In vitro combination of voriconazole with micafungin against azole-resistant clinical isolates of Aspergillus fumigatus from different geographical regions

H Fakhim1,2, A Vaezi3,4, E Dannaoui5, C Sharma6, B Mousavi7, A Chowdhary6, JF Meis8,9, H Badali3,10

Author address: 

1Department of Medical Parasitology and Mycology, Urmia University of Medical Sciences, Urmia, Iran 2Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran 3Department of Medical Mycology and Parasitology, Mazandaran University of Medical Sciences, Sari, Iran 4Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran 5Unité de Parasitologie-Mycologie, Service de Microbiologie, Hôpital Européen Georges Pompidou, Paris, France 6Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India 7Dynamyc Research Group (EA 7380), Paris Est Créteil University, Paris, France 8Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital (CWZ), Nijmegen, Netherlands 9Center of Expertise in Mycology Radboudumc/CWZ, Canisius-Wilhelmina Hospital (CWZ), Nijmegen, Netherlands 10Pharmaceutical Sciences Research Center , Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran

Abstract: 

Introduction: Azole-resistant Aspergillus fumigatus isolates have emerged as a major source of life threatening aspergillosis in hospitalized patients with significant morbidity and mortality. Voriconazole is the recommended drug of choice to treat aspergillosis. However, the combination of voriconazole with micafungin could improve therapeutic outcomes in azole-resistant invasive aspergillosis.

Methods: The in vitro interaction of voriconazole with micafungin was evaluated against clinical Aspergillus fumigatus isolates, originating from different geographical regions and harboring various azole-resistance mechanisms.

Results: The range of voriconazole minimum inhibitory concentrations (MICs) and micafungin minimum effective concentrations (MECs) when tested alone were 0.125 - >16 µg/ml and 0.002 - 0.031 µg/ml, respectively. Interaction between voriconazole and micafungin was synergistic for only one resistant isolates carrying the TR34/ L98H mutation. No antagonistic effects were observed for 96.8 % of azole-resistant isolates.

Conclusion: Further in vivo studies are needed to determine whether and how combination therapy can assist to reduce the treatment failure associated with azole-resistance.

2018

Full conference title: 

The 8th Advances Against Aspergillus, Lisbon Conference Center, Lisbon, Portugal
    • AAA 8th (2018)