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Infection is the most common complication associated with neutropenia (1). Bacterial infections occur early, whereas most fungal and some viral infections are more common in patients with persistent neutropenia (2). The spectrum of infection is influenced by several factors, including the nature and intensity of chemotherapy, antimicrobial prophylaxis, and the use of catheters and other medical devices (3,4). Febrile neutropenic patients are a heterogeneous group. Risk prediction rules have been developed that can reliably identify a "low-risk" subset among febrile neutropenic patients (5,6). The administration of prompt broad-spectrum parenteral antibiotic therapy to a neutropenic patient who becomes febrile is the accepted standard of care (7). Oral and parenteral outpatient regimens represent new options in the management of "low-risk" febrile neutropenic patients (8). Antimicrobial prophylaxis is useful for preventing infections in high-risk patients. Hematopoetic growth factors and granulocyte transfusions are useful in refractory infections. All these issues are discussed in this chapter, with an emphasis on strategies that have been developed at the University of Texas MD Anderson Cancer Center.

Fever is defined as a single temperature ≥ 38.3°C (101°F). Some neutropenic patients may be unable to mount an adequate inflammatory response and may be afebrile or even hypothermic when infected. Neutropenia is defined as an absolute neutrophil count (ANC) of ≤ 500/mm3, although the risk of infection begins to increase as the ANC falls below 1000/mm3 (7,9).

The epidemiology of bacterial infections in neutropenic cancer patients undergoes periodic changes, and it is important to conduct epidemiologic surveys in order to detect these changes in a timely manner (Fig. 43-1). Currently, in approximately 50% of febrile neutropenic patients no clinical site of infection (eg, cellulitis, pneumonia) is identified, and all microbiological cultures are negative (Fig. 43-2). These are referred to as episodes of unexplained fever and probably represent low-grade or undetectable infection (2). The most common sites of infection include the respiratory tract, urinary tract, bloodstream, gastrointestinal tract, and skin/skin structure infections (Fig. 43-3) (4).

Figure 43-1.

Changing epidemiology of bacterial infections in patients with cancer (1994-2009).

Figure 43-2.

Nature of febrile episodes in neutropenic patients.

Figure 43-3.

Breakdown of microbiologically documented infections in neutropenic patients.

Gram-positive organisms are the most frequent cause of bloodstream infections in neutropenic patients (3,10). Bloodstream infections however, account for only 20 to 35% of documented infections. Infections at most other sites are caused more often by gram-negative bacilli and are frequently polymicrobial (see Fig. 43-4) (11). The most common fungal organisms causing infections ...

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