannii complex (25.0%), the 3rd, 5th, and 9th most frequently reported pathogens, respectively. These proportions of resistant strains are worrisome since they regard the antibiotics generally recommended as monotherapy for empirical treatment of febrile neutropenia in pediatric patients [2,4], with the consequent non-negligible risk of treatment failure

Summary

Introduction

Infections represent important complications in pediatric patients receiving antineoplastic chemotherapy, or allogeneic hematopoietic stem cell transplantation (HSCT). The introduction of empirical antibacterial therapy with the combination of an anti-pseudomonal beta-lactam and an aminoglycoside in febrile neutropenic cancer patients has significantly decreased mortality [1,2]. Following the results of a recent a meta-analysis [3] monotherapy with beta-lactams active against Gram-negatives (including P. aeruginosa) is recommended for the management of febrile neutropenia in pediatric patients with cancer [4]. For institutions where resistance rates in Gram-negative isolates are low. This approach requires careful epidemiologic surveillance and continual re-evaluation of empiric antibiotic regimens in light of evolving institutional microbial resistance patterns [4,5]. Antibiotic resistance is a worldwide problem, geographic and institution-level differences are observed (https://atlas-surveillance.com/#/heatmap/resistance)

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