Voriconazole (VCZ) for Bone Aspergillosis (BA): a Worldwide Experience of 19 Cases.

O. LORTHOLARY, H. MOUAS-DUPUY, B. DUPONT, I. LUTSAR4, O. FAIN

Author address: 

Avicenne Univ. Hosp., Bobigny, France, Inst. Pasteur, Paris, France, Necker Univ. Hosp., Paris, France, Pfizer Ltd., Sandwich, United Kingdom, Jean Verdier Univ. Hosp., Bondy, France.

Abstract: 

Background: Bone involvement is a rare but serious complication of invasive aspergillosis (IA). VCZ is effective for pulmonary IA, has excellent penetration into various tissues, and therefore has the clinical potential to be effective for BA. Methods: All patients (pt) with definite or probable IA and bone involvement were selected from a global database of pt treated with VCZ. Certainty of diagnosis was assessed using EORTC/MSG criteria. Global response (clinical, radiological, and mycological results) was evaluated at end of treatment (EOT). Results: 19 pt were included (16 male, 3 female; mean age 35.4, range 4-78y); 9 from clinical trials and 10 from the compassionate use program. Underlying conditions affecting ³ 2 pt included chronic granulomatous disease (5 pt), hematologic malignancies (2), and solid organ transplantation (2). 4 pt were immunocompetent. Bone was the only infection site in 8 pt. The commonest presentation was spondylodiscitis (9 pt); other bones involved were ribs (4 pt), wrist, mastoid, maxilla, mandibula, and sternum. Causative organisms included: A fumigatus (14), A terreus (2), A nidulans (1), A versicolor (1), and aspergillus spp (1). 17 pt had received prior antifungal therapy, including amphotericin B (17), itraconazole (10), and flucytosine (4). 12 pt started with IV VCZ (7 were later switched to oral VCZ); 7 pt received oral VCZ only. Median duration of VCZ therapy was 80.5 days (range 4-296d). Response at EOT was complete in 3 pt, partial in 7, and failure in 9. 3 pt died on therapy: 2 due to underlying disease and 1 due to progression of fungal infection; 2 others died >60d after EOT. 12 pt experienced ³ 1 treatment-related AEs but only 2 discontinued VCZ (due to increased LFTs or rash). Conclusions: With a global response rate of 52% (10/19) and acceptable safety profile, VCZ is an attractive therapeutic option for pt with BA.
2003

abstract No: 

M-979

Full conference title: 

43rd Interscience Conference on Antimicrobial Agents
    • ICAAC 43rd