Advertisement

Infections in Cancer

  • Andrea J. Zimmer
  • Alison G. Freifeld
Chapter

Infections are an important cause of morbidity and mortality in the oncology population. Individual’s risk of various infections is dependent on a multitude factors, particularly the type of cancer, sites involved, treatment regimen, procedures, and neutropenia. Preexisting comorbidities such as obesity, diabetes, and lung, kidney, and liver disease are also important factors to take into consideration, as are age, malnutrition, and deconditioning. Neutropenia remains the most important risk factor, with increased depth and duration associated with higher incidence of infection. In this chapter, we will be discussing infections in patients with solid tumors and hematologic malignancies, with the exception of hematopoietic stem cell transplant (HSCT) recipients, as this population will be discussed in a separate chapter.

Keywords

Febrile neutropenia Cancer treatment Chemotherapy Bacteremia Invasive fungal infections 

References

  1. 1.
    Kuderer NM, et al. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer. 2006;106(10):2258–66.CrossRefPubMedGoogle Scholar
  2. 2.
    Bodey GP, et al. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966;64(2):328–40.CrossRefPubMedGoogle Scholar
  3. 3.
    Nesher L, Rolston KV. The current spectrum of infection in cancer patients with chemotherapy related neutropenia. Infection. 2014;42(1):5–13.CrossRefPubMedGoogle Scholar
  4. 4.
    Freifeld AG, 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.CrossRefPubMedGoogle Scholar
  5. 5.
    van der Velden WJ, et al. Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis. Br J Haematol. 2014;167(4):441–52.CrossRefPubMedGoogle Scholar
  6. 6.
    Epstein JB, et al. Oral complications of cancer and cancer therapy: from cancer treatment to survivorship. CA Cancer J Clin. 2012;62(6):400–22.CrossRefPubMedGoogle Scholar
  7. 7.
    Crawford J, Dale DC, Lyman GH. Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management. Cancer. 2004;100(2):228–37.CrossRefPubMedGoogle Scholar
  8. 8.
    Crawford J, et al. Risk and timing of neutropenic events in adult cancer patients receiving chemotherapy: the results of a prospective nationwide study of oncology practice. J Natl Compr Cancer Netw. 2008;6(2):109–18.CrossRefGoogle Scholar
  9. 9.
    Lyman GH, et al. Predicting individual risk of neutropenic complications in patients receiving cancer chemotherapy. Cancer. 2011;117(9):1917–27.CrossRefPubMedGoogle Scholar
  10. 10.
    Lyman GH, Lyman CH, Agboola O. Risk models for predicting chemotherapy-induced neutropenia. Oncologist. 2005;10(6):427–37.CrossRefPubMedGoogle Scholar
  11. 11.
    Paul M, et al. Empirical antibiotic monotherapy for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2006;57(2):176–89.CrossRefPubMedGoogle Scholar
  12. 12.
    Schimpff SC. Empiric antibiotic therapy for granulocytopenic cancer patients. Am J Med. 1986;80(5C):13–20.PubMedGoogle Scholar
  13. 13.
    Freifeld A, 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(5):305–11.CrossRefPubMedGoogle Scholar
  14. 14.
    Klastersky J, et al. Bacteraemia in febrile neutropenic cancer patients. Int J Antimicrob Agents. 2007;30(Suppl 1):S51–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Schimpff SC. Overview of empiric antibiotic therapy for the febrile neutropenic patient. Rev Infect Dis. 1985;7(Suppl 4):S734–40.CrossRefPubMedGoogle Scholar
  16. 16.
    Paul M, et al. Anti-pseudomonal beta-lactams for the initial, empirical, treatment of febrile neutropenia: comparison of beta-lactams. Cochrane Database Syst Rev. 2010;11:CD005197.Google Scholar
  17. 17.
    Cometta A, et al. Vancomycin versus placebo for treating persistent fever in patients with neutropenic cancer receiving piperacillin-tazobactam monotherapy. Clin Infect Dis. 2003;37(3):382–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Vancomycin added to empirical combination antibiotic therapy for fever in granulocytopenic cancer patients. European Organization for Research and Treatment of Cancer (EORTC) International Antimicrobial Therapy Cooperative Group and the National Cancer Institute of Canada-Clinical Trials Group. J Infect Dis. 1991;163(5):951–8.Google Scholar
  19. 19.
    de Naurois J, et al. Management of febrile neutropenia: ESMO clinical practice guidelines. Ann Oncol. 2010;21(Suppl 5):v252–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Bucaneve G, et al. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Engl J Med. 2005;353(10):977–87.CrossRefPubMedGoogle Scholar
  21. 21.
    Baden LR, et al. Prevention and treatment of cancer-related infections. J Natl Compr Cancer Netw. 2012;10(11):1412–45.CrossRefGoogle Scholar
  22. 22.
    Rangaraj G, et al. Perils of quinolone exposure in cancer patients: breakthrough bacteremia with multidrug-resistant organisms. Cancer. 2010;116(4):967–73.CrossRefPubMedGoogle Scholar
  23. 23.
    Trecarichi EM, Tumbarello M. Antimicrobial-resistant Gram-negative bacteria in febrile neutropenic patients with cancer: current epidemiology and clinical impact. Curr Opin Infect Dis. 2014;27(2):200–10.CrossRefPubMedGoogle Scholar
  24. 24.
    Nguyen AD, et al. A single-center evaluation of the risk for colonization or bacteremia with piperacillin-tazobactam- and cefepime-resistant bacteria in patients with acute leukemia receiving fluoroquinolone prophylaxis. J Oncol Pharm Pract. 2016;22(2):303–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Garnica M, et al. Ciprofloxacin prophylaxis in high risk neutropenic patients: effects on outcomes, antimicrobial therapy and resistance. BMC Infect Dis. 2013;13:356.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Bow EJ. Fluoroquinolones, antimicrobial resistance and neutropenic cancer patients. Curr Opin Infect Dis. 2011;24(6):545–53.CrossRefPubMedGoogle Scholar
  27. 27.
    Wojenski DJ, et al. Cefpodoxime for antimicrobial prophylaxis in neutropenia: a retrospective case series. Clin Ther. 2014;36(6):976–81.CrossRefPubMedGoogle Scholar
  28. 28.
    Klastersky J, 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(16):3038–51.CrossRefPubMedGoogle Scholar
  29. 29.
    Baskaran ND, Gan GG, Adeeba K. Applying the Multinational Association for Supportive Care in Cancer risk scoring in predicting outcome of febrile neutropenia patients in a cohort of patients. Ann Hematol. 2008;87(7):563–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Innes H, et al. Management of febrile neutropenia in solid tumours and lymphomas using the Multinational Association for Supportive Care in Cancer (MASCC) risk index: feasibility and safety in routine clinical practice. Support Care Cancer. 2008;16(5):485–91.CrossRefPubMedGoogle Scholar
  31. 31.
    Uys A, Rapoport BL, Anderson R. Febrile neutropenia: a prospective study to validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score. Support Care Cancer. 2004;12(8):555–60.CrossRefPubMedGoogle Scholar
  32. 32.
    Kern WV, 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(9):1149–56.CrossRefPubMedGoogle Scholar
  33. 33.
    Flowers CR, 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.CrossRefPubMedGoogle Scholar
  34. 34.
    Bodey GP, et al. Fever and infection in leukemic patients: a study of 494 consecutive patients. Cancer. 1978;41(4):1610–22.CrossRefPubMedGoogle Scholar
  35. 35.
    Ortega M, et al. Epidemiology and outcome of bacteraemia in neutropenic patients in a single institution from 1991–2012. Epidemiol Infect. 2015;143(4):734–40.CrossRefPubMedGoogle Scholar
  36. 36.
    Han SB, et al. Clinical characteristics and antibiotic susceptibility of viridans streptococcal bacteremia in children with febrile neutropenia. Infection. 2013;41(5):917–24.CrossRefPubMedGoogle Scholar
  37. 37.
    Han SB, et al. Clinical characteristics and antimicrobial susceptibilities of viridans streptococcal bacteremia during febrile neutropenia in patients with hematologic malignancies: a comparison between adults and children. BMC Infect Dis. 2013;13:273.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Freifeld AG, Razonable RR. Viridans group streptococci in febrile neutropenic cancer patients: what should we fear? Clin Infect Dis. 2014;59(2):231–3.CrossRefPubMedGoogle Scholar
  39. 39.
    Shelburne SA 3rd, et al. Development and validation of a clinical model to predict the presence of beta-lactam resistance in viridans group streptococci causing bacteremia in neutropenic cancer patients. Clin Infect Dis. 2014;59(2):223–30.CrossRefPubMedGoogle Scholar
  40. 40.
    Marron A, et al. High rates of resistance to cephalosporins among viridans-group streptococci causing bacteraemia in neutropenic cancer patients. J Antimicrob Chemother. 2001;47(1):87–91.CrossRefPubMedGoogle Scholar
  41. 41.
    Ford CD, et al. Frequency, risk factors, and outcomes of vancomycin-resistant Enterococcus colonization and infection in patients with newly diagnosed acute leukemia: different patterns in patients with acute myelogenous and acute lymphoblastic leukemia. Infect Control Hosp Epidemiol. 2015;36(1):47–53.CrossRefGoogle Scholar
  42. 42.
    Vigil KJ, et al. Multidrug-resistant Escherichia coli bacteremia in cancer patients. Am J Infect Control. 2009;37(9):741–5.CrossRefPubMedGoogle Scholar
  43. 43.
    Gudiol C, et al. Bacteraemia due to multidrug-resistant Gram-negative bacilli in cancer patients: risk factors, antibiotic therapy and outcomes. J Antimicrob Chemother. 2011;66(3):657–63.CrossRefPubMedGoogle Scholar
  44. 44.
    Gudiol C, et al. Bacteraemia due to extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) in cancer patients: clinical features, risk factors, molecular epidemiology and outcome. J Antimicrob Chemother. 2010;65(2):333–41.CrossRefPubMedGoogle Scholar
  45. 45.
    De Rosa FG, et al. Epidemiology of bloodstream infections in patients with acute myeloid leukemia undergoing levofloxacin prophylaxis. BMC Infect Dis. 2013;13:563.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Sandherr M, et al. Antiviral prophylaxis in patients with solid tumours and haematological malignancies – update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). Ann Hematol. 2015;94(9):1441–50.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Bergmann OJ, et al. Acyclovir given as prophylaxis against oral ulcers in acute myeloid leukaemia: randomised, double blind, placebo controlled trial. BMJ. 1995;310(6988):1169–72.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Aoki T, et al. Efficacy of continuous, daily, oral, ultra-low-dose 200 mg acyclovir to prevent herpes zoster events among bortezomib-treated patients: a report from retrospective study. Jpn J Clin Oncol. 2011;41(7):876–81.CrossRefPubMedGoogle Scholar
  49. 49.
    Pollyea DA, Brown JM, Horning SJ. Utility of influenza vaccination for oncology patients. J Clin Oncol. 2010;28(14):2481–90.CrossRefPubMedGoogle Scholar
  50. 50.
    Safdar A, et al. Dose-related safety and immunogenicity of baculovirus-expressed trivalent influenza vaccine: a double-blind, controlled trial in adult patients with non-Hodgkin B cell lymphoma. J Infect Dis. 2006;194(10):1394–7.CrossRefPubMedGoogle Scholar
  51. 51.
    Takaoka K, et al. A novel scoring system to predict the incidence of invasive fungal disease in salvage chemotherapies for malignant lymphoma. Ann Hematol. 2014;93(10):1637–44.CrossRefPubMedGoogle Scholar
  52. 52.
    Vehreschild JJ, et al. A double-blind trial on prophylactic voriconazole (VRC) or placebo during induction chemotherapy for acute myelogenous leukaemia (AML). J Infect. 2007;55(5):445–9.CrossRefPubMedGoogle Scholar
  53. 53.
    Rotstein C, et al. Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. The Canadian Fluconazole Prophylaxis Study Group. Clin Infect Dis. 1999;28(2):331–40.CrossRefPubMedGoogle Scholar
  54. 54.
    Cornely OA, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007;356(4):348–59.CrossRefPubMedGoogle Scholar
  55. 55.
    Barreto JN, et al. The incidence of invasive fungal infections in neutropenic patients with acute leukemia and myelodysplastic syndromes receiving primary antifungal prophylaxis with voriconazole. Am J Hematol. 2013;88(4):283–8.CrossRefPubMedGoogle Scholar
  56. 56.
    De Pauw B, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46(12):1813–21.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis. 2006;42(10):1417–27.CrossRefPubMedGoogle Scholar
  58. 58.
    Koo S, et al. Diagnostic performance of the (1-->3)-beta-D-glucan assay for invasive fungal disease. Clin Infect Dis. 2009;49(11):1650–9.CrossRefPubMedGoogle Scholar
  59. 59.
    Marty FM, et al. (1->3) beta-D-glucan assay positivity in patients with Pneumocystis (carinii) jiroveci pneumonia. Ann Intern Med. 2007;147(1):70–2.CrossRefPubMedGoogle Scholar
  60. 60.
    Karageorgopoulos DE, et al. Beta-D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis. Clin Infect Dis. 2011;52(6):750–70.CrossRefPubMedGoogle Scholar
  61. 61.
    Fung M, et al. Meta-analysis and cost comparison of empirical versus pre-emptive antifungal strategies in hematologic malignancy patients with high-risk febrile neutropenia. PLoS One. 2015;10(11):e0140930.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Wingard JR, et al. Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. Blood. 2010;116(24):5111–8.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Maschmeyer G, et al. Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Oncol. 2015;26(1):21–33.CrossRefPubMedGoogle Scholar
  64. 64.
    Safdar N, Fine JP, Maki DG. Meta-analysis: methods for diagnosing intravascular device-related bloodstream infection. Ann Intern Med. 2005;142(6):451–66.CrossRefPubMedGoogle Scholar
  65. 65.
    Bow EJ, Meddings JB. Intestinal mucosal dysfunction and infection during remission-induction therapy for acute myeloid leukaemia. Leukemia. 2006;20(12):2087–92.CrossRefPubMedGoogle Scholar
  66. 66.
    Nesher L, Rolston KV. Neutropenic enterocolitis, a growing concern in the era of widespread use of aggressive chemotherapy. Clin Infect Dis. 2013;56(5):711–7.CrossRefPubMedGoogle Scholar
  67. 67.
    Gomez L, Martino R, Rolston KV. Neutropenic enterocolitis: spectrum of the disease and comparison of definite and possible cases. Clin Infect Dis. 1998;27(4):695–9.CrossRefPubMedGoogle Scholar
  68. 68.
    Aksoy DY, et al. Diarrhea in neutropenic patients: a prospective cohort study with emphasis on neutropenic enterocolitis. Ann Oncol. 2007;18(1):183–9.CrossRefPubMedGoogle Scholar
  69. 69.
    Dohner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136–52.CrossRefPubMedGoogle Scholar
  70. 70.
    Faderl S, et al. The biology of chronic myeloid leukemia. N Engl J Med. 1999;341(3):164–72.CrossRefGoogle Scholar
  71. 71.
    Woll PS, et al. Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo. Cancer Cell. 2014;25(6):794–808.CrossRefPubMedGoogle Scholar
  72. 72.
    Pang WW, et al. Hematopoietic stem cell and progenitor cell mechanisms in myelodysplastic syndromes. Proc Natl Acad Sci U S A. 2013;110(8):3011–6.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Papaemmanuil E, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616–27. quiz 3699CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Ravandi F, O'Brien S. Immune defects in patients with chronic lymphocytic leukemia. Cancer Immunol Immunother. 2006;55(2):197–209.CrossRefPubMedGoogle Scholar
  75. 75.
    Freeman JA, et al. Immunoglobulin G subclass deficiency and infection risk in 150 patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2013;54(1):99–104.CrossRefPubMedGoogle Scholar
  76. 76.
    Hamblin AD, Hamblin TJ. The immunodeficiency of chronic lymphocytic leukaemia. Br Med Bull. 2008;87:49–62.CrossRefPubMedGoogle Scholar
  77. 77.
    Abkur TM, et al. Pneumocystis jiroveci prophylaxis in patients undergoing Bendamustine treatment: the need for a standardized protocol. Clin Case Rep. 2015;3(4):255–9.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Morrison VA. Infectious complications in patients with chronic lymphocytic leukemia: pathogenesis, spectrum of infection, and approaches to prophylaxis. Clin Lymphoma Myeloma. 2009;9(5):365–70.CrossRefPubMedGoogle Scholar
  79. 79.
    Morrison VA. Management of infectious complications in patients with chronic lymphocytic leukemia. Hematol Am Soc Hematol Educ Program. 2007:332–8.CrossRefGoogle Scholar
  80. 80.
    Nucci M, Anaissie E. Infections in patients with multiple myeloma in the era of high-dose therapy and novel agents. Clin Infect Dis. 2009;49(8):1211–25.CrossRefPubMedGoogle Scholar
  81. 81.
    Costa DB, Shin B, Cooper DL. Pneumococcemia as the presenting feature of multiple myeloma. Am J Hematol. 2004;77(3):277–81.CrossRefPubMedGoogle Scholar
  82. 82.
    Lanini S, et al. Risk of infection in patients with lymphoma receiving rituximab: systematic review and meta-analysis. BMC Med. 2011;9:36.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Martin SI, et al. Infectious complications associated with alemtuzumab use for lymphoproliferative disorders. Clin Infect Dis. 2006;43(1):16–24.CrossRefPubMedGoogle Scholar
  84. 84.
    Scappaticci FA, et al. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol. 2005;91(3):173–80.CrossRefPubMedGoogle Scholar
  85. 85.
    Eveno C, et al. Bevacizumab doubles the early postoperative complication rate after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. 2014;21(6):1792–800.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Internal Medicine, Division of Infectious DiseasesUniversity of Nebraska Medical CenterOmahaUSA

Personalised recommendations