Prophylaxis of bacterial infections with oral antibiotics in neutropenic patients. Lessons from the last two EORTC trials and prospects for the future.

It is well known that patients with granulocytopenia due either to bone marrow failure, acute leukemia or its treatment, or as a result of other intensive chemotherapy are at enhanced risk of serious infection. Several approaches have been designed to minimize the risk of infection in these patients by means of suppression of gastrointestinal flora. A retrospective review of infection in febrile neutropenic patients revealed a significant decrease in bacteremia in patients who had received some oral antimicrobial regimen compared with those who did not. In one large series, infection due to the four most common infecting organisms in neutropenic patients (Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Klebsiella species) occurred in 28% of 380 patients receiving some oral antibiotic regimen compared with 44% of 426 receiving no oral prophylaxis. Aminoglycosides alone or in combination with vancomycin or polymyxin and bacitracin and other agents have been utilized in gut decontaminating regimens. More recently, selective decontamination with a variety of oral agents including nalidixic acid, cotrimoxazole, colistin, etc. have been shown to be effective in some trials. Although cotrimoxazole initially was thought to be beneficial in reducing infection and bacteremia in neutropenic patients, the recently completed EORTC trial did not show a significant difference in incidence of infection or bacteremia in acute leukemia patients attendant upon the use of oral trimethoprim-sulfamethoxazole. There was a significant reduction in infections and bacteremia in patients with malignancies other than acute non-lymphocytic leukemia. Thus, there is a need for infection prevention in neutropenic patients but the optimal method for achieving this goal remains to be determined.