The phagocytic system, along with the physical integument, represents the first line of defense against infecting microorganisms. The neutrophil or polymorphonuclear cell is the predominate cell of the phagocytic system.

Neutrophil dysfunction can manifest itself either by quantitative or qualitative defects. Quantitative defects are seen most commonly, and these are classified as hereditary or acquired.
Qualitative defects are divided into defects in microbicidal activity or those involving cell migration.

Quantitative neutropenia is stratified by the extent of neutropenia. An absolute neutrophil count (ANC) of 1,000 or fewer metamyelocytes, band forms, and neutrophils per microliter is considered significant neutropenia; an ANC of 100 or fewer per microliter is considered profound neutropenia.

The etiology of neutropenias commonly is classified as functional deficits or neutropenia secondary to an etiologic factor. Functional classifications of neutropenias include (a) disorders of proliferation of committed stem cells (e.g., cyclic neutropenia, reticular dysgenesis); (b) disorders of committed myeloid stem cells (e.g., infantile genetic agranulocytosis of Kostmann, acquired neutropenias); (c) disorders associated with immune dysfunctions or metabolic disturbances (e.g., cartilage hair hypoplasia, metabolic disorders); and (d) disorders associated with decreased neutrophil survival (e.g., immune neutropenias, viral infections).

The acquired neutropenias are associated most commonly with disorders of committed myeloid stem cells. Causes include infections (Box 137.1), drugs (e.g., antibiotics such as trimethoprim-sulfamethoxazole, penicillin; anticonvulsants such as phenytoin; barbiturates; and other miscellaneous drugs such as thiazides and propranolol), chemical and environmental toxins (e.g., benzene, DDT), anticancer chemotherapy (e.g., doxorubicin [Adriamycin], methotrexate, cytosine arabinoside), and infiltration of bone marrow (e.g., leukemia, lymphoma, neuroblastoma).

Because of the increasing and intensive use of chemotherapeutic agents in patients with cancer, this patient population
has become a paradigm for patients with neutropenia and presumed infection. The infecting organisms for this patient population are the gram-positive bacteria, primarily Staphylococcus epidermidis, Staphylococcus aureus, and viridans streptococci (Table 137.2). Corynebacterium jeikeium is associated with catheter-related infections. Of the gram-negative bacteria, Enterobacter species can be problematic because they easily induce beta-lactamase, rendering these organisms resistant to the cephalosporins and penicillin. Fungal infections occur most commonly in patients with prolonged neutropenia on broad-spectrum antibiotics. The predominate fungal organisms are Candida species, emanating from the patients’ own gastrointestinal tract, and Aspergillus species, acquired from the respiratory route.