Management of Fever in Cancer Patients with Acquired Neutropenia

  • P. Eggimann
Conference paper
Part of the Yearbook of Intensive Care and Emergency Medicine book series (YEARBOOK, volume 1998)


During the past few decades, substantial progress in multidrug immunosuppressive and cytotoxic chemotherapeutic treatments have greatly improved the prognosis of most cancer patients. However, infectious complications due to acquired neutropenia have become a major medical issue, often requiring intensive care management. The infections may be lethal if empiric broad-spectrum treatment is not instituted at the first sign of infection. Although this is now considered standard practice, the selection and evaluation of the efficacy of antibiotic agents has generated considerable controversy for nearly 25 years. After reviewing some particularities of infection in neutropenic patients, this paper will discuss the options and suggest a comprehensive algorithm for the non-infectious diseases specialist.


Antimicrob Agent Neutropenic Patient Febrile Neutropenic Patient Neutropenic Cancer Patient Streptococcal Bacteremia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Mcgeer A, Feld R (1994) Epidemiology of infection in immunocompromised oncological patients. In: Balliere’s Clinical Infectious Diseases 1,pp 415–438Google Scholar
  2. 2.
    Hughes WT, Armstrong D, Bodey GP, et al (1990) Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. J Infect Dis 161: 381–396PubMedCrossRefGoogle Scholar
  3. 3.
    Bodey GP, Buckley M, Sathe YS, Freireich EJ (1966) Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med 64: 328–340PubMedGoogle Scholar
  4. 4.
    Schimpff SC (1995) Infections in cancer patients - diagnosis, prevention and treatment. In: Mandell GL, Douglas RG, Bennett JE (eds) Principles and practice of infectious diseases, 4th ed. Churchill Livingstone, New York, pp 2266–2275Google Scholar
  5. 5.
    Talcott GP, Siegel RD, Finberg R, et al (1992) Risk assessment in patients with cancer with fever and neutropenia: A prospective two-center validation of a prediction rule. J Clin Oncol 10: 316–322PubMedGoogle Scholar
  6. 6.
    Talcott GP, Finberg R, Mayer RJ, et al (1988) The medical course of patients with cancer with fever and neutropenia. Arch Intern Med 148: 2561–2568PubMedCrossRefGoogle Scholar
  7. 7.
    Pizzo PA (1993) Management of fever in patients with cancer and treatment-induced neutropenia. N Engl J Med 328: 1323–1332PubMedCrossRefGoogle Scholar
  8. 8.
    Bodey GP (1986) Infection in patients with cancer: A continuing association. Am J Med 81 (suppl 1A): 11–26PubMedCrossRefGoogle Scholar
  9. 9.
    Calandra T, Cometta A (1991) Antibiotic therapy for Gram-negative bacteremia. Infect Dis Clin North Am 5: 817–834PubMedGoogle Scholar
  10. 10.
    Hathorn JW, Lyke K (1997) Empirical treatment of febrile neutropenia: Evolution of current therapeutic approaches. Clin Infect Dis 24 (suppl 2): S256–sS265CrossRefGoogle Scholar
  11. 11.
    The EORTC International Antimicrobial Therapy Cooperative Group (1990) Gram-positive bacteraemia in granulocytopenic cancer patients. Eur J Cancer 26: 569–574CrossRefGoogle Scholar
  12. 12.
    Rolston KVI, Berkey P, Bodey GP, et al (1992) A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients. Arch Intern Med 152: 283–291PubMedCrossRefGoogle Scholar
  13. 13.
    Coullioud D, Van der Auwera P, Viot M, Lasset C (1993) Prospective multicentric study of the etiology of 1051 bacteremic episodes in 782 cancer patients. Cemic (french-belgian study club of infectious diseases in cancer). Support Care Cancer 1: 34–46PubMedCrossRefGoogle Scholar
  14. 14.
    Cometta A, Zinner SH, De Bock R, et al (1995) Piperacillin-tazobactam plus amikacin versus ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. Antimicrob Agents Chemother 39: 445–452PubMedGoogle Scholar
  15. 15.
    Cometta A, Calandra T, Gaya H, et al (1996) Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. Antimicrob Agents Chemother 40: 1108–1115PubMedGoogle Scholar
  16. 16.
    Winston DJ, Dudnick DV, Chapin M, Ho WG, Gale RP, Martin WJ (1983) Coagulase-negative staphylococcal bacteremia in patients receiving immunosuppressive therapy. Arch Intern Med 143: 32–36PubMedCrossRefGoogle Scholar
  17. 17.
    Bochud PY, Eggimann P, Calandra T, Van Melle G, Saghafi L, Francioli P (1994) Viridans strepto-coccal bacteremias in neutropenic cancer patients: clinical spectrum and risk factors. Clin Infect Dis 18: 25–31PubMedCrossRefGoogle Scholar
  18. 18.
    Bochud PY, Calandra T, Francioli P (1994) Bacteremia due to viridans streptococci in neutropenic patients: a review. Am J Med 97: 256–264PubMedCrossRefGoogle Scholar
  19. 19.
    Dybedal I, Lamvik J (1989) Respiratory insufficiency in acute leukemia following treatment with cytosine arabinoside and septicemia with streptococcus viridans. Eur J Haematol 42: 405–406PubMedGoogle Scholar
  20. 20.
    Karp JE, Merz WG, Hendricksen C, et al (1987) Oral norfloxacin for the prevention of gram- negative bacterial infections in patients with acute leukemia and granulocytopenia. Ann Intern Med 106: 1–7PubMedGoogle Scholar
  21. 21.
    International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer (1994) Reduction of fever and streptococcal bacteremia in granulocytopenic patients with cancer. JAMA 272: 1183–1189CrossRefGoogle Scholar
  22. 22.
    GIMEMA Infection Program (1991) Prevention of bacterial infection in neutropenic patients with hematologic malignancies: a randomized, multicenter trial comparing norfloxacin with ciprofloxacin. Ann Intern Med 117: 7–12Google Scholar
  23. 23.
    Bow EJ, Manciell LA, Louie TJ, et al (1996) Quinolone-based antibacterial chemoprophylaxis in neutropenic patients: Effect of augmented gram-positive activity on infectious morbidity. Ann Intern Med 125: 183–190PubMedGoogle Scholar
  24. 24.
    Anaissie E (1992) Opportunistic mycoses in the immunocompromised host: experience at a cancer center and review. Clin Infect Dis 14 (suppl 1): S43–S53CrossRefGoogle Scholar
  25. 25.
    EORTC International Antimicrobial Therapy Cooperative Group (1989) Empiric antifungal therapy in febrile granulocytopenic patients. Am J Med 86: 668–672CrossRefGoogle Scholar
  26. 26.
    Bodey G, Bueltmann B, Duguid W, et al (1992) Fungal infections in cancer patients: an inter-national autopsy survey. Eur J Clin Microbiol Infect Dis 11: 99–109PubMedCrossRefGoogle Scholar
  27. 27.
    Schaffner A (1994) Prophylaxis and treatment of fungal infections in cancer patients. In: Balliere’s Clinical Infectious Diseases 1,pp 499–522Google Scholar
  28. 28.
    Winston DJ, Chandrasekar PH, Lazarus HM, et al (1993) Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double- blind, multicenter trial. Ann Intern Med 118: 495–503PubMedGoogle Scholar
  29. 29.
    Menichetti F, Del Favero A, Martino P, et al (1994) Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B. Ann Intern Med 120: 913–918PubMedGoogle Scholar
  30. 30.
    Powderly WG, Finkelstein D, Feinberg J, et al (1995) A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. N Engl J Med 332: 700–705PubMedCrossRefGoogle Scholar
  31. 31.
    Novakova I, Donnelly JP, De Pauw B (1991) Ceftazidime as monotherapy or combined with teicoplanin for initial empiric treatment of presumed bacteremia in febrile granulocytopenic patients. Antimicrob Agents Chemother 35: 672–678PubMedGoogle Scholar
  32. 32.
    Gold D, Corey (1987) Acyclovir prophylaxis for herpes simplex virus infection. Antimicrob Agents Chemother 31: 361–367PubMedGoogle Scholar
  33. 33.
    Reusser P (1994) Prophylaxis and treatment of herpes virus infections in immunocompromised cancer patients. In: Balliere’s Clinical Infectious Diseases 1,pp 523–544Google Scholar
  34. 34.
    Jones RN, Thornsberry C, Barry AL (1984) In vitro evaluation of HR810, a new wide-spectrum aminothiazol a-methoxyimino cephalosporin. Antimicrob Agents Chemother 25: 710–718PubMedGoogle Scholar
  35. 35.
    EORTC International Antimicrobial Therapy Cooperative Group (1987) Ceftazidime combined with a short or long course of amikacin for empirical therapy of Gram-negative bacteremia in cancer patients with granulocytopenia. N Engl J Med 317: 1692–1698CrossRefGoogle Scholar
  36. 36.
    Klastersky J, Zinner SH, Calandra T, et al (1988) Empirical antimicrobial therapy for febrile granulocytopenic cancer patients: lessons from four EORTC trials. Eur J Cancer Clin Oncol 24: 535–545CrossRefGoogle Scholar
  37. 37.
    Meunier F, Zinner SH, Gaya H, et al (1991) Prospective randomized evaluation of ciprofloxacin versus piperacillin plus amikacin for empiric antibiotic therapy of febrile granulocytopenic cancer patients with lymphomas and solid tumors. Antimicrob Agents Chemother 35: 873–878PubMedGoogle Scholar
  38. 38.
    The EORTC International Antimicrobial Therapy Cooperative Group (1991) Vancomycin added to empirical combination antibiotic therapy for fever in granulocytopenic cancer patients. J Infect Dis 163: 951–958CrossRefGoogle Scholar
  39. 39.
    EORTC International Antimicrobial Therapy Cooperative Group (1993) The efficacy and toxicity of single daily dose of amikacin and ceftriaxone versus multiple daily doses of amikacin and ceftazidime for infection in patients with cancer and granulocytopenia. Ann Intern Med 119: 584–593Google Scholar
  40. 40.
    Karp JE, Hick JD, Angelopulos C, et al (1986) Empiric use of vancomycin during prolonged treatment induced granulocytopenia. Am J Med 81: 237–242PubMedCrossRefGoogle Scholar
  41. 41.
    Rubin M, Hathorn JW, Marshall D, Gress J, Steinberg SM, Pizzo PA (1988) Gram-positive infections and the use of vancomycin in 550 episodes of fever and neutropenia. Ann Intern Med 108: 30–35PubMedGoogle Scholar
  42. 42.
    Ramphai R, Bolger M, Obion DJ, et al (1992) Vancomycin is not an essential component of the initial empiric treatment regimen for febrile neutropenic patients receiving ceftazidime: a randomized prospective study. Antimicrob Agents Chemother 36: 1062–1067Google Scholar
  43. 43.
    Edmond MB, Wenzel RP, Pasculle AW (1996) Vancomycin-resistant staphylococcus aureus: perspectives on measures needed for control. Ann Intern Med 124: 329–334PubMedGoogle Scholar
  44. 44.
    Coque TM, Tomayko JF, Ricke SC, Okhyusen PC, Murray BE (1996) Vancomycin-resistant enterococci from nosocomial, community, and animal sources in the united states. Antimicrob Agents Chemother 40: 2605–2609PubMedGoogle Scholar
  45. 45.
    Sanders JW, Powe NR, Moore RD, et al (1991) Ceftazidime monotherapy for empiric treatment of febrile neutropenic patients: a metaanalysis. J Infect Dis 164: 907–916PubMedCrossRefGoogle Scholar
  46. 46.
    Eggimann P, Glauser MP, Aoun M, Meunier F, Calandra T (1993) Cefepime monotherapy for the empirical treatment of fever in granulocytopenic cancer patients. J Antimicrob Chemother 32 (Suppl B): 151–163PubMedGoogle Scholar
  47. 47.
    Ramphal R, Gucalp R, Rotstein C, Cimino M, Obion D (1996) Clinical experience with single agent and combination regimens in the management of infection in the febrile neutropenic patient. Am J Med 100: 83S–89SPubMedCrossRefGoogle Scholar
  48. 48.
    Malik I A, Khan WA, Karim M, Aziz Z, Khan MA (1995) Feasibility of outpatient management of fever in cancer patients with low-risk neutropenia: Results of a prospective randomized trial. Am J Med 98: 224–231PubMedCrossRefGoogle Scholar
  49. 49.
    Freifeld AG, Pizzo PA (1996) The outpatient management of febrile neutropenia in cancer patients. Oncology 10: 599–612PubMedGoogle Scholar
  50. 50.
    Escalante CP, Rubenstein EB, Rolston KV (1997) Outpatient antibiotic therapy for febrile episodes in low-risk neutropenic patients with cancer. Cancer Invest 15: 237–242PubMedCrossRefGoogle Scholar
  51. 51.
    Freifeld A, Pizzo P (1997) Use of fluoroquinolones for empirical management of febrile neutropenia in pediatric cancer patients. Pediatr Infect Dis J 16: 140–146PubMedCrossRefGoogle Scholar
  52. 52.
    Cometta A, Baumgartner JD, Lew D, et al (1994) Prospective randomized comparison of imipenem monotherapy with imipenem plus netilmicin for treatment of severe infections in non- neutropenic patients. Antimicrob Agents Chemother 38: 1309–1313PubMedGoogle Scholar
  53. 53.
    The meropenem study group of Leuven (1995) Equivalent efficacies of meropenem and ceft-azidime as empirical monotherapy of febrile neutropenic patients. J Antimicrob Chemother 36: 185–200CrossRefGoogle Scholar
  54. 54.
    Santolaya ME, Villarroel M, Avendano LF, Cofre J (1997) Discontinuation of antimicrobial therapy for febrile, neutropenic children with cancer: a prospective study. Clin Infect Dis 25: 92–97PubMedCrossRefGoogle Scholar
  55. 55.
    Clift RA, Sanders JE, Thomas ED, Buckner CD (1978) Granulocyte transfusions for the prevention of infection in patients receiving bone-marrow transplant. N Engl J Med 298: 1052–1057PubMedCrossRefGoogle Scholar
  56. 56.
    Strauss RG, Conett JE, Gale RP, et al (1981) A controlled trial of prophylactic granulocyte transfusions during initial induction chemotherapy for acute myelogenous leukemia. N Engl J Med 305: 597–638PubMedCrossRefGoogle Scholar
  57. 57.
    Cohen J, Heumann D, Glauser MP (1995) Do monoclonal antibodies and anticytokines still have a future in infectious diseases? Am J Med 99: 45S–52SPubMedCrossRefGoogle Scholar
  58. 58.
    Cohen J, Carlet J (1996) Intersept: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International sepsis trial study group. Crit Care Med 24: 1431–1440PubMedCrossRefGoogle Scholar
  59. 59.
    Fisher CJ Jr, Agosti JM, Opal SM, et al (1996) Treatment of septic shock with the tumor necrosis factor receptor:fc fusion protein. The soluble tnf receptor sepsis study group. N Engl J Med 334: 1697–1702PubMedCrossRefGoogle Scholar
  60. 60.
    Gardner P, Schaffner W (1993) Immunization of adults. N Engl J Med 328: 1252–1258PubMedCrossRefGoogle Scholar
  61. 61.
    Fedson DS (1994) Adult immunization. Summary of the national vaccine advisory committee report. JAMA 272: 1133–1137PubMedCrossRefGoogle Scholar
  62. 62.
    American society of clinical oncology (1994) Recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. J Clin Oncol 12: 2471–2508Google Scholar
  63. 63.
    Boogaerts M, Cavalli F, Cortes-Funes H, et al (1995) Granulocyte growth factors: achieving a consensus. Ann Oncol 6: 237–244PubMedGoogle Scholar
  64. 64.
    Freifeld A, Pizzo P (1995) Colony-stimulating factors and neutropenia: intersection of data and clinical relevance. J Natl Cancer Inst 87: 781–782PubMedCrossRefGoogle Scholar
  65. 65.
    Pizzo PA (1995) Empiric therapy and prevention of infection in the immunocompromised host. In: Mandell GL, Bennett JE, Dolin R (eds) Principles and practice of infectious diseases. 4th ed. Churchill Livingstone, New York, pp 2686–2696Google Scholar
  66. 66.
    EORTC International Antimicrobial Therapy Cooperative Group (1984) Trimethoprim-sulfa-methoxazole in the prevention of infection in neutropenic patients. J Infect Dis 150: 372–379CrossRefGoogle Scholar
  67. 67.
    Maschmeyer G (1993) Use of the quinolones for the prophylaxis and therapy of infections in immunocompromised hosts. Drugs 45 (Suppl 3): 73–80PubMedCrossRefGoogle Scholar
  68. 68.
    Cometta A, Calandra T, Bille J, Glauser MP (1994) Escherichia coli resistant to fluoroquinolones in patients with cancer and neutropenia. N Engl J Med 330: 1240–1241PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1998

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  • P. Eggimann

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