THERAPEUTIC MONITORING OF EXPERIMENTAL INVASIVE PULMONARY ASPERGILLOSIS BY ULTRAFAST COMPUTERIZED-TOMOGRAPHY, A NOVEL, NONINVASIVE METHOD FOR MEASURING RESPONSES TO ANTIFUNGAL THERAPY

Pulmonary infiltrates in neutropenic hosts with invasive aspergillosis are due to vascular invasion and hemorrhagic infarction. In order to measure the effect of antifungal compounds on this organism-mediated t issue injury, we monitored the course of pulmonary infiltrates by seri al ultrafast computerized tomography (UFCT) in persistently granulocyt openic rabbits with experimental invasive pulmonary aspergillosis. The course of pulmonary lesions measured by serial UFCT scans was compare d with those measured by conventional chest radiography, histopatholog ical resolution of lesions, and microbiological clearance of Aspergill us fumigatus. Treatment groups included either amphotericin B colloida l dispersion in dosages of 1, 5, and 10 mg/kg of body weight per day i ntravenously or conventional desoxycholate amphotericin B at 1 mg/kg/d ay intravenously, Therapeutic monitoring of pulmonary lesions by UFCT demonstrated a significant dose-response relationship. Lesions continu ed to progress in untreated controls, whereas lesions in treated rabbi ts initially increased and then decreased in response to antifungal th erapy in a dosage-dependent manner (P less than or equal to 0.05 to P less than or equal to 0.005, depending upon the groups compared). This same trend of resolution of lesions in response to antifungal therapy was also demonstrated by postmortem examination and by microbiologica l clearance of the organism. These data indicated that amphotericin B colloidal dispersion at 5 and 10 mg/kg/day exerted a more rapid rate o f clearance of lesions than conventional amphotericin B. UFCT was more sensitive than conventional chest radiography in detecting lesions du e to invasive pulmonary aspergillosis (P < 0.05 to P < 0.005, dependin g upon the groups compared). These findings establish a correlation am ong UFCT-defined lesions, microbiological response, and resolution of pathologically defined lesions in experimental invasive pulmonary aspe rgillosis. Serial monitoring of UFCT-defined lesions of aspergillosis provides a novel system for determining the antifungal response of org anism-mediated tissue injury.