Skip to main content

Advertisement

SpringerLink
Log in

Antibiotic prophylaxis in children with cancer or who have undergone hematopoietic cell transplantation

  • Review
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Bacterial infections are common in children with cancer and can lead to life-threatening complications. Infections in these patients mainly occur during neutropenic periods, and may be caused by Gram-positive or Gram-negative bacteria. The patients at highest risk of serious infections include those with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML), and those undergoing myeloablative hematopoietic cell transplantation (HCT). This is a review with the main aim of making a critical appraisal of the literature, and summarising what is currently known and can be recommended. The most significant studies support the use of floroquinolones (mainly ciprofloxacin) as the most rational approach to treat pediatric patients with probably long-lasting neutropenia, although trimetoprim-sulphametoxazole and amoxicillin/clavulanate may theoretically be valid alternatives. No prophylaxis seems to be needed for children with cancer without severe neutropenia. However, a global evaluation of the studies of antibiotic prophylaxis in children with cancer indicates that there are not enough data to prepare definite guidelines for its use or avoidance in pediatric oncology, and so further studies are needed. It is not only important to define the best antibiotic regimens for the children in whom such prophylaxis is useful, but also to identify precisely those who do not need it. This would avoid the antibiotic misuse that probably occurs at the moment because many low-risk children with cancer are treated. As prophylaxis against infections requires long-term adherence to an antibiotic regimen, the attitudes and beliefs of stakeholders need to be fully considered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Sung L, Lange BJ, Gerbing RB, Alonzo TA, Feusner J (2007) Microbiologically documented infections and infection-related mortality in children with acute myeloid leukemia. Blood 110:3532–3539

    Article  CAS  PubMed  Google Scholar 

  2. Vento S, Cainelli F (2003) Infections in patients with cancer undergoing chemotherapy: aetiology, prevention, and treatment. Lancet Oncol 4:595–604

    Article  PubMed  Google Scholar 

  3. Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, Feld R, Pizzo PA, Rolston KV, Shenep JL, Young LS (2002) 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 34:730–751

    Article  PubMed  Google Scholar 

  4. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JAH, Wingard JR (2011) Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 52:e56–e93

    Article  PubMed  Google Scholar 

  5. Phillips R, Hancock B, Graham J, Bromham N, Jin H, Berendse S (2012) Prevention and management of neutropenic sepsis in patients with cancer: summary of NICE guidance. BMJ 345:e5368

    Article  PubMed  Google Scholar 

  6. Lehrnbecher T, Ethier MC, Zaoutis T, Creutzig U, Gamis A, Reinhardt D, Aplenc R, Sung L (2009) International variations in infection supportive care practices for paediatric patients with acute myeloid leukaemia. Br J Haematol 147:125–128

    Article  PubMed  Google Scholar 

  7. Livadiotti S, Milano GM, Serra A, Folgori L, Jenkner A, Castagnola E, Cesaro S, Rossi MR, Barone A, Zanazzo G, Nesi F, Licciardello M, De Santis R, Ziino O, Cellini M, Porta F, Caselli D, Pontrelli G, Infectious Diseases Working Group of the Associazione Italiana Ematologia Oncologia Pediatrica (2012) A survey on hematology-oncology pediatric AIEOP centers: prophylaxis, empirical therapy and nursing prevention procedures of infectious complications. Haematologica 97:147–150

    Article  PubMed  Google Scholar 

  8. Castagnola E, Fontana V, Caviglia I, Caruso S, Faraci M, Fioredda F, Garrè ML, Moroni C, Conte M, Losurdo G, Scuderi F, Bandettini R, Tomà P, Viscoli C, Haupt R (2007) A prospective study on the epidemiology of febrile episodes during chemotherapy-induced neutropenia in children with cancer or after hemopoietic stem cell transplantation. Clin Infect Dis 45:1296–1304

    Article  PubMed  Google Scholar 

  9. Wicki S, Keisker A, Aebi C, Leibundgut K, Hirt A, Ammann RA (2008) Risk prediction of fever in neutropenia in children with cancer: a step towards individually tailored supportive therapy? Pediatr Blood Cancer 51:778–783

    Article  PubMed  Google Scholar 

  10. Bagnasco F, Haupt R, Fontana V, Valsecchi MG, Rebora P, Caviglia I, Caruso S, Castagnola E (2012) Risk of repeated febrile episodes during chemotherapy-induced granulocytopenia in children with cancer: a prospective single center study. J Chemother 24:155–160

    Article  PubMed  Google Scholar 

  11. Ariffin H, Navaratnam P, Lin HP (2002) Surveillance study of bacteraemic episodes in febrile neutropenic children. Int J Clin Pract 56:237–240

    CAS  PubMed  Google Scholar 

  12. Schimpff SC, Young V, Green E, Vermeulen GD, Moody MR, Wiernik PH (1972) Origin of infection in acute non-lymphocytic leukemia: significance of hospital acquisition of potential pathogens. Ann Intern Med 77:707–715

    Article  CAS  PubMed  Google Scholar 

  13. Hawthorn JW (1993) Critical appraisal of antimicrobials for prevention of infections in immunocompromised hosts. Hematol Oncol Clin North Am 7:1051–1099

    Google Scholar 

  14. Guiot HF, van Furth R (1984) Selective antimicrobial modulation of the intestinal flora. Prophylaxis against infection in neutropenic patients. Infection 12:1–4

    Article  CAS  PubMed  Google Scholar 

  15. Kerr KG (1999) The prophylaxis of bacterial infections in neutropenic patients. J Antimicrob Chemother 44:587–591

    Article  CAS  PubMed  Google Scholar 

  16. van Eys EJ, Berry DM, Crist W, Doering EJ, Fernbach DJ, Pullen J, Shuster J (1987) Effect of trimethoprim/sulfamethoxazole prophylaxis on outcome of childhood lymphocytic leukemia. A Pediatric Oncology Group Study. Cancer 59:19–23

    Article  PubMed  Google Scholar 

  17. Kovatch AL, Wald ER, Albo VC, Prin W, Orlando SJ, Wollman MR, Phebus CK, Shapiro ED (1985) Oral trimethoprim/sulfamethoxazole for prevention of bacterial infection during the induction phase of cancer chemotherapy in children. Pediatrics 76:754–760

    CAS  PubMed  Google Scholar 

  18. Goorin AM, Hershey BJ, Levin MJ, Siber GR, Gelber RD, Flynn K, Lew M, Beckett K, Blanding P, Sallan SE (1985) Use of trimethoprim/sulfamethoxazole to prevent bacterial infections in children with acute lymphoblastic leukemia. Pediatr Infect Dis 4:265–269

    Article  CAS  PubMed  Google Scholar 

  19. Gualtieri RJ, Donowitz GR, Kaiser DL, Hess CE, Sande MA (1983) Double-blind randomized study of prophylactic trimethoprim/sulfametoxazole in granulocytopenic patients with hematologic malignancies. Am J Med 74:934–940

    Article  CAS  PubMed  Google Scholar 

  20. Castagnola E, Zarri D, Caprino D, Losurdo G, Micalizzi C (2001) Cotrimoxazole prophylaxis of Pneumocystis carinii infection during the treatment of childhood acute lymphoblastic leukemia—beware non compliance in older children and adolescents. Support Care Cancer 9:552–553

    Article  CAS  PubMed  Google Scholar 

  21. Schrøder H, Agger KE, Rosthøj S, Carlsen NT, Schmiegelow K (2001) Antibacterial prophylaxis with trimethoprim-sulfamethoxazole during induction treatment for acute lymphoblastic leukemia. Dan Med Bull 48:275–277

    PubMed  Google Scholar 

  22. Cullen M, Steven N, Billingham L, Gaunt C, Hastings M, Simmonds P, Stuart N, Rea D, Bower M, Fernando I, Huddart R, Gollins S, Stanley A, Simple Investigation in Neutropenic Individuals of the Frequency of Infection after Chemotherapy +/− Antibiotic in a Number of Tumours (SIGNIFICANT) Trial Group (2005) Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas. N Engl J Med 353:988–998

    Article  CAS  PubMed  Google Scholar 

  23. Gafter-Gvili A, Fraser A, Paul M, Leibovici L (2005) Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. Ann Intern Med 142(12 Pt 1):979–995

    Article  PubMed  Google Scholar 

  24. Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, Allione B, D'Antonio D, Buelli M, Nosari AM, Cilloni D, Zuffa E, Cantaffa R, Specchia G, Amadori S, Fabbiano F, Deliliers GL, Lauria F, Foà R, Del Favero A, Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Infection Program (2005) Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Engl J Med 353:977–987

    Article  CAS  PubMed  Google Scholar 

  25. Freifeld AG, Sepkowitz KA, Martino P, Steven N, Billingham L, Cullen M, Billingham L, Cullen M, Baden LR (2006) Antibacterial prophylaxis in patients with cancer and neutropenia. N Engl J Med 354:90–94

    Article  PubMed  Google Scholar 

  26. Timmers GJ, Dijstelbloem Y, Simoons-Smit AM, van Winkelhoff AJ, Touw DJ, Vandenbroucke-Grauls CM, Huijgens PC (2004) Pharmacokinetics and effects on bowel and throat microflora of oral levofloxacin as antibacterial prophylaxis in neutropenic patients with haematological malignancies. Bone Marrow Transplant 33:847–853

    Article  CAS  PubMed  Google Scholar 

  27. Razonable RR, Litzow MR, Khaliq Y, Piper KE, Rouse MS, Patel R (2002) Bacteremia due to viridans group Streptococci with diminished susceptibility to levofloxacin among neutropenic patients receiving levofloxacin prophylaxis. Clin Infect Dis 34:1469–1474

    Article  CAS  PubMed  Google Scholar 

  28. Cruciani M, Concia E, Navarra A, Perversi L, Bonetti F, Aricò M, Nespoli L (1989) Prophylactic co-trimoxazole versus norfloxacin in neutropenic children-perspective randomized study. Infection 17:65–69

    Article  CAS  PubMed  Google Scholar 

  29. Yousef AA, Fryer CJ, Chedid FD, Abbas AA, Felimban SK, Khattab TM (2004) A pilot study of prophylactic ciprofloxacin during delayed intensification in children with acute lymphoblastic leukemia. Pediatr Blood Cancer 43:637–643

    Article  PubMed  Google Scholar 

  30. Mullen CA, Nair J, Sandesh S, Chan KW (2000) Fever and neutropenia in pediatric hematopoietic stem cell transplant patients. Bone Marrow Transplant 25:59–65

    Article  CAS  PubMed  Google Scholar 

  31. Laoprasopwattana K, Khwanna T, Suwankeeree P, Sujjanunt T, Tunyapanit W, Chelae S (2013) Ciprofloxacin reduces occurrence of fever in children with acute leukemia who develop neutropenia during chemotherapy. Pediatr Infect Dis J 32:e94–e98

    Article  PubMed  Google Scholar 

  32. National Cancer Institute. Levofloxacin in preventing infection in young patients receiving chemotherapy for acute leukemia or undergoing stem cell transplantation. Available at: http://www.cancer.gov/clinicaltrials/search/view?cdrid=695661&version=HealthProfessional#ContactInfo_CDR0000695661. Accessed 8 January 2013

  33. Kurt B, Flynn P, Shenep JL, Pounds S, Lensing S, Ribeiro RC, Pui CH, Razzouk BI, Rubnitz JE (2008) Prophylactic antibiotics reduce morbidity due to septicemia during intensive treatment for pediatric acute myeloid leukemia. Cancer 113:376–382

    Article  PubMed  Google Scholar 

  34. Castagnola E, Boni L, Giacchino M, Cesaro S, De Sio L, Garaventa A, Zanazzo G, Biddau P, Rossi MR, Schettini F, Bruzzi P, Viscoli C, Infectious Diseases Study Group of the Italian Association of Pediatric Hematology and Oncology (2003) A multicenter, randomized, double blind. placebo-controlled trial of amoxicillin/clavulanate for the prophylaxis of fever and infection in neutropenic children with cancer. Pediatr Infect Dis J 22:359–365

    PubMed  Google Scholar 

  35. Committee on Infectious Disease (2006) The use of systemic fluoroquinolones. Pediatrics 118:1287–1292

    Article  Google Scholar 

  36. Diorio C, Tomlinson D, Boydell KM, Regier DA, Ethier MC, Alli A, Alexander S, Gassas A, Taylor J, Kellow C, Mills D, Sung L (2012) Attitudes toward infection prophylaxis in pediatric oncology: a qualitative approach. PLoS One 7:e47815

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the Italian Ministry of Health (Bando Giovani Ricercatori 2009).

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Division of Pediatric Hematology and Oncology, Department of Hematology, Santo Spirito Hospital, Pescara, Italy

    V. Cecinati

  2. Pediatric Clinic 1, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via Commenda 9, 20122, Milan, Italy

    N. Principi & S. Esposito

  3. Hematology-Oncology Unit, IRCCS Bambino Gesù Hospital, Rome, Italy

    L. Brescia

Authors
  1. V. Cecinati
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. Principi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Brescia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Esposito
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Esposito.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cecinati, V., Principi, N., Brescia, L. et al. Antibiotic prophylaxis in children with cancer or who have undergone hematopoietic cell transplantation. Eur J Clin Microbiol Infect Dis 33, 1–6 (2014). https://doi.org/10.1007/s10096-013-1932-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-013-1932-7

Keywords

Search

Navigation