Efficacy and Pharmacodynamic of Voriconazole combined with Anidulafungin in azole resistant invasive aspergillosis

Ref ID: 18654

Author:

S. Seyedmousavi, DVM (Dr Veterinary Medicine) – Scentific researcher1,2, R. J. M. Bruggemann – Dr 3,2, W. J. G. Melchers – Dr 1,2, J. W. Mouton – Dr 1,2, P. E. Verweij – Professor 1,2;

Author address:

1Dept.s of Med. Microbiol., Radboud university Nijmegen medical center, Nijmegen, Netherlands, 2Nijmegen Inst. for Infection, Inflammation and Immunity, Nijmegen, Netherlands, 3Dept.s of Clinical Pharmacy,Radboud university Nijmegen medical center, N

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: Invasive aspergillosis (IA) is an increasingly common infection of both immunocompromised and non-immunocompromised patients. Despite advances in treatment of IA, azole resistant infections are associated with treatment failure and excess mortality. Combination therapy is a promising approach to improve therapeutic outcome in azole resistant IA. Methods: We studied in vivo antifungal efficacy of voriconazole (VCZ) combined with anidulafungin (AFG) against clinical Aspergillus fumigatus isolates with MICs of 0.25 and 4 mg/liter for VCZ and 0.03 mg/liter for AFG (TR/L98H and a wild-type control isolate) which obtained from patients with IA. Treatment groups were consisted the combination of VCZ and AFG at 2.5, 5, 10 and 20 mg / kg of body weight/day. Intra peritoneal therapy was begun 24 h after challenge for 7 consecutive days. Survival used as the end point, and further assessment of fungal burden in kidney was performed by quantitative PCR. Results: The efficacy of combination therapy was comparable to VCZ or AFG monotherapy. VCZ showed excellent therapeutic efficacy (100% survival) in 20 mg/kg for isolate with 0.25 mg/liter of VCZ. Significantly, addition of 5 mg/kg VCZ to 20 mg/kg of AFG and 10 mg/kg VCZ to 10 or 20mg/kg of AFG resulted in prolongation of survival to 100%.The efficacy of voriconazole for isolate with high MIC( 4mg/liter) was increased to100% in the combination of 20mg/kg VCZ with 10 or 20mg/kg AFG and also reduced fungal burden. Conclusions: These results indicate that survival was dependent both on the dose and on the MIC. The combination of VCZ plus AFG is therapeutically effective in the treatment of non-neutropenic mouse model of IA. Significantly, this approach is superior to the use of VCZ or AFG monotherapy when infection is caused by azole resistant Aspergillus fumigatus isolates.

Abstract Number: A2-584

Conference Year: 2012

Link to conference website: NULL

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