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.
Full conference title:
- AAA 8th (2018)