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Treatment and prevention of neutropenic fever syndromes in adult cancer patients at low risk for complications

Eric Bow, MD
Section Editor
Kieren A Marr, MD
Deputy Editor
Anna R Thorner, MD


Cancer patients receiving cytotoxic antineoplastic therapy sufficient to adversely affect myelopoiesis and the developmental integrity of the gastrointestinal mucosa are at risk for invasive infection due to colonizing bacteria or fungi that translocate across intestinal mucosal surfaces. Since the magnitude of the neutrophil-mediated component of the inflammatory response may be muted in neutropenic patients [1], an elevated body temperature may be the earliest and only sign of infection. It is critical to recognize neutropenic fever and associated sepsis syndromes early and to initiate empiric systemic antibacterial therapy promptly in order to avoid progression to a sepsis syndrome and possibly death.

The treatment and prevention of neutropenic fever syndromes in adult cancer patients at low risk for complications will be reviewed here. The treatment and prevention of neutropenic fever in adults at high risk for complications are discussed separately. An overview of neutropenic fever syndromes, the risk assessment of patients with neutropenic fever, the diagnostic approach to patients presenting with neutropenic fever, and the use of colony stimulating factors in patients with chemotherapy-induced neutropenia are also discussed elsewhere. (See "Treatment of neutropenic fever syndromes in adults with hematologic malignancies and hematopoietic cell transplant recipients (high-risk patients)" and "Prophylaxis of infection during chemotherapy-induced neutropenia in high-risk adults" and "Prophylaxis of invasive fungal infections in adults with hematologic malignancies" and "Prophylaxis of invasive fungal infections in adult hematopoietic cell transplant recipients" and "Prevention of infections in hematopoietic cell transplant recipients" and "Overview of neutropenic fever syndromes" and "Risk assessment of adults with chemotherapy-induced neutropenia" and "Diagnostic approach to the adult cancer patient with neutropenic fever" and "Use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation".)

Neutropenic fever in children is also presented separately. (See "Fever in children with chemotherapy-induced neutropenia".)


Guidelines have been developed for the prevention and management of fever in neutropenic patients with cancer [2-8]. The recommendations below are generally in keeping with the 2010 Infectious Diseases Society of America (IDSA) guidelines [2] and the 2013 American Society of Clinical Oncology (ASCO) guidelines [7]. Links to guidelines are provided separately. (See 'Society guideline links' below.)

It should be noted that our approach differs slightly from the approach of the IDSA and ASCO because we consider low-risk patients to be those who are anticipated to have an absolute neutrophil count <500 cells/microL (rather than <100 cells/microL) for ≤7 days. The rationale for choosing this threshold is discussed below. (See 'Risk of serious complications' below.)

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Literature review current through: Nov 2017. | This topic last updated: Dec 08, 2015.
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  1. Sickles EA, Greene WH, Wiernik PH. Clinical presentation of infection in granulocytopenic patients. Arch Intern Med 1975; 135:715.
  2. Freifeld AG, Bow EJ, Sepkowitz KA, 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:e56.
  3. Link H, Böhme A, Cornely OA, et al. Antimicrobial therapy of unexplained fever in neutropenic patients--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), Study Group Interventional Therapy of Unexplained Fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG-German Cancer Society). Ann Hematol 2003; 82 Suppl 2:S105.
  4. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related infections. Version 2.2014. http://www.nccn.org (Accessed on November 06, 2014).
  5. Infectious Diseases Society of Taiwan, Hematology Society of Taiwan, Medical Foundation in Memory Dr. Deh-Lin Cheng, et al. Guidelines for the use of antimicrobial agents in patients with febrile neutropenia in Taiwan. J Microbiol Immunol Infect 2005; 38:455.
  6. Masaoka T. Evidence-based recommendations for antimicrobial use in febrile neutropenia in Japan: executive summary. Clin Infect Dis 2004; 39 Suppl 1:S49.
  7. Flowers CR, Seidenfeld J, Bow EJ, 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; 31:794.
  8. Weissinger F, Auner HW, Bertz H, et al. Antimicrobial therapy of febrile complications after high-dose chemotherapy and autologous hematopoietic stem cell transplantation--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 2012; 91:1161.
  9. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common terminology criteria for adverse events (CTCAE). http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf (Accessed on February 16, 2012).
  10. Klastersky J, Paesmans M, Rubenstein EB, et al. The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol 2000; 18:3038.
  11. Kamana M, Escalante C, Mullen CA, et al. Bacterial infections in low-risk, febrile neutropenic patients. Cancer 2005; 104:422.
  12. Paesmans M, Klastersky J, Maertens J, et al. Predicting febrile neutropenic patients at low risk using the MASCC score: does bacteremia matter? Support Care Cancer 2011; 19:1001.
  13. Sievert DM, Ricks P, Edwards JR, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010. Infect Control Hosp Epidemiol 2013; 34:1.
  14. Satlin MJ, Calfee DP, Chen L, et al. Emergence of carbapenem-resistant Enterobacteriaceae as causes of bloodstream infections in patients with hematologic malignancies. Leuk Lymphoma 2013; 54:799.
  15. Bow EJ. There should be no ESKAPE for febrile neutropenic cancer patients: the dearth of effective antibacterial drugs threatens anticancer efficacy. J Antimicrob Chemother 2013; 68:492.
  16. Morris PG, Hassan T, McNamara M, et al. Emergence of MRSA in positive blood cultures from patients with febrile neutropenia--a cause for concern. Support Care Cancer 2008; 16:1085.
  17. McKenzie H, Hayes L, White K, et al. Chemotherapy outpatients' unplanned presentations to hospital: a retrospective study. Support Care Cancer 2011; 19:963.
  18. Bell MS, Scullen P, McParlan D, et al. Neutropenic sepsis guidelines. Northern Ireland Cancer Network, Belfast 2010. p. 1-11.
  19. Sickles EA, Young VM, Greene WH, Wiernik PH. Pneumonia in acute leukemia. Ann Intern Med 1973; 79:528.
  20. Sepkowitz KA. Treatment of patients with hematologic neoplasm, fever, and neutropenia. Clin Infect Dis 2005; 40 Suppl 4:S253.
  21. Lazarus HM, Creger RJ, Gerson SL. Infectious emergencies in oncology patients. Semin Oncol 1989; 16:543.
  22. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36:296.
  23. Chemotherapy services in England: Ensuring quality and safety. National Chemotherapy Advisory Group, London 2009.
  24. Rosa RG, Goldani LZ. Cohort study of the impact of time to antibiotic administration on mortality in patients with febrile neutropenia. Antimicrob Agents Chemother 2014; 58:3799.
  25. Rolston KV. Challenges in the treatment of infections caused by gram-positive and gram-negative bacteria in patients with cancer and neutropenia. Clin Infect Dis 2005; 40 Suppl 4:S246.
  26. Viscoli C, Castagnola E. Planned progressive antimicrobial therapy in neutropenic patients. Br J Haematol 1998; 102:879.
  27. Viscoli C, Varnier O, Machetti M. Infections in patients with febrile neutropenia: epidemiology, microbiology, and risk stratification. Clin Infect Dis 2005; 40 Suppl 4:S240.
  28. Pagano L, Caira M, Nosari A, et al. Etiology of febrile episodes in patients with acute myeloid leukemia: results from the Hema e-Chart Registry. Arch Intern Med 2011; 171:1502.
  29. de Naurois J, Novitzky-Basso I, Gill MJ, et al. Management of febrile neutropenia: ESMO Clinical Practice Guidelines. Ann Oncol 2010; 21 Suppl 5:v252.
  30. Freifeld A, Marchigiani D, Walsh T, et al. A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy. N Engl J Med 1999; 341:305.
  31. Kern WV, Cometta A, De Bock R, et al. Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med 1999; 341:312.
  32. Vidal L, Ben Dor I, Paul M, et al. Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients. Cochrane Database Syst Rev 2013; :CD003992.
  33. Kern WV, Marchetti O, Drgona L, et al. Oral antibiotics for fever in low-risk neutropenic patients with cancer: a double-blind, randomized, multicenter trial comparing single daily moxifloxacin with twice daily ciprofloxacin plus amoxicillin/clavulanic acid combination therapy--EORTC infectious diseases group trial XV. J Clin Oncol 2013; 31:1149.
  34. Slavin MA, Thursky KA. Outpatient therapy for fever and neutropenia is safe but implementation is the key. J Clin Oncol 2013; 31:1128.
  35. Freifeld AG, Sepkowitz KA. No place like home? Outpatient management of patients with febrile neutropenia and low risk. J Clin Oncol 2011; 29:3952.
  36. Elting LS, Lu C, Escalante CP, et al. Outcomes and cost of outpatient or inpatient management of 712 patients with febrile neutropenia. J Clin Oncol 2008; 26:606.
  37. Hendricks AM, Loggers ET, Talcott JA. Costs of home versus inpatient treatment for fever and neutropenia: analysis of a multicenter randomized trial. J Clin Oncol 2011; 29:3984.
  38. Freifeld A, Sankaranarayanan J, Ullrich F, Sun J. Clinical practice patterns of managing low-risk adult febrile neutropenia during cancer chemotherapy in the USA. Support Care Cancer 2008; 16:181.
  39. Teuffel O, Ethier MC, Alibhai SM, et al. Outpatient management of cancer patients with febrile neutropenia: a systematic review and meta-analysis. Ann Oncol 2011; 22:2358.
  40. Talcott JA, Yeap BY, Clark JA, et al. Safety of early discharge for low-risk patients with febrile neutropenia: a multicenter randomized controlled trial. J Clin Oncol 2011; 29:3977.
  41. Innes HE, Smith DB, O'Reilly SM, et al. Oral antibiotics with early hospital discharge compared with in-patient intravenous antibiotics for low-risk febrile neutropenia in patients with cancer: a prospective randomised controlled single centre study. Br J Cancer 2003; 89:43.
  42. Innes H, Billingham L, Gaunt C, et al. Management of febrile neutropenia in the United Kingdom: time for a national trial? Br J Cancer 2005; 93:1324.
  43. Girmenia C, Russo E, Carmosino I, et al. Early hospital discharge with oral antimicrobial therapy in patients with hematologic malignancies and low-risk febrile neutropenia. Ann Hematol 2007; 86:263.
  44. Sebban C, Dussart S, Fuhrmann C, et al. Oral moxifloxacin or intravenous ceftriaxone for the treatment of low-risk neutropenic fever in cancer patients suitable for early hospital discharge. Support Care Cancer 2008; 16:1017.
  45. Bow EJ. Neutropenic fever syndromes in patients undergoing cytotoxic therapy for acute leukemia and myelodysplastic syndromes. Semin Hematol 2009; 46:259.
  46. Schimpff S, Satterlee W, Young VM, Serpick A. Empiric therapy with carbenicillin and gentamicin for febrile patients with cancer and granulocytopenia. N Engl J Med 1971; 284:1061.
  47. Klastersky J, Cappel R, Debusscher L. Evaluation of gentamicin with carbenicillin in infections due to gram-negative bacilli. Curr Ther Res Clin Exp 1971; 13:174.
  48. Klastersky J. The changing face of febrile neutropenia-from monotherapy to moulds to mucositis. Why empirical therapy? J Antimicrob Chemother 2009; 63 Suppl 1:i14.
  49. Gram-negative bacteremia, clinical, laboratory and therapeutic observations. Arch Intern Med 1962; 110:856.
  50. Kuderer NM, Dale DC, Crawford J, et al. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 2006; 106:2258.
  51. Bow EJ. Point: fluoroquinolone-based antibacterial chemoprophylaxis in neutropenic cancer patients works for defined outcomes in defined populations, but must be used wisely. J Natl Compr Canc Netw 2004; 2:433.
  52. Bow EJ. Prophylaxis. In: Managing Infections in Patients with Hematological Malignancies, Kleinberg M (Ed), Humana Press, 2009. p.259.
  53. Cullen M, Steven N, Billingham L, et al. Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas. N Engl J Med 2005; 353:988.
  54. Baden LR. Prophylactic antimicrobial agents and the importance of fitness. N Engl J Med 2005; 353:1052.
  55. Pépin J, Saheb N, Coulombe MA, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis 2005; 41:1254.
  56. Kern WV, Andriof E, Oethinger M, et al. Emergence of fluoroquinolone-resistant Escherichia coli at a cancer center. Antimicrob Agents Chemother 1994; 38:681.
  57. Carratalá J, Fernández-Sevilla A, Tubau F, et al. Emergence of quinolone-resistant Escherichia coli bacteremia in neutropenic patients with cancer who have received prophylactic norfloxacin. Clin Infect Dis 1995; 20:557.
  58. Bow EJ. Fluoroquinolones, antimicrobial resistance and neutropenic cancer patients. Curr Opin Infect Dis 2011; 24:545.
  59. Lubel JS, Angus PW. Hepatitis B reactivation in patients receiving cytotoxic chemotherapy: diagnosis and management. J Gastroenterol Hepatol 2010; 25:864.
  60. Firpi RJ, Nelson DR. Viral hepatitis: manifestations and management strategy. Hematology Am Soc Hematol Educ Program 2006; :375.