Indifferent effect of nonsteroidal anti-inflammatory drugs (NSAIDs) combined with fluconazole against multidrug-resistant Candida auris

Document Type : Original Articles

Authors

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

2 Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran

3 Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

4 Zoonoses Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

5 Students Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran

6 Department of Medical Parasitology and Mycology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

7 Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

8 Pediatric Infectious Diseases Research Center, Mazandaran University of Medical Sciences, Sari, Iran

9 Université Paris-Descartes, Faculté de Médecine, APHP, Hôpital Européen Georges Pompidou, Unité de Parasitologie-Mycologie, Service de Microbiologie, Paris, France

10 Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India

11 Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital (CWZ), Nijmegen, The Netherlands

12 Center of Expertise in Mycology Radboudumc/CWZ, Nijmegen, The Netherlands

13 Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran

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.

Keywords

Main Subjects

References

1. Lamoth F, Lockhart SR, Berkow EL, Calandra T. Changes in the epidemiological landscape of invasive candidiasis. J Antimicrob Chemother. 2018; 73:i4-13.
2. Cortegiani A, Misseri G, Chowdhary A. What’s new on emerging resistant Candida species. Intensive Care Med. 2019; 45(4):512-5.
3. Meis JF, Chowdhary A. Candida auris: a global fungal public health threat. Lancet Infect Dis. 2018; 18(12):1298-9.
4. Satoh K, Makimura K, Hasumi Y, Nishiyama Y, Uchida K, Yamaguchi H. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol. 2009; 53(1):41-4.
5. Calvo B, Melo AS, Perozo-Mena A, Hernandez M, Francisco EC, Hagen F, et al. First report of Candida auris in America: Clinical and microbiological aspects of 18 episodes of candidemia. J Infect. 2016; 73(4):369-74.
6. Ruiz-Gaitán A, Moret AM, Tasias-Pitarch M, Aleixandre-López AI, Martínez-Morel H, Calabuig E, et al. An outbreak due to Candida auris with prolonged colonisation and candidaemia in a tertiary care European hospital. Mycoses. 2018; 61(7):498-505.
7. Chow NA, Gade L, Tsay SV, Forsberg K, Greenko JA, Southwick KL, et al. Multiple introductions and subsequent transmission of multidrug-resistant Candida auris in the USA: a molecular epidemiological survey. Lancet Infect Dis. 2018; 18(12):1377-84.
8. Araúz AB, Caceres DH, Santiago E, Armstrong P, Arosemena S, Ramos C, et al. Isolation of Candida auris from 9 patients in Central America: importance of accurate diagnosis and susceptibility testing. Mycoses. 2018; 61:44-7.
9. Schelenz S, Hagen F, Rhodes JL, Abdolrasouli A, Chowdhary A, Hall A, et al. First hospital outbreak of the globally emerging Candida auris in a European hospital. Antimicrob Resist Infect Control. 2016; 5:35.
10. Eyre DW, Sheppard AE, Madder H, Moir I, Moroney R, Quan TP, et al. A Candida auris outbreak and its control in an intensive care setting. N Engl J Med. 2018; 379(14):1322-31.
11. Saris K, Meis JF, Voss A. Candida auris. Curr Opin Infect Dis. 2018; 31(4):334-40.
12. Abastabar M, Haghani I, Ahangarkani F, Rezai MS, Taghizadeh Armaki M, Roodgari S, et al. Candida auris otomycosis in Iran and review of recent literature. Mycoses. 2019; 62(2):101‐5.
13. Forsberg K, Woodworth K, Walters M, Berkow EL, Jackson B, Chiller T, et al. Candida auris: the recent emergence of a multidrug-resistant fungal pathogen. Med Mycol. 2019; 57(1):1-12.
14. Biswal M, Rudramurthy SM, Jain N, Shamanth AS, Sharma D, Jain K, et al. Controlling a possible outbreak of Candida auris infection: lessons learnt from multiple interventions. J Hosp Infect 2017; 97(4):363-70.
15. Lee WG, Shin JH, Uh Y, Kang MG, Kim SH, Park KH, et al. First three reported cases of nosocomial fungemia caused by Candida auris. J Clin Microbiol. 2011; 49(9):3139-42.
16. Chowdhary A, Prakash A, Sharma C, Kordalewska M, Kumar A, Sarma S, et al. A multicenter study of antifungal susceptibility patterns among 350 Candida auris isolates (2009-
17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. J Antimicrob Chemother. 2018; 73(4):891-9.
17. Escandón P, Chow NA, Caceres DH, Gade L, Berkow EL, Armstrong P, et al. Molecular epidemiology of Candida auris in Colombia reveals a highly related, countrywide colonization with regional patterns in Amphotericin B resistance. Clin Infect Dis. 2019; 68(1):15-21.
18. Mathur P, Hasan F, Singh PK, Malhotra R, Walia K, Chowdhary A. Five-year profile of candidaemia at an Indian trauma centre: high rates of Candida auris blood stream infections. Mycoses. 2018; 61(9):674-80.
19. Butts A, Krysan DJ. Antifungal drug discovery: something old and something new. PLoS Pathog. 2012; 8(9):e1002870.
20. Lan YB, Huang YZ, Qu F, Li JQ, Ma LJ, Yan J, et al. Time course of global gene expression alterations in Candida albicans during infection of HeLa cells. Bosn J Basic Med Sci. 2017; 17(2):120-31.
21. Pina-Vaz C, Sansonetty F, Rodrigues AG, Martinez-De-Oliveira J, Fonseca AF, Mårdh PA. Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species. J Med Microbiol. 2000; 49(9):831-40.
22. de Quadros AU, Bini D, Pereira PA, Moroni EG, Monteiro MC. Antifungal activity of some cyclooxygenase inhibitors on Candida albicans: PGE2-dependent mechanism. Folia Microbiol. 2011; 56(4):349-52.
23. Scott EM, Tariq VN, McCrory RM. Demonstration of synergy with fluconazole and either ibuprofen, sodium salicylate, or propylparaben against Candida albicans in vitro. Antimicrob Agents Chemother. 1995; 39(12):2610-4.
24. Krol J, Nawrot U, Bartoszewicz M. Anti-candidal activity of selected analgesic drugs used alone and in combination with fluconazole, itraconazole, voriconazole, posaconazole and isavuconazole. J Mycol Med. 2018; 28(2):327-31.
25. Yucesoy M, Oktem IM, Gulay Z. In-vitro synergistic effect of fluconazole with nonsteroidal anti-inflammatory agents against Candida albicans strains. J Chemother. 2000; 12(5):385-9.
26. Aslani N, Janbabaei G, Abastabar M, Meis JF, Babaeian M, Khodavaisy S, et al. Identification of uncommon oral yeasts from cancer patients by MALDI-TOF mass spectrometry. BMC Infect Dis. 2018; 18(1):24.
27. CLSI. Reference method for broth dilution antifungal susceptibility testing of yeast; approved standards, (M27-A3). 3rd ed. Wayne, PA: CLSI; 2008. P. 14.
28. Pfaller MA. Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med. 2012; 125(1 Suppl):S3-13.
29. Liu JY, Shi C, Wang Y, Li WJ, Zhao Y, Xiang MJ. Mechanisms of azole resistance in Candida albicans clinical isolates from Shanghai, China. Res Microbiol. 2015; 166(3):153-61.
30. Odds FC. Synergy, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother. 2003; 52(1):1.
31. Hyde KD, Al-Hatmi AM, Andersen B, Boekhout T, Buzina W, Dawson TL, et al. The world’s ten most feared fungi. Fungal Divers. 2018; 93(1):161-94.
32. Chowdhary A, Voss A, Meis JF. Multidrug-resistant Candida auris: 'new kid on the block' in hospital-associated infections? J Hosp Infect. 2016; 94(3):209-12.
33. Chow NA, de Groot T, Badali H, Abastabar M, Chiller TM, Meis JF. Potential fifth clade of Candida auris, Iran, 2018. Emerg Infect Dis. 2019; 25(9):1780-1.
34. Khan Z, Ahmad S, Al-Sweih N, Joseph L, Alfouzan W, Asadzadeh M, et al. Increasing prevalence, molecular characterization and antifungal drug susceptibility of serial Candida auris isolates in Kuwait. PLoS One. 2018; 13(4): e0195743.
35. Fakhim H, Chowdhary A, Prakash A, Vaezi A, Dannaoui E, Meis JF,et al. In vitro interactions of echinocandins with triazoles against multidrug-resistant Candida auris. Antimicrob Agents Chemother. 2017; 61(11):e01056-17.
36. Eldesouky HE, Mayhoub A, Hazbun TR, Seleem MN. Reversal of azole resistance in Candida albicans by sulfa antibacterial drugs. Antimicrob Agents Chemother. 2018; 62(3):e00701-17.
37. Eldesouky HE, Li X, Abutaleb NS, Mohammad H, Seleem MN. Synergistic interactions of sulfamethoxazole and azole antifungal drugs against emerging multidrug-resistant Candida auris. Int J Antimicrob Agents. 2018; 52(6):754-761. 
38. Mahmoudi S, Rezaie S, Ghazvini RD, Hashemi SJ, Badali H, Foroumadi A, et al. In Vitro interaction of geldanamycin with triazoles and echinocandins against common and emerging Candida species. Mycopathologia. 2019; 184(5):607-613.
Current Medical Mycology
Volume 5, Issue 3
September 2019
Pages 26-30

Files

Share

How to cite

Statistics