Empiric antifungal therapy in febrile granulocytopenic patients. EORTC International Antimicrobial Therapy Cooperative Group.
OBJECTIVE
The optimal management of fever in granulocytopenic patients remains controversial. Invasive fungal infections are common and life-threatening but are difficult to diagnose early. In this randomized study, we investigated the potential value of empiric administration of amphotericin B (versus no empiric antifungal therapy) in 132 patients remaining febrile and granulocytopenic despite broad-spectrum antibiotic therapy for four days.


METHODS
The patients were divided into two groups: 68 who were randomly assigned to receive empiric amphotericin B, and 64 who were randomly assigned to continue only the protocol antibiotics that they were already receiving. Amphotericin B was administered intravenously as follows: every other day at a dose of 1.2 mg/kg body weight or daily at a dose of 0.6 mg/kg body weight. Clinical response was evaluated as success or failure, depending upon the febrile course after randomization.


RESULTS
Based on the evolution of fever, the response rate was 69% in the group of patients receiving empiric amphotericin B and 53% for the other group (p = 0.09). There were six documented (four severe) fungal infections in 64 patients randomized not to receive the antifungal therapy as compared to only one fungemia among 68 patients treated empirically with amphotericin B (p = 0.1). No deaths due to fungal infection occurred among the patients receiving empiric amphotericin B compared to four in the other group (p = 0.05). However, this study did not demonstrate a difference in survival between the two groups of patients (with or without empiric amphotericin B). The benefit of empiric administration of amphotericin B was primarily observed in specific subgroups of patients, such as those who did not receive any antifungal prophylaxis (78% versus 45%, p = 0.04), those who were severely granulocytopenic (69% versus 46%, p = 0.06), febrile patients with a clinically documented infection (75% versus 41%, p = 0.03), and patients older than 15 years of age (67% versus 47%, p = 0.06).


CONCLUSIONS
These data suggest a benefit for early amphotericin B treatment in granulocytopenic patients with continued fever despite antibiotic therapy.
D000380:Agranulocytosis / Q000188:drug therapy* / Q000209:etiology; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D005334:Fever / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007262:Infusions, Intravenous; D015337:Multicenter Studies as Topic; D009181:Mycoses / Q000150:complications / Q000188:drug therapy*; D009369:Neoplasms / Q000150:complications; D011897:Random Allocation; D012044:Regression Analysis; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000666:Amphotericin B