Evaluating the combined impact of amphotericin B and posaconazole on the germination of a rare Rhizopus homothallicus isolate responsible for COVID-19 associated mucormycosis.

BACKGROUND

During the COVID-19 pandemic, Rhizopus arrhizus and Rhizopus homothallicus were identified as causative agents of rhino-cerebral mucormycosis in COVID-19 patients. Clinical management typically includes surgical debridement and antifungal treatment, with amphotericin B (AMB) and posaconazole (PCZ) as primary options. However, long-term use of AMB can lead to toxicity, necessitating PCZ as a follow-up treatment.

AIMS: This study aimed to examine the combined effect of AMB and PCZ on R. homothallicus.

METHODS

The combined effect of AmB and PCZ on R. homothallicus was studied by examining their minimum inhibitory concentration (MIC) values, fractional inhibitory concentration index (FICI), spore germination properties, viability, and intracellular reactive oxygen species accumulation; Raman spectroscopy was also performed.

RESULTS

The MIC values for AmB and PCZ were 4 and 8μg/mL, respectively, with a combined MIC of 2μg/mL and an FICI index of <0.28. The germination rates at MIC values after 48h of exposure were 28% for AmB, 36% for PCZ, and only 3% for the combination. Viability assays revealed dead sporangiospores following combination treatment. AmB and its combination generated more ROS (68.18% and 64.45%, respectively) than did PCZ alone (42.6%).

CONCLUSIONS

Combination therapy reduced the AMB dose without loss of efficacy, suggesting a synergistic effect against R. homothallicus. These results may support this alternative strategy to mitigate the side effects of AMB.