Combination Antifungals for Treatment of Pulmonary Invasive Aspergillosis (IA) Refractory to Amphotericin B (AmB) in Leukaemia Patients

T. GENTINA1, S. DE BOTTON 1, S. ALFANDARI 2, J. DELOMEZ 3, S. JAILLARD 4, O. LEROY 2, C. MARQUETTE 5, G. BEAUCAIRE 2, F. BAUTERS 1, P. FENAUX 1

Author address: 

1Service des Maladies du Sang, CHRU, Lille, France, 2Service de Reanimation et Maladies Infectieuses, Tourcoing, France, 3Service de Radiologie, Lille, France, 4Service de Chirurgie Thoracique, Lille, France, 5Clinique des Maladies Respiratoires, Li

Abstract: 

Background: IA has a high mortality rate in leukemia patients with profound and prolonged neutropenia when treated with AmB alone. Recently, two antifungal drugs, voriconazole (V) and caspofungin (C), have been developed. We evaluated, in IA refractory to AmB, iv antifungal therapies combining C (70 mg on D1, followed by 50 mg/d) with V (200 mg b.i.d) or liposomal AmB (L-amB) (5 mg/kg/d). Methods: From 8/2001 to 3/2002, 6 leukemia patients with IA refractory to therapy with AmB (L-amB n = 5; AmB colloidal dispersion n = 1) received combination therapy including C with L-AmB (n = 4) or V (n = 2). Results: Combination therapies were started 8 days after initial IA diagnosis. Duration of neutropenia after initiation of combination therapy ranged 4 to 25 days. Based on CT scan, broncho-alveolar lavage and histopathology, IA was classified as definite in 3 cases and probable in 3 cases. All patients had pulmonary IA, including one with disseminated IA (cerebral, thyroid, ocular and pulmonary). In all patients, sequential CT-scans, demonstrated improvement with a rapid reduction of the size of lesions. Additional surgery was only required in 2 cases. Improvement allowed administration of consolidation chemotherapy in 3 patients without recurrence of IA. Median duration of combination therapy was 62 days (range 42-107). During antifungal therapy, 3 patients died. None of those deaths were related to IA. No toxicity of antifungal therapy was observed. Conclusion: Combination antifungal therapy of IA with C, V and L-AmB is a useful salvage therapy for IA refractory to AmB. These results will have to be confirmed in larger studies.
2002

abstract No: 

M-860

Full conference title: 

42nd Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 42nd