[Prevention and treatment of febrile neutropenia]

Many chemotherapy regimens are associated with variable periods of myelosuppression. In cancer patients, neutropenia (less than 500 neutrophils/microL) is the most important risk factor for infections. The incidence and severity of infectious complications are related to depth and duration of neutropenia, with the highest risk if neutrophils are less than 100/microL for more than a week. The period required for neutrophil recovery is usually short with standard regimens, but prolonged after high dose chemotherapy followed by autologous bone marrow transplant (-ABMT) or peripheral blood stem cell (PBSC) infusion. Under these conditions, the administration of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) accelerates neutrophil recovery and shortens the duration of hospitalization. In standard chemotherapy settings, prophylactic use of CSF's is a matter of debate. Several studies have reached contrasting conclusion, but, combining effectiveness and costs, it results that this use of CSF'S is not to be recommended unless the risk of infections (elderly patients, reduced marrow reserve) is high. The administration of G-CSF or GM-CSF to a febrile neutropenic patient (cfr CSF's therapy) shortens the duration of neutropenia, although no great clinical benefits are evident. Nevertheless the identification of subsets of patients with additional risk factors (i.e. absolute neutrophil count < 100/microL at the onset of fever or delayed neutrophil recovery) should be helpful in establishing the role of CSF's therapy. When prolonged periods of severe neutropenia (less than 500 neutrophils/microL) are expected, antibiotics should be prophylactically administered. Fluoroquinolones seem to be the optimal choice in heavily myelosuppressed patients (ie. bone marrow transplant recipients). Fluoroquinolones are effective in reducing the frequency of gram-negative bacteremia, but, because of incomplete coverage, gram-positive infections are becoming increasingly problematic. The association with an agent that can be absorbed orally, active against gram-positive cocci, seems to be an effective strategy. Fungal infections are an important cause of morbility and mortality in severely neutropenic patients. Safety and efficacy of antifungal triazoles and the lipid formulations of amphotericin B used prophylactically still require investigation. In patients at high risk for fungal infections, monitoring cultures are predictive for systemic mycoses and should guide prophylactic and therapeutic choices. The standard treatment of oncologic patients with potential infectious neutropenia complications is admission to the hospital and treatment with broad-spectrum intravenous antibiotics. Until third generation cephalosporin and carbapenems became available, most neutropenic febrile patients were treated with associations of an aminoglycoside plus a beta-lactam. Monotherapy with the new antibiotics has proven to be effective as an association therapy and offers advantages in terms of cost and tolerability. Whether or not vancomycin is included in the initial antibiotic regimen should be decided on the basis of epidemiological consideration (i.e. prevalence of meticillin-resistant Staphylococcus aureus or Staphylococcus mitis in certain centers). Antifungal therapy is indicated in neutropenic patients who remain febrile after one week of broad-spectrum antibiotics or have recurrent fever. Amphotericin B should be promptly administered in patients suspected of invasive mycoses. Selected patients with fever and neutropenia, that can be identified on the basis of reduced risk of severe complications, do not need hospitalization. In the first reports, outpatient treatment has proven to be effective, cost saving and well received by patients, but further studies are needed to accurately define low risk status and the optimal home antibiotic regimens.