PREVENTION AND TREATMENT OF FEBRILE NEUTR OPENIA

Many chemotherapy regimens are associated with variable periods of mye losuppression. In cancer patients, neutropenia (less than 500 neutroph ils/mu L) is the most important risk factor for infections. The incide nce and severity of infectious complications are related to depth and duration of neutropenia, with the highest risk if neutrophils are less than 100/mu L for more than a week. The period required for neutrophi l recovery is usually short with standard regimens, but prolonged afte r high dose chemotherapy followed by autologous bone marrow transplant (ABMT) or peripheral blood stem cell (PBSC) infusion. Under these con ditions, the administration of granulocyte colony-stimulating factor ( G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) ac celerates neutrophil recovery and shortens the duration of hospitaliza tion. In standard chemotherapy settings, prophylactic use of CSF's is a matter of debate. Several studies have reached contrasting conclusio n, 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-CS F or GM-CSF to a febrile neutropenic patient (cfr CSF's therapy) short ens the duration of neutropenia, although no great clinical benefits a re evident. Nevertheless the identification of subsets of patients wit h additional risk factors (i.e. absolute neutrophil count <100/mu L at the onset of fever or delayed neutrophil recovery) should be helpful in establishing the role of CSF's therapy. When prolonged periods of s evere neutropenia (less than 500 neutrophils/mu L) are expected, antib iotics should be prophylactically administered. Fluoroquinolones seem to be the optimal choice in heavily myelosuppressed patients (ie. bone marrow transplant recipients). Fluoroquinolones are effective in redu cing the frequency of gram-negative bacteremia, but, because of incomp lete coverage, gram-positive infections are becoming increasingly prob lematic. The association with an agent that can be absorbed orally, ac tive against gram-positive cocci, seems to be an effective strategy. F ungal infections are an important cause of morbility and mortality in severely neutropenic patients. Safety and efficacy of antifungal triaz oles and the lipid formulations of amphotericin B used prophylacticall y still require investigation. In patients at high risk for fungal inf ections, monitoring cultures are predictive for systemic mycoses and s hould guide prophylactic and therapeutic choices. The standard treatme nt of oncologic patients with potential infectious neutropenia complic ations is admission to the hospital and treatment with broad-spectrum intravenous antibiotics. Until third generation cephalosporin and carb apenems became available, most neutropenic febrile patients were treat ed with associations of an aminoglycoside plus a betalactam. Monothera py with the new antibiotics has proven to be effective as an associati on therapy and offers advantages in therms of cost and tolerability. W hether or not vancomycin is included in the initial antibiotic regimen should be decided on the basis of epidemiological consideration (i.e. prevalence of meticillin-resistent Staphylococcus aureus or Staphyloc occus mitis in certain centers). Antifungal therapy is indicated in ne utropenic patients who remain febrile after one week of broad-spectrum antibiotics or have recurrent fever. Amphotericin B should be promptl y administered in patients suspected of invasive mycoses. Selected pat ients 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 nee ded to accurately define low risk status and the optimal home antibiot ic regimens.