Who hesitate and falter life away,

And lose tomorrow the ground won today.

MATTHEW ARNOLD

The Scholar Gypsy, 1853

Neutropenia is the major risk factor for serious bacterial and fungal infections in cancer patients following myelosuppressive chemotherapy.<sup>9 Bodey G.P., Buckley M., Sathe Y.S. , e al. Quantitative relationships between circulating leukocytes and infections in patients with acute leukemia Ann Intern Med 1966 ;  64 : 328

Cliccare qui per andare alla sezione Riferimenti, 81 Pizzo P.A. Management of fever in patients with cancer and treatment-induced neutropenia N Engl J Med 1993 ;  328 : 1323  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> Despite the progress made in supportive care of febrile neutropenic patients, including broad-spectrum antimicrobial agents and hematopoietic growth factors, neutropenia remains the major reason for hospitalization during or after chemotherapy.<sup>81 Pizzo P.A. Management of fever in patients with cancer and treatment-induced neutropenia N Engl J Med 1993 ;  328 : 1323  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> It is also a significant risk factor for infection in organ and marrow transplantation and for patients with bone-marrow failure.

The timely use of antibacterial agents, initiated at the first sign of fever in the neutropenic cancer patient, has dramatically reduced infection-related morbidity and mortality.<sup>72 Pizzo P.A. Granulocytopenia and cancer therapy: Past problems, current solutions, future challenges Cancer 1984 ;  54 : 2649  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 95 Schimpff S. Overview of empiric antibiotic therapy for the febrile, neutropenic patient Rev Infect Dis 1985 ;  7 : 573

Cliccare qui per andare alla sezione Riferimenti</sup> Despite appropriate interventions, 5% to 10% of cancer patients still succumb to infectious complications associated with neutropenia.<sup>25 De Pauw B., Deresinski S., Feld R. , e al. Ceftazidime compared with piperacillin and tobramycin for the empiric treatment of fever in neutropenic patients with cancer Am J Med 1994 ;  120 : 834

Cliccare qui per andare alla sezione Riferimenti, 36 Freifeld A., Walsh T., Marshall D. , e al. Monotherapy for fever and neutropenia in cancer patients: A randomized comparison of ceftazidime versus imipenem J Clin Oncol 1995 ;  13 : 165

Cliccare qui per andare alla sezione Riferimenti, 82 Pizzo P.A., Hathorn J.W., Hiemenz J. , e al. A randomized trial comparing ceftazidime alone with combination antibiotic therapy in cancer patients with fever and neutropenia N Engl J Med 1986 ;  315 : 552  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> Although most deaths now occur in patients with prolonged neutropenia, the risk of complications is high if antimicrobial therapy is delayed. Therefore, it is important to consider the febrile neutropenic patient as a medical emergency requiring immediate diagnostic and therapeutic interventions. Even in febrile neutropenic patients with a noncancer underlying condition the urgency of evaluation and treatment cannot be overstated. Although uncommon, neutropenic patients can have a serious infection in the absence of fever.<sup>84 Pizzo P.A., Robichaud K.J., Wesley R. , e al. Fever in the pediatric and young adult patient with cancer. A prospective study of 1001 episodes Medicine 1982 ;  61 : 153

Cliccare qui per andare alla sezione Riferimenti, 97 Sickles E.A., Greene W.H., Wiernik P.H. Clinical presentation of infection in granulocytopenic patients Arch Intern Med 1975 ;  135 : 715

Cliccare qui per andare alla sezione Riferimenti</sup> Thus, signs or symptoms compatible with infection in the neutropenic patient, regardless of the presence of fever, warrant prompt attention.

The importance of an adequate number of functioning neutrophils in antimicrobial activity has been appreciated for many years. At the turn of the century, Metchnikoff noted that the absence of what we now know as granulocytes could result in failure to control infections. Prior to the use of myelosuppressive chemotherapy, rare patients with congenital agranulocytosis or an acquired neutropenia were noted to suffer recurrent bacterial infections, especially of the skin and sinopulmonary tract. Similarly, bone marrow–failure patients frequently succumbed to bacterial or fungal infections, often despite intervention with antimicrobial agents.<sup>108 Weinberger M. Approach to management of fever and infection in patients with primary bone marrow failure and hemoglobinopathies Hematol Oncol Clin North Am 1993 ;  7 : 865

Cliccare qui per andare alla sezione Riferimenti</sup> In both of these populations, the predisposition to infection was ascribed to the absence of circulating neutrophils. The modern approach to the management of febrile neutropenic cancer patients has been successfully applied to these and other populations, including solid organ–transplant recipients, patients with acquired or intrinsic neutropenia, and HIV-infected individuals. Other factors contributing to the overall state of immunosuppression, however, are important determinants of infectious risk. In this regard, not all patients with neutropenia are identical.

This article addresses the foundations for the evolution of empiric therapy in the febrile neutropenic cancer patient, attempts to clarify how and in what way these principles can be adapted to different neutropenic hosts, and addresses the problems associated with neutropenia that result from a serious infection.