Growth Factors and Empiric Therapy with Antibiotics: Should They Be Used Concurrently?

Two colony-stimulating factors—or hematopoietic growth factors—are commercially available: human recombinant granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). These compounds are used frequently by oncologists to reduce the nadir of chemotherapy-induced neutropenia or hasten the recovery of normal neutrophil counts after chemotherapy in the hope that infection will not develop or that febrile neutropenia will quickly resolve. Based on current knowledge, what should be the rational use of these cytokines?

Aggressive chemotherapy with or without total body radiation leads to leukopenia, among other side effects. Infection is the major consequence of neutropenia. Infection incidence and severity have an inverse relation to the granulocyte count and to its rate of decrease. Most infections (and nearly all severe infections) and bacteremias develop when the granulocyte count is less than 0.1 × 10⁹/L (<100/µL). Most severe infections (about 85%) are caused by three gram-positive cocci (α-hemolytic streptococcal species, Staphylococcus epidermidis, and Staphylococcus aureus), three gram-negative rods (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa), and two types of fungi (Candida species, especially albicans and tropicalis, and Aspergillus species, especially flavus and fumigatus). Today, gram-positive infections tend to be more common than gram-negative infections, and Pseudomonas aeruginosa infections have become infrequent at many centers. Gram-negative bacillary and streptococcal bacteremias in this setting often lead to rapid death if not treated immediately. Fungal infections are more likely to develop after prolonged periods of neutropenia and antibiotic-induced alterations of alimentary canal and respiratory tract flora [1].

Much effort has been spent attempting to prevent infections during neutropenic episodes. It is convenient to divide these approaches into four major categories. The first is to avoid invasive procedures wherever possible, such as being exquisitely careful about the care of an indwelling venous catheter. The second approach is to prevent new potential …