In Vitro Activity of Amphotericin B in Combination with Statins against Clinical and Environmental Rhizopus oryzae Strains

BACKGROUND: Mucormycosis is an acute and invasive fungal infection with a high mortality rate. Mucorales are less sensitive than other types of fungi to most antifungal agents. Amphotericin B (AMB) is one treatment option for this infection, but in recent studies, the antifungal activity of statins against Mucorales was shown. Therefore, therapy that combines AMB with these agents may have better effects in management of patients with mucormycosis. We evaluated the in vitro activity of AMB alone and in combination with statins, against Mucorales. METHODS: Susceptibility profiles of AMB alone and in combination with two statins, atorvastatin (ATO) and lovastatin (LOV) determined against clinical (n: 15) and environmental (n: 5) Rhizopus oryzae isolates, obtained between Jan 2009 and Oct 2016 from patients with uncontrolled diabetes mellitus and cancer referred to the Department of Parasitology and Medical Mycology of Tehran University of Medical Sciences, Tehran, Iran. It was performed by microdilution method, based on the Clinical and Laboratory Standard Institute (CLSI) M38-A2 guideline. RESULTS: All clinical and environmental isolates were susceptible to AMB (MIC≤1 μg/mL). The results of the interactions between AMB and the two statins were positive. The AMB-ATO (GM: 0.13 μg/Ml) combination produced greater activity than the AMB-LOV (GM: 0.26 μg/mL) combination. AMB, in combination with ATO and LOV, reacts positively against clinical and environmental R. oryzae isolates. CONCLUSION: This combination strategy may lead to more effective treatment of mucormycosis and fewer side effects using low dose of AMB.