In vitro interactions of crocin with fluconazole against Candida isolates


1 Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Invasive Fungi Research Centre, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

3 Department of Medical Sciences, Islamic Azad University, Sari Branch, Sari, Iran

4 Neurocognitive Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5 Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran

6 Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran


Background and Purpose: The incidence of invasive fungal infections has been increased in recent years. The growing use of azole drugs for prophylactic and therapeutic purposes has resulted in the gradual emergence of azole-resistant species. Accordingly, the introduction of a new strategy to improve the management of Candida infections is an urgent need. Regarding this, the present study was performed to evaluate the antifungal activities of crocin (Cro) alone and in combination with fluconazole.
Materials and Methods: This study was conducted on 50 clinical isolates of four different Candida species. The identity of the isolates was confirmed using the internal transcribed spacer identification system. The interactions of Cro with fluconazole were investigated using a microdilution checkerboard method based on the Clinical and Laboratory Standards Institute reference technique with 96-well microtiter plates. Furthermore, the assessment of the interaction of drug combinations was accomplished using the fractional inhibitory concentration index (FICI) based on the Loewe additivity theory.
Results: According to the results, Cro alone showed a relatively high MIC50 value (1 g/ml) against Candida species. Our results demonstrated indifferent interactions between Cro and fluconazole with a FICI range of 0.5-4 against Candida strains.
Conclusion: The high MIC value for Cro against Candida species indicated its failure to show appropriate antifungal activity against this species. The MIC of this agent was not significantly reduced even by the addition of fluconazole. Therefore, other mechanisms which are not related to the mechanism of azole drugs are involved at high concentration of Cro.


Volume 4, Issue 4
December 2018
Pages 25-30
  • Receive Date: 09 July 2019
  • Revise Date: 09 October 2020
  • Accept Date: 09 July 2019
  • First Publish Date: 09 July 2019