Patients receiving chemotherapy are at high risk for developing neutropenia and severe infections when their neutrophil count is depressed. Neutropenia is defined as an absolute neutrophil count (ANC) of ≤500 cells/mm3. The term “profound neutropenia” is often used to describe an ANC <100 cells/mm3. Fever in the neutropenic patient is defined as a single temperature of >38.3°C or a temperature of >38.0°C over at least 1 hour. Given the lack of inflammatory cells associated with neutropenia, signs of infection may be subtle. Skin and soft-tissue infections may lack the typical induration, erythema, and warmth often seen in patients with an intact immune system. A pulmonary infection may have only a subtle infiltrate on chest radiography and cerebrospinal fluid pleocytosis may be modest or absent despite ongoing meningitis. Some patients may not mount a fever at all and the presence of hypotension, tachycardia, or delirium may be the only presenting features of infection.

Several approaches have been developed to address the clinical entity of fever and neutropenia. Some research has looked at preventing neutropenia with the use of colony-stimulating factors. Other research has focused on preventing infection in the neutropenic patient; still others have looked at the empiric use of antimicrobials to treat infections when fever occurs. In this chapter, we focus on these three approaches as well as the main causes of infections in these severely immunocompromised individuals.