Early versus delayed initiation of amphotericin B deoxycholate in the empiric treatment of persistent neutropenic fever

INTERVENTION: Initiation of amphotericin B deoxycholate on day 4 (early initiation or treatment A) . Fourth day of fever (38.3 degrees Celsius or more), i.e., persistent fever (i.e., despite being treated with broad‐spectrum antibiotics). Administration method: First, these patients will receive 1 L of normal saline (NaCl 0.9%) intravenously for 1 hour. Then, they will receive 1 L of 5% dextrose in water (D5W) plus 1 mg/kg daily of amphotericin B deoxycholate plus one vial (10 mL) of Multiple Vitamins for Infusion (Dextrevit Registered Trademark) given by slow infusion (12 hours). The 12‐hour infusion is a combination of the D5W, amphotericin B deoxycholate and Multiple Vitamins, which are all given once daily. Amphotericin B deoxycholate will continue for at least 48 hours after the patient is afebrile and his absolute neutrophil count is 500 cells/mm3 or more. The latter decision will be made by the research team. A team member will also monitor adherence on a daily basis. CONDITION: Persistent neutropenic fever PRIMARY OUTCOME: Difference in time for fever resolution. ; This outcome will be assessed using a mercury thermometer. SECONDARY OUTCOME: Difference in hepatotoxicity. ; This outcome will be assessed by liver function tests, and it is defined as an increase of at least three times the transaminases' baseline level. Difference in hypokalemia. ; This outcome will be assessed by serum potassium, and it is defined as a serum potassium level of less than 3.5 mEq/L. Difference in hypomagnesemia. ; This outcome will be assessed by serum magnesium, and it is defined as a serum magnesium level of less than 1.5 mEq/L. Difference in inhospital mortality. ; This outcome will be assessed by reviewing medical records. Difference in length of stay. ; This outcome will be assessed by reviewing medical records. Difference in mortality due to invasive mycoses. ; This outcome will be assessed by reviewing medical records. ; Considering this outcome, the diagnostic information included in the medical records will be CT reports, biopsy material, galactomannan assays, and the like. Difference in nephrotoxicity. ; This outcome will be assessed by serum creatinine, and it is defined as a relative increase in serum creatinine 2‐fold or more over baseline and/or an absolute increase of 0.5 mg/dL or more above baseline. INCLUSION CRITERIA: 1. Neutropenic fever, 2. High‐risk patient, 3. Persistent fever, 4. No source of infection at the time of randomization.