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Indifferent Effect of Nonsteroidal Anti-Inflammatory Drugs (Nsaids) Combined With Fluconazole Against Multidrug-Resistant Candida Auris Publisher



Ahangarkani F1, 2 ; Khodavaisy S3, 4 ; Mahmoudi S5, 6 ; Shokohi T2, 7 ; Rezai MS8 ; Fakhim H6 ; Dannaoui E9 ; Faraji S1 ; Chowdhary A10 ; Meis JF11, 12 ; Badali H7, 13
Authors
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Authors Affiliations
  1. 1. Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
  2. 2. Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran
  3. 3. Zoonoses Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
  4. 4. Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Students Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Medical Parasitology and Mycology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  7. 7. Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
  8. 8. Pediatric Infectious Diseases Research Center, Mazandaran University of Medical Sciences, Sari, Iran
  9. 9. Universite Paris-Descartes, Faculte de Medecine, APHP, Hopital Europeen Georges Pompidou, Unite de Parasitologie-Mycologie, Service de Microbiologie, Paris, France
  10. 10. Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India
  11. 11. Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital (CWZ), Nijmegen, Netherlands
  12. 12. Center of Expertise in Mycology Radboudumc/CWZ, Nijmegen, Netherlands
  13. 13. Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran

Source: Current Medical Mycology Published:2019


Abstract

Background and Purpose: Emergence and development of antifungal drug resistance in Candida species constitute a serious concern. Candida auris as an emerging multidrug-resistant fungus is the most important public health threat with high levels of mortality and morbidity. Almost all C. auris isolates are resistant to fluconazole, and there have been reports of elevated minimum inhibitory concentrations (MICs) to amphotericin B and echinocandins. To overcome the growing challenge of antifungal resistance, a valuable alternative option would be the use of drug combination. Materials and Methods: The present study evaluated the in vitro combination of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, diclofenac and aspirin with fluconazole against fluconazole-resistant C. auris in comparison to other fluconazole-resistant Candida species, including C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei originating from patients with candidiasis. Results: The MIC ranges of fluconazole-ibuprofen and fluconazole-diclofenac decreased from 32-256 to 32-128 and 16-256 µg/ml, respectively and remained the same for fluconazole-aspirin against C. auris. However, the combination of fluconazole with ibuprofen resulted in a synergistic effect for 5 strains, including C. albicans (n=2), C. tropicalis (n=1), C. glabrata (n=1), and C. krusei (n=1), by decreasing the MIC of fluconazole by 2-3 log2 dilutions. Conclusion: Although the interaction of NSAIDs with fluconazole was not synergistic against fluconazole-resistant C. auris isolates, no antagonism was observed for any combinations. Therefore, combination with newer azole agents needs to be conducted. Copyright © 2019, Published by Mazandaran University of Medical Sciences on behalf of Iranian Society of Medical Mycology and Invasive Fungi Research Center.
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