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Prophylaxis with levofloxacin: bacterial infections and antimicrobial resistance in hematological malignancies* * See paper by Lopes LA et al. on pages 35-42. Prophylaxis with levofloxacin: impact on bacterial susceptibility and epidemiology in a hematopoietic stem cell transplant unit

Studies evaluating bacterial prophylaxis of patients under high risk for the development of febrile neutropenia have been published since the 1980s.11. Bodey GP. The treatment of febrile neutropenia: from the dark age to the present. Support Care Cancer. 1997;5(5):351-7.

2. Cruciani M, Rampazzo R, Malena M, Lazzarini L, Todeschini G, Messori A, et al. Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis. Clin Infect Dis. 1996;23(4):795-805. Comment in: Clin Infect Dis. 1997;25(2):346-8.
-33. Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, et al. Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Infection Program. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Eng J Med. 2005;353(10):977-87. Initially, trimethoprim with sulfamethoxazole was used, but this is associated with an unacceptable risk of myelosuppression. Thus, fluoroquinolones became the treatment of choice worldwide, due to their good oral tolerability, broad antimicrobial spectrum, bactericidal activity, ability to preserve anaerobic gut microorganisms, and lack of myelotoxicity. Ciprofloxacin was initially used in this scenario, but the need to treat Streptococcus viridans led to a progressive trend to prescribing levofloxacin due to its better activity against this microorganism.44. Gafter-Givili A, Paul M, Fraser A, Leibovici L. Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. Ann Intern Med. 2005;142(12 Pt 1):979-95.

Recent studies suggest that antibacterial prophylaxis with levofloxacin should be started when a neutropenia episode, secondary to chemotherapy, is expected. Decreasing rates of febrile neutropenic episodes and even all-cause mortality have been correlated with this approach.33. Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, et al. Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Infection Program. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Eng J Med. 2005;353(10):977-87.,55. Cullen M, Baijal S. Prevention of febrile neutropenia: use of prophylactic antibiotics. British Journal of Cancer 2009;101(Supl 1):S11-4.,66. van de Wetering MD, de Witte MA, Kremer LC, et al. Efficacy of oralprophylactic antibiotics in neutropenic afebrile oncology patients: a systematic review of randomised controlled trials. Eur J Cancer. 2005;41(1):1372-82. However, two aspects of this widely practiced procedure remain controversial and under discussion. First, it appears that the greatest benefit of antibiotic prophylaxis is restricted to patients who are expected to develop long and severe episodes of neutropenia (longer than seven days with neutrophils < 100 × 109 cells/L).77. Almyroudis NG, Segal BH. Antibacterial prophylaxis in patients with cancer and neutropenia. N Engl J Med. 2006;354(1):90-4; author reply 90-4.,88. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. 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. 2011;52(4):e56-93. Second, increasing rates of fluoroquinolone resistance in this group of patients have been described in the medical literature, including in hematological services where this routine was adopted. The widespread use of antimicrobials in incorrectly selected patient populations and the rise in bacterial resistance to these drugs exemplify a well-known phenomenon in the field of antimicrobial therapy. Indeed, the massive use of fluoroquinolones for prophylaxis and the emergence of bacterial resistance have already been noted in respiratory and genitourinary diseases.99. Flowers CR, Seidenfeld J, Bow EJ, Karten C, Gleason C, Hawley DK, et al. Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2013;31(6):794-810.

10. Maraffi T, Piffer F, Cosentini F. Prophylatic antibiotic in chronic obstructive pulmonary disease. Ther Adv Resp Dis. 2010;4(3):135-42.
-1111. Steensels D, Slabbaert K, De Wever L, Veermerch P, Van Poppel H, Verhaegen J. Fluoroquinolone-resistant E. coli in intestinal flora of patients undergoing transrectal ultrasound-guided prostate biopsy - should we reassess our practices for antibiotic prophylaxis?. Clin Microbiol Infect. 2012;18(6):575-81.

Thus, efforts in implementing protocols in order to select patients at real risk for the development of long and severe febrile neutropenic episodes are urged. Patients submitted to hematopoietic stem cell transplants and those in the conditioning period of acute myeloid leukemia chemotherapy are at the highest risk of developing long and severe episodes of febrile neutropenia, and are therefore appropriate candidates to receive antimicrobial prophylaxis.88. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. 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. 2011;52(4):e56-93.,99. Flowers CR, Seidenfeld J, Bow EJ, Karten C, Gleason C, Hawley DK, et al. Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2013;31(6):794-810. This measure is able to decrease fluoroquinolone exposure in thousands of patients and potentially contribute to control bacterial resistance related to antimicrobial selective pressure.1010. Maraffi T, Piffer F, Cosentini F. Prophylatic antibiotic in chronic obstructive pulmonary disease. Ther Adv Resp Dis. 2010;4(3):135-42.,1111. Steensels D, Slabbaert K, De Wever L, Veermerch P, Van Poppel H, Verhaegen J. Fluoroquinolone-resistant E. coli in intestinal flora of patients undergoing transrectal ultrasound-guided prostate biopsy - should we reassess our practices for antibiotic prophylaxis?. Clin Microbiol Infect. 2012;18(6):575-81. In this issue of the Revista Brasileira de Hematologia e Hemoterapia, Lopes et al. present a study on the use of prophylaxis with levofloxacin in a hematopoietic stem cell transplant unit.1212. Lopes LA, Veroneze I, Burgardt CI, Stier C. Prophylaxis with levofloxacin: impact on bacterial susceptibility and epidemiology in a hematopoietic stem cell transplant unit. Rev Bras Hematol Hemoter. 2014;36(1):35-42.

REFERENCES

  • 1
    Bodey GP. The treatment of febrile neutropenia: from the dark age to the present. Support Care Cancer. 1997;5(5):351-7.
  • 2
    Cruciani M, Rampazzo R, Malena M, Lazzarini L, Todeschini G, Messori A, et al. Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis. Clin Infect Dis. 1996;23(4):795-805. Comment in: Clin Infect Dis. 1997;25(2):346-8.
  • 3
    Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, et al. Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Infection Program. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Eng J Med. 2005;353(10):977-87.
  • 4
    Gafter-Givili A, Paul M, Fraser A, Leibovici L. Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. Ann Intern Med. 2005;142(12 Pt 1):979-95.
  • 5
    Cullen M, Baijal S. Prevention of febrile neutropenia: use of prophylactic antibiotics. British Journal of Cancer 2009;101(Supl 1):S11-4.
  • 6
    van de Wetering MD, de Witte MA, Kremer LC, et al. Efficacy of oralprophylactic antibiotics in neutropenic afebrile oncology patients: a systematic review of randomised controlled trials. Eur J Cancer. 2005;41(1):1372-82.
  • 7
    Almyroudis NG, Segal BH. Antibacterial prophylaxis in patients with cancer and neutropenia. N Engl J Med. 2006;354(1):90-4; author reply 90-4.
  • 8
    Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. 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. 2011;52(4):e56-93.
  • 9
    Flowers CR, Seidenfeld J, Bow EJ, Karten C, Gleason C, Hawley DK, et al. Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2013;31(6):794-810.
  • 10
    Maraffi T, Piffer F, Cosentini F. Prophylatic antibiotic in chronic obstructive pulmonary disease. Ther Adv Resp Dis. 2010;4(3):135-42.
  • 11
    Steensels D, Slabbaert K, De Wever L, Veermerch P, Van Poppel H, Verhaegen J. Fluoroquinolone-resistant E. coli in intestinal flora of patients undergoing transrectal ultrasound-guided prostate biopsy - should we reassess our practices for antibiotic prophylaxis?. Clin Microbiol Infect. 2012;18(6):575-81.
  • 12
    Lopes LA, Veroneze I, Burgardt CI, Stier C. Prophylaxis with levofloxacin: impact on bacterial susceptibility and epidemiology in a hematopoietic stem cell transplant unit. Rev Bras Hematol Hemoter. 2014;36(1):35-42.
  • *
    See paper by Lopes LA et al. on pages 35-42.

Publication Dates

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    Jan-Feb 2014
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