OBJECTIVES: Azole resistance is an emerging problem in the treatment of Aspergillus fumigatus infections. Combination therapy may be an alternative approach to improve therapeutic outcome in azole-resistant invasive aspergillosis (IA). The in vivo efficacy of voriconazole and anidulafungin was investigated in a non-neutropenic murine model of IA using voriconazole-susceptible and voriconazole-resistant A. fumigatus clinical isolates. METHODS: Treatment groups consisted of voriconazole monotherapy, anidulafungin monotherapy and voriconazole + anidulafungin at 2.5, 5, 10 and 20 mg/kg body weight/day for 7 consecutive days. In vitro and in vivo drug interactions were analysed by non-parametric Bliss independence and non-linear regression analysis. RESULTS: Synergistic interaction between voriconazole and anidulafungin against the voriconazole-susceptible isolate (AZN 8196) was observed in vitro and in vivo. However, among animals infected with the voriconazole-resistant isolate (V 52-35), 100% survival was observed only in groups receiving the highest doses (20 mg/kg voriconazole + 20 mg/kg anidulafungin). For this isolate, additivity, but not synergy, was observed in vivo. CONCLUSIONS: Combination of voriconazole and anidulafungin was synergistic in voriconazole-susceptible IA, but additive in voriconazole-resistant IA. There is a clear benefit of combining voriconazole and anidulafungin, but the reduced effect of combination therapy in azole-resistant IA raises some concern.
OBJECTIVES:Azole resistance is an emerging problem in the treatment of Aspergillus fumigatus infections. Combination therapy may be an alternative approach to improve therapeutic outcome in azole-resistant invasive aspergillosis (IA). The in vivo efficacy of voriconazole and anidulafungin was investigated in a non-neutropenicmurine model of IA using voriconazole-susceptible and voriconazole-resistant A. fumigatus clinical isolates. METHODS: Treatment groups consisted of voriconazole monotherapy, anidulafungin monotherapy and voriconazole + anidulafungin at 2.5, 5, 10 and 20 mg/kg body weight/day for 7 consecutive days. In vitro and in vivo drug interactions were analysed by non-parametric Bliss independence and non-linear regression analysis. RESULTS: Synergistic interaction between voriconazole and anidulafungin against the voriconazole-susceptible isolate (AZN 8196) was observed in vitro and in vivo. However, among animals infected with the voriconazole-resistant isolate (V 52-35), 100% survival was observed only in groups receiving the highest doses (20 mg/kg voriconazole + 20 mg/kg anidulafungin). For this isolate, additivity, but not synergy, was observed in vivo. CONCLUSIONS: Combination of voriconazole and anidulafungin was synergistic in voriconazole-susceptible IA, but additive in voriconazole-resistant IA. There is a clear benefit of combining voriconazole and anidulafungin, but the reduced effect of combination therapy in azole-resistant IA raises some concern.
Authors: Seyedmojtaba Seyedmousavi; Roger J M Brüggemann; Jacques F Meis; Willem J G Melchers; Paul E Verweij; Johan W Mouton Journal: Antimicrob Agents Chemother Date: 2015-03-09 Impact factor: 5.191
Authors: Shivaprakash M Rudramurthy; Seyedmojtaba Seyedmousavi; Manpreet Dhaliwal; Arunaloke Chakrabarti; Jacques F Meis; Johan W Mouton Journal: Antimicrob Agents Chemother Date: 2016-12-27 Impact factor: 5.191
Authors: A Arastehfar; A Carvalho; J Houbraken; L Lombardi; R Garcia-Rubio; J D Jenks; O Rivero-Menendez; R Aljohani; I D Jacobsen; J Berman; N Osherov; M T Hedayati; M Ilkit; D James-Armstrong; T Gabaldón; J Meletiadis; M Kostrzewa; W Pan; C Lass-Flörl; D S Perlin; M Hoenigl Journal: Stud Mycol Date: 2021-05-10 Impact factor: 16.097
Authors: Seyedmojtaba Seyedmousavi; Willem J G Melchers; Johan W Mouton; Paul E Verweij Journal: Antimicrob Agents Chemother Date: 2013-02-04 Impact factor: 5.191