PROPHYLACTIC USE OF ITRACONAZOLE FOR THE PREVENTION OF INVASIVE PULMONARY ASPERGILLOSIS IN HIGH-RISK NEUTROPENIC PATIENTS

Invasive pulmonary aspergillosis (IPA) is an increasing cause of morbi dity and mortality in patients with hematologic malignancies. A major program of construction work close to our unit prompted us to evaluate thee efficacy of itraconazole prophylaxis in preventing IPA in these patients. During September 1994 to December 1995, 77 patients undergoi ng 96 neutropenic episodes (mean duration, 19.3 days +/- 9.1) received itraconazole as antifungal prophylaxis. All patients were treated in laminar air flow rooms. Itraconazole was administered at a loading dos e of 600mg/d, (day1 to day3) and 400mg/d on the following days, in 87 instances. In the remaining episodes, the daily dose was 200 or 400mg. Oral doses were adjusted to reach a plasma itraconazole level (PIL) a bove 1000ng/l. In cases of inadequate Pa or poor oral intake, IV Ampho B was started at a 20 mg daily dose. Five cases of IPA (proven n = 2, probable n = 3) were observed. This represents an incidence of 5.2% of the total number of episodes. One out of 67 (2%) treatment episodes w ith adequate PIL, were associated with IPA as compared to 4 of 29 (14% ) episodes with inadequate PIL, (p < 0.02). AmphoB was added in 28 cas es because of low PIL (n = 25), and/or antibiotic-resistant fever pers istent pulmonary infiltrate (n = 8). These results need to be interpre ted with caution, because of the absence of randomization or a control group. The efficacy of Itraconazole in neutropenic patients with high risk IPA has to be confirmed on larger and prospective studies.