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Background: Amphotericin B deoxycholate is currently the standard empirical antifungal therapy in neutropenic patients with cancer who have persistent fever that does not respond to antibiotic therapy. However, this treatment often causes infusion-related and metabolic toxicities, which may be dose limiting. Objective: To compare the efficacy and safety of itraconazole with those of amphotericin B as empirical antifungal therapy. Design: An open randomized, controlled, multicenter trial, powered for equivalence. Setting: 60 oncology centers in 10 countries. Patients: 384 neutropenic patients with cancer who had persistent fever that did not respond to antibiotic therapy. Intervention: Intravenous amphotericin B or intravenous itraconazole followed by oral itraconazole solution. Measurements: Defervescence, breakthrough fungal infection, drug-related adverse events, and death. Results: For itraconazole and amphotericin B, the median duration of therapy was 8.5 and 7 days and the median time to defervescence was 7 and 6 days, respectively. The intention-to-treat efficacy analysis of data from 360 patients showed response rates of 47% and 38% for itraconazole and amphotericin B, respectively (difference, 9.0 percentage points [95% CI, -0.8 to 19.5 percentage points]). Fewer drug-related adverse events occurred in the itraconazole group than the amphotericin B group (5% vs. 54% of patients; P=0.001), and the rate of withdrawal because of toxicity was significantly lower with itraconazole (19% vs. 38%; P=0.001). Significantly more amphotericin B recipients had nephrotoxicity (P Conclusions: Itraconazole and amphotericin B have at least equivalent efficacy as empirical antifungal therapy in neutropenic patients with cancer. However, itraconazole is associated with significantly less toxicity.

Objective: To determine whether augmented quinolone-based antibacterial prophylaxis in neutropenic patients with cancer reduces infections caused by gram positive cocci and preserves the protective effect against aerobic gram-negative bacilli. Design: Open, randomized, controlled, multicenter clinical trial. Setting: Centers participating in the National Cancer Institute of Canada Clinical Trials Group. Patients: 111 eligible and evaluable patients hospitalized for severe neutropenia (neutrophil count < 0.5 x 109/L lasting at least 14 days) who were receiving cytotoxic therapy for acute leukemia or bone marrow autografting. Intervention: One of three oral antibacterial prophylactic regimens (norfloxacin, 400 mg every 12 hours; ofloxacin, 400 mg every 12 hours; or ofloxacin, 400 mg, plus rifampin, 300 mg every 12 hours) beginning with cytotoxic therapy. Measurements: Incidence and cause of suspected or proven infection. Results: Microbiologically documented overall infection rates for norfloxacin, ofloxacin, and ofloxacin plus rifampin were 47%, 24%, and 9%, respectively (P < 0.001). Corresponding rates were 24%, 13%, and 3%, respectively for staphylococcal bacteremia (P= 0.03) and, 21%, 3%, and 3%, respectively for streptococcal bacteremia (P< 0.01). The pattern of bacteremia suggested that rifampin played a role in suppressing staphylococcal infection. Both ofloxacin alone and ofloxacin plus rifampin had a clinically significant antistreptococcal effect. Aerobic gram-negative rods were cleared from rectal surveillance cultures in all patients after a median of 5.5 days and caused infection in only one patient (0.9%). The reductions in the number of microbiologically documented infections among ofloxacin recipients and ofloxacin plus rifampin recipients were offset by concomitant increases in the number of unexplained fevers (24% of norflaxacin recipients, 53% of ofloxacin recipients, and 49% of ofloxacin plus rifampin recipients; P = 0.02). No statistically significant difference was found among the treatment arms with respect to the overall incidence of febrile neutropenic episodes as defined for this trial (79% for the norfloxacin group, 82% for the ofloxacin group, and 77% for the oflaxacin plus rifampin group). Conclusions: Quinolone-based antibacterial chemoprophylaxis protected patients from aerobic gram-negative bacillary infections. Augmentation of the gram-positive activity reduced the incidence of gram-positive infections but did not influence the overall incidence of febrile neutropenic episodes., The addition of the drug rifampin to quinolone antibiotic treatment appears to reduce the incidence of streptococcal infections in patients with low white blood cell counts. Doctors randomly assigned 111 patients with low white blood cell counts to take either norfloxacin, ofloxacin, or ofloxacin plus rifampin. Fewer patients taking ofloxacin plus rifampin developed infections (9%) than those taking ofloxacin alone (24%) or norfloxacin alone (47%). There was no significant difference in the number of fever episodes among the three treatment groups.