Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Antibiotic prophylaxis and management of infections in pediatric hematopoietic stem cell transplantation: a survey from the Stem Cell Transplant and the Infectious Disease Working Groups of the AIEOP network

Bone Marrow Transplantation volume 57, pages 1851–1853 (2022)Cite this article

Subjects

Infectious complications are a major concern for children undergoing hematopoietic stem cell transplantation (HSCT), representing a leading cause of morbidity and mortality [1]. Antibacterial prophylaxis is a preventive strategy, largely used in the adult HSCT setting [2]; however, recent evidence questioned the effect on the risk of mortality, emergence of multidrug resistance germs, and bloodstream infections (BSI) thus challenging its role [3]. In the recent 8th European Conference on Infections in Leukaemia (ECIL-8) prophylaxis is not routinary recommended for pediatric patients with neutropenia during the pre-engraftment phase of HSCT, reserving this option in individual patients after a careful risk–benefit evaluation [4]. Regarding initial empirical antibacterial therapy, the ECIL-8 guidelines recommend monotherapy with an antipseudomonal non-carbapenem beta-lactam and beta-lactamase inhibitor or with fourth-generation cephalosporin in clinically stable patients, while a carbapenem with or without a second agent is reserved for clinically unstable patients [4]. An appropriate antibacterial management is also critical to prevent the risk of emergence of multidrug resistant (MDR) strains, particularly from Gram-negative bacteria, that are associated with increased infection-related mortality [5]. Recently, increasing evidence has emerged about antimicrobial stewardship programs (ASP) in pediatric cancer patients as effective measures to reduce antibiotic use and to improve outcomes [6]. Gut colonization screening and local epidemiological monitoring could also help to identify MDR strains, representing an useful strategy in guiding prophylaxis and empiric therapy strategy [7]. While evidence and recommendations on the management of infections are growing, the adherence of pediatric HSCT centers remains unknown. A previous survey from the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) described a significant variability in prophylaxis and management of febrile neutropenia in pediatric cancer patients across Italian centers. In HSCT setting, 78% of Italian centers performed antibacterial prophylaxis in both autologous and allogenic recipients while combination therapy was used in 55% of autologous and 67% of allogenic transplanted patients [8]. A similar variability in prophylactic measures was recently demonstrated in Blood and Marrow Transplant Clinical Trials Network centers and among pediatric acute myeloid leukemia patients in the International Berlin–Frankfurt–Munster study group [9, 10].

To investigate the real-life approach to anti-infective management in pediatric patients (<18 years) undergoing autologous or allogenic HSCT in Italy, we conducted a nation-wide survey among AIEOP centers. The first outcome was the assessment of antibacterial prophylaxis measures, and the secondary included current empiric antibiotic management in neutropenic fever, colonization screening measures and presence of ASP. On January 11, 2022 an 18-items web-based questionnaire was distributed to all 21 AIEOP centers performing HSCT (Supplementary file).

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Data availability

The single answers from each participating center are available from the corresponding author on reasonable request.

References

  1. Dandoy CE, Ardura MI, Papanicolaou GA, Auletta JJ. Bacterial bloodstream infections in the allogeneic hematopoietic cell transplant patient: new considerations for a persistent nemesis. Bone Marrow Transpl. 2017;52:1091–106.

    Article  CAS  Google Scholar 

  2. Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, et al. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Engl J Med. 2005;353:977–87.

    Article  CAS  PubMed  Google Scholar 

  3. Alexander S, Fisher BBTB, Gaur AH, Dvorak CC, Villa Luna D, Dang H, et al. Effect of levofloxacin prophylaxis on bacteremia in children with acute Leukemia or undergoing hematopoietic stem cell transplantation a randomized clinical trial. JAMA. 2018;320:995–1004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lehrnbecher T, Averbuch D, Castagnola E, Cesaro S, Ammann RA, Garcia-Vidal C, et al. 8th European Conference on Infections in Leukaemia: 2020 guidelines for the use of antibiotics in paediatric patients with cancer or post-haematopoietic cell transplantation. Lancet Oncol. 2021. https://doi.org/10.1016/s1470-2045(20)30725-7.

  5. Averbuch D, Tridello G, Hoek J, Mikulska M, Akan H, Yaňez 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. Clin Infect Dis. 2017;65:1819–28.

    Article  CAS  PubMed  Google Scholar 

  6. Muratore E, Baccelli F, Leardini D, Campoli C, Belotti T, Viale P, et al. Antimicrobial Stewardship Interventions in Pediatric Oncology: A Systematic Review. J Clin Med. 2022;11:4545.

  7. Sadowska-Klasa A, Piekarska A, Prejzner W, Bieniaszewska M, Hellmann A. Colonization with multidrug-resistant bacteria increases the risk of complications and a fatal outcome after allogeneic hematopoietic cell transplantation. Ann Hematol. 2018;97:509–17.

    Article  CAS  PubMed  Google Scholar 

  8. Livadiotti S, Milano GM, Serra A, Folgori L, Jenkner A, Castagnola E, et al. A survey on hematology-oncology pediatric AIEOP centers: prophylaxis, empirical therapy and nursing prevention procedures of infectious complications. Haematologica. 2012;97:147–50.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Rashidi A, Wangjam T, Bhatt AS, Weisdorf DJ, Holtan SG. Antibiotic practice patterns in hematopoietic cell transplantation: a survey of blood and marrow transplant clinical trials network centers. Am J Hematol. 2018;93:E348–50.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Klein K, Hasle H, Abrahamsson J, De Moerloose B, Kaspers GJL. Differences in infection prophylaxis measures between paediatric acute myeloid leukaemia study groups within the international Berlin–Frankfürt–Münster (I-BFM) study group. Br J Haematol. 2018;183:87–95.

    Article  PubMed  Google Scholar 

  11. Lehrnbecher T, Fisher BT, Phillips B, Alexander S, Ammann RA, Beauchemin M, et al. Guideline for antibacterial prophylaxis administration in pediatric cancer and hematopoietic stem cell transplantation. Clin Infect Dis. 2020;71:226–36.

    Article  CAS  PubMed  Google Scholar 

  12. Dhanya R, Agarwal RK, Ramprakash S, Trivedi D, Shah V, Bhat N, et al. Do weekly surveillance cultures contribute to antibiotic stewardship and correlate with outcome of HSCT in children? A multicenter real-world experience of 5 years from the Indian subcontinent. Transpl Cell Ther. 2022;000:1–7.

    Google Scholar 

  13. Pession A, Zama D, Muratore E, Leardini D, Gori D, Guaraldi F, et al. Fecal microbiota transplantation in allogeneic hematopoietic stem cell transplantation recipients: a systematic review. J Pers Med. 2021;11. https://doi.org/10.3390/jpm11020100.

  14. Wolf J, Sun Y, Tang L, Newland JG, Gerber JS, Van Dyke CJ, et al. Antimicrobial stewardship barriers and goals in pediatric oncology and bone marrow transplantation: a survey of antimicrobial stewardship practitioners. Infect Control Hosp Epidemiol. 2015;37:343–7.

Download references

Author information

Author notes

  1. These authors contributed equally: Daniele Zama, Riccardo Masetti.

  2. These authors contributed equally: Daria Pagliara, Simone Cesaro.

Authors and Affiliations

  1. Pediatric Emergency Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

    Daniele Zama

  2. Pediatric Oncology and Hematology “Lalla Seràgnoli”, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

    Riccardo Masetti, Francesco Baccelli, Davide Leardini, Edoardo Muratore, Nicoletta Abram & Arcangelo Prete

  3. Clinica Pediatrica Università degli Studi di Milano Bicocca, Fondazione MBBM, Monza, Italy

    Francesca Vendemini

  4. Pediatric Hematology, Oncology and Stem Cell Transplant Center, Department of Woman’s and Child’s Health, University of Padua, Padua, Italy

    Alessandra Biffi

  5. Department of Pediatric and Gynecology, Pediatric Onco-Hematology, Perugia Regional Hospital, Perugia, Italy

    Katia Perruccio

  6. Department of Pediatric Hemato-Oncology, AORN Santobono-Pausilipon, Naples, Italy

    Maria Rosaria D’Amico

  7. Department of Pediatric Hemato-Oncology, HSCT Unit, IRCCS, Istituto Giannina Gaslini, Genova, Italy

    Maura Faraci

  8. Department of Pediatric Hematology/Oncology and Hematopoietic Stem Cell Transplantation, Meyer Children’s University Hospital, Florence, Italy

    Veronica Tintori

  9. Department of Pediatrics, Hemato-Oncology Unit, ‘Casa Sollievo della Sofferenza’ Hospital, San Giovanni Rotondo, Italy

    Anita Spirito

  10. Centro di Riferimento Regionale di Ematologia ed Oncologia Pediatrica, Azienda Policlinico “G. Rodolico - San Marco”, Catania, Italy

    Luca Lo Nigro

  11. Department of Pediatric Hematology and Oncology, Bambino Gesù Children’s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy

    Franco Locatelli & Daria Pagliara

  12. Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Roberto Luksch

  13. Pediatric Oncohematology, Stem Cell Transplantation and Cell Therapy Division, A.O.U. Città della Salute e della Scienza-Regina Margherita Children’s Hospital, Turin, Italy

    Francesco Saglio

  14. UOC Pediatria Oncoematologica, AOUC Policlinico Bari, Bari, Italy

    Nicola Santoro

  15. Pediatric Oncohematology and Bone Marrow Transplant Unit, Children’s Hospital, Spedali Civili, Brescia, Italy

    Elena Soncini

  16. Department of Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Marco Zecca

  17. Department of Pediatric Hemato-Oncology, ARNAS Ospedali Civico, G. Di Cristina, Palermo, Italy

    Ottavio Ziino

  18. Pediatric Hematology Oncology Unit, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy

    Simone Cesaro

Authors
  1. Daniele Zama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Riccardo Masetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francesco Baccelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Davide Leardini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Edoardo Muratore
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nicoletta Abram
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Francesca Vendemini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alessandra Biffi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Katia Perruccio
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Maria Rosaria D’Amico
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Maura Faraci
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Veronica Tintori
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Anita Spirito
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Luca Lo Nigro
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Franco Locatelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Roberto Luksch
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Francesco Saglio
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Nicola Santoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Elena Soncini
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Marco Zecca
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Ottavio Ziino
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Arcangelo Prete
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Daria Pagliara
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Simone Cesaro
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DZ, RM and DL designed the study; FB, EM, NA and DL prepared the survey; DZ, SC and DP were responsible for the collection of clinical data from the working groups; FV, AB, KP, MRD, MF, VT, AS, LLN, FL, RL, FS, NS, ES, MZ, OZ and AP provided centers’ information; DL and FB wrote the manuscript; DZ, RM, EM, DP and SC critically reviewed the manuscript.

Corresponding author

Correspondence to Davide Leardini.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zama, D., Masetti, R., Baccelli, F. et al. Antibiotic prophylaxis and management of infections in pediatric hematopoietic stem cell transplantation: a survey from the Stem Cell Transplant and the Infectious Disease Working Groups of the AIEOP network. Bone Marrow Transplant 57, 1851–1853 (2022). https://doi.org/10.1038/s41409-022-01793-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-022-01793-5

This article is cited by

Search

Advanced search

Quick links