JAC Advance Access published online on November 3, 2009
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkp397
Original research |
Treatment outcome of invasive mould disease after sequential exposure to azoles and liposomal amphotericin B
1 Klinik I für Innere Medizin and Zentrum für Klinische Studien (BMBF 01KN0706), Universität zu Köln, Köln, Germany 2 Department of Haematology, Universitaire Ziekenhuizen Leuven, Leuven, Belgium 3 Gilead Sciences, Foster City, CA, USA 4 Universitätsklinik, 3rd Medical Department, Johannes Gutenberg-University, Mainz, Germany 5 Hematology and Oncology Department, Hopital de Hautepierre, Strasbourg, France
Received 24 July 2009; returned 6 August 2009; revised 6 October 2009; accepted 11 October 2009
* Corresponding author. Klinik I für Innere Medizin der Universität zu Köln, and Zentrum für Klinische Studien (BMBF 01KN0706), Kerpener Strasse 62, 50937 Cologne, Germany. Tel: +49-221-478-6494; Fax: +49-221-478-3611; E-mail: oliver.cornely{at}ctuc.de
Objectives: To analyse the potential antagonism between azoles, which inhibit ergosterol synthesis, and polyenes, which bind directly to ergosterol in cell membranes, in patients receiving sequential azole–polyene treatment.
Methods: In an earlier randomized, double blind study of liposomal amphotericin as initial therapy for invasive filamentous fungal infection (IFFI), a 3 mg/kg/day dose had a favourable overall response rate of 50% and 12 week survival rate of 72%. No improved outcome was seen with 10 mg/kg/day for the first 14 days. The study population was further analysed for the effect of prior azole exposure on treatment responses to liposomal amphotericin B. The protocol allowed prior treatment with azoles for prophylaxis or empirical therapy, and for up to 4 days for the confirmed IFFI before starting liposomal amphotericin B. Outcomes were compared for subsets of patients based on receipt of any azole and receipt of voriconazole during the 30 day screening period prior to study treatment.
Results: Of 201 patients with data review board-confirmed IFFI, 116 (57.7%) received prior azoles and 36 (17.9%) received prior voriconazole. Favourable responses were achieved in 57 (49.1%) patients with prior azole exposure, in 39 (45.9%) without prior azole and in 13 (36.1%) with prior voriconazole. Numbers of patients alive at 12 weeks were 74 (63.8%) with any prior azole, 56 (65.9%) without prior azole and 26 (72.2%) after prior voriconazole. No differences were statistically significant.
Conclusions: Prior treatment with any azole or specifically with voriconazole did not seem to impact on overall response or survival in patients treated with liposomal amphotericin B for confirmed IFFI.
Key Words: aspergillosis , polyenes , antagonism