The high efficacy of luliconazole against environmental and otomycosis Aspergillus flavus strains
Abstract
Background and Objectives: Luliconazole is currently confirmed for the topical therapy of dermatophytosis. Moreover, it is found that luliconazole has in vitro activity against some molds and yeast species. The aim of the present study was to evaluate the efficacy of luliconazole in comparison to routine used antifungals on clinical and environmental isolates of Aspergillus flavus.
Materials and Methods: Thirty eight isolates of A. flavus (18 environmental and 20 clinical isolates) were detected based on morphological and microscopic features and also PCR-sequencing of β-tubulin ribosomal DNA gene. All the isolates were tested against luliconazole, voriconazole, amphotericin B and caspofungin. Minimum inhibitory concentration (MIC), MIC50, MIC90 and MIC Geometric (GM) were calculated using CLSI M38-A2 protocol for both environmental and clinical isolates.
Results: Luliconazole with extremely low MIC range, 0.00049-0.00781 μg/mL and MICGM 0.00288 μg/mL showed very strong activity against both clinical and environmental A. flavus isolates. Moreover, voriconazole inhibited 100% of isolates at defined epidemiological cutoff values (ECV ≤ 2 µg/ml). 50% and 27.8% of clinical and environmental isolates of A. flavus, were resistant to caspofungin, respectively. Whereas, all the isolates were found to be resistant to amphotericin B.
Conclusion: The analysis of our data clearly indicated that luliconazole (with MICGM 0.00244 µg/ml for clinical and 0.00336 μg/ml for environmental isolates) had the highest in vitro activity against A. flavus strains.
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2. Abastabar M, Rahimi N, Meis JF, Aslani N, Khodavaisy S, Nabili M, et al. Potent activities of novel imidazoles lanoconazole and luliconazole against a collection of azole-resistant and -susceptible Aspergillus fumigatus strains. Antimicrob Agents Chemother 2016;60:6916-6919.
3. Koga H, Nanjoh Y, Kaneda H, Yamaguchi H, Tsuboi R. Short-term therapy with luliconazole, a novel topical antifungal imidazole, in guinea pig models of tinea corporis and tinea pedis. Antimicrob Agents Chemother 2012;56:3138-3143.
4. Gupta AK, Daigle D. A critical appraisal of once-daily topical luliconazole for the treatment of superficial fungal infections. Infect Drug Resist 2016;9:1-6.
5. Zargaran M, Taghipour S, Kiasat N, Aboualigalehdari E, Rezaei-Matehkolaei A, Zarei Mahmoudabadi A, et al. Luliconazole, an alternative antifungal agent against Aspergillus terreus. J Mycol Med 2017;27:351-356.
6. Taghipour S, Kiasat N, Shafiei S, Halvaeezadeh M, Rezaei-Matehkolaei A, Zarei Mahmoudabadi A. Luliconazole, a new antifungal against Candida species isolated from different sources. J Mycol Med 2018;28:374-378.
7. Omran SM, Taghizadeh-Armaki M, Zarrinfar H, Hedayati MT, Abastabar M, Moqarabzadeh V, et al. In-vitro antifungal susceptibility testing of lanoconazole and luliconazole against Aspergillus flavus as an important agent of invasive aspergillosis. J Infect Chemother 2019;25:157-160.
8. Reichert-Lima F, Lyra L, Pontes L, Moretti ML, Pham CD, Lockhart SR, et al. Surveillance for azoles resistance in Aspergillus spp. highlights a high number of amphotericin B-resistant isolates. Mycoses 2018;61:360-365.
9. Vaezi A, Fakhim H, Arastehfar A, Shokohi T, Hedayati MT, Khodavaisy S, et al. In vitro antifungal activity of amphotericin B and 11 comparators against Aspergillus terreus species complex. Mycoses 2018;61:134-142.
10. Borman AM, Fraser M, Palmer MD, Szekely A, Houldsworth M, Patterson Z, et al. MIC distributions and evaluation of fungicidal activity for amphotericin b, itraconazole, voriconazole, posaconazole and caspofungin and 20 species of pathogenic filamentous fungi determined using the CLSI broth microdilution method. J Fungi (Basel) 2017;3:E27.
11. Bedin Denardi L, Hoch Dalla-Lana B, Pantella Kunz de Jesus F, Bittencourt Severo C, Morais Santurio J, Zanette RA, et al. In vitro antifungal susceptibility of clinical and environmental isolates of Aspergillus fumigatus and Aspergillus flavus in Brazil. Braz J Infect Dis 2018;22:30-36.
12. Diekema DJ, Messer SA, Hollis RJ, Jones RN, Pfaller MA. Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi. J Clin Microbiol 2003;41:3623-3626.
13. Dannaoui E, Gabriel F, Gaboyard M, Lagardere G, Audebert L, Quesne G, et al. Molecular diagnosis of invasive aspergillosis and detection of azole resistance by a newly commercialized PCR kit. J Clin Microbiol 2017;55:3210-3218.
14. Ukai Y, Kuroiwa M, Kurihara N, Naruse H, Homma T, Maki H, et al. Contributions of yap1 mutation and subsequent atrf upregulation to voriconazole resistance in Aspergillus flavus. Antimicrob Agents Chemother 2018;62(11): e01216-18.
15. Siopi M, Pournaras S, Meletiadis J. Comparative evaluation of sensititre yeastone and clsi m38-a2 reference method for antifungal susceptibility testing of Aspergillus spp. against Echinocandins. J Clin Microbiol 2017;55:1714-1719.
16. Sharma S, Yenigalla BM, Naidu SK, Pidakala P. Primary cutaneous aspergillosis due to Aspergillus tamarii in an immunocompetent host. BMJ Case Rep 2013;2013:010128.
17. Rudramurthy SM, Paul RA, Chakrabarti A, Mouton JW, Meis JF. Invasive aspergillosis by Aspergillus flavus: epidemiology, diagnosis, antifungal resistance, and management. J Fungi (Basel) 2019;5: E55.
18. Kiakojori K, Bagherpour Jamnani N, Khafri S, Mahdavi Omran S. Assessment of response to treatment in patients with otomycosis. Iran J Otorhinolaryngol 2018;30:41-47.
19. Taghizadeh-Armaki M, Hedayati MT, Ansari S, Omran SM, Saber S, Rafati H, et al. Genetic diversity and in vitro antifungal susceptibility of 200 clinical and environmental Aspergillus flavus isolates. Antimicrob Agents Chemother 2017;61(5): e00004-17.
20. Rudramurthy SM, Seyedmousavi S, Dhaliwal M, Chakrabarti A, Meis JF, Mouton JW. Pharmacodynamics of voriconazole against wild-type and azole-resistant Aspergillus flavus isolates in a nonneutropenic murine model of disseminated aspergillosis. Antimicrob Agents Chemother 2016;61(1): e01491-16.
21. Mosquera J, Warn P, Morrissey J, Moore C, Gil-Lamaignere C, Denning D. Susceptibility testing of Aspergillus flavus: inoculum dependence with itraconazole and lack of correlation between susceptibility to amphotericin B in vitro and outcome in vivo. Antimicrob Agents Chemother 2001;45:1456-1462.
22. Odds F, Van Gerven F, Espinel-Ingroff A, Bartlett M, Ghannoum M, Lancaster M, et al. Evaluation of possible correlations between antifungal susceptibilities of filamentous fungi in vitro and antifungal treatment outcomes in animal infection models. Antimicrob Agents Chemother 1998;42:282-288.
23. Rodrigues P, Soares C, Kozakiewicz Z, Paterson R, Lima N, Venâncio A. Identification and characterization of Aspergillus flavus and aflatoxins. In Microbiology Book Series – Communicating Current Research and Educational Topics ed A Méndez-Vilas pp. 527– 534 Badajoz: Formatex 2007.
24. Sharma C, Kumar R, Kumar N, Masih A, Gupta D, Chowdhary A. Investigation of multiple resistance mechanisms in voriconazole-resistant Aspergillus flavus clinical isolates from a chest hospital surveillance in Delhi, India. Antimicrob Agents Chemother 2018;62(3): e01928-17.
25. Prencipe S, Siciliano I, Contessa C, Botta R, Garibaldi A, Gullino ML, et al. Characterization of Aspergillus section Flavi isolated from fresh chestnuts and along the chestnut flour process. Food Microbiol 2018;69:159-169.
26. CLSI (2017). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; 3rd ed. CLSI document M38-3rd. Wayne, PA: Clinical and Laboratory Standards Institute.
27. Watanabe S, Kishida H, Okubo A. Efficacy and safety of luliconazole 5% nail solution for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study. J Dermatol 2017;44:753-759.
28. Khodavaisy S, Badali H, Hashemi SJ, Aala F, Nazeri M, Nouripour-Sisakht S, et al. In vitro activities of five antifungal agents against 199 clinical and environmental isolates of Aspergillus flavus, an opportunistic fungal pathogen. J Mycol Med 2016;26:116-121.
29. Tissot F, Agrawal S, Pagano L, Petrikkos G, Groll AH, Skiada A, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 2017;102:433-444.
30. Xavier MO, Oliveira Fde M, Almeida V, Prolla G, Severo LC. Invasive Aspergillus flavus sinusitis: case report in a patient with biphenotypic acute leukemia. Rev Inst Med Trop Sao Paulo 2009;51:57-58.
31. Shokoohi GR, Badali H, Mirhendi H, Ansari S, Rezaei-Matehkolaei A, Ahmadi B, et al. In vitro activities of luliconazole, lanoconazole, and efinaconazole compared with those of five antifungal drugs against melanized fungi and relatives. Antimicrob Agents Chemother 2017;61(11): e00635-17.
32. Todokoro D, Suzuki T, Tamura T, Makimura K, Yamaguchi H, Inagaki K, et al. Efficacy of luliconazole against broad-range filamentous fungi including Fusarium solani species complex causing fungal keratitis. Cornea 2019;38:238-242.
33. Wiederhold NP, Fothergill AW, McCarthy DI, Tavakkol A. Luliconazole demonstrates potent in vitro activity against dermatophytes recovered from patients with onychomycosis. Antimicrob Agents Chemother 2014;58:3553-3555.
34. Hivary S, Fatahinia M, Halvaeezadeh M, Zarei Mahmoudabadi A. The potency of luliconazole against clinical and environmental Aspergillus Nigri complex. Iran J Microbiol 2019;11:510-519.
35. Varotto E, Putti MC, Sgarabotto D, Cecchin D, De Corti F, Beltrame V, et al. Aspergillus flavus disseminated infection in paediatric acute lymphoblastic leukaemia: A case report. Med Mycol: Open Access 2016;3:1-5.
2. Abastabar M, Rahimi N, Meis JF, Aslani N, Khodavaisy S, Nabili M, et al. Potent activities of novel imidazoles lanoconazole and luliconazole against a collection of azole-resistant and -susceptible Aspergillus fumigatus strains. Antimicrob Agents Chemother 2016;60:6916-6919.
3. Koga H, Nanjoh Y, Kaneda H, Yamaguchi H, Tsuboi R. Short-term therapy with luliconazole, a novel topical antifungal imidazole, in guinea pig models of tinea corporis and tinea pedis. Antimicrob Agents Chemother 2012;56:3138-3143.
4. Gupta AK, Daigle D. A critical appraisal of once-daily topical luliconazole for the treatment of superficial fungal infections. Infect Drug Resist 2016;9:1-6.
5. Zargaran M, Taghipour S, Kiasat N, Aboualigalehdari E, Rezaei-Matehkolaei A, Zarei Mahmoudabadi A, et al. Luliconazole, an alternative antifungal agent against Aspergillus terreus. J Mycol Med 2017;27:351-356.
6. Taghipour S, Kiasat N, Shafiei S, Halvaeezadeh M, Rezaei-Matehkolaei A, Zarei Mahmoudabadi A. Luliconazole, a new antifungal against Candida species isolated from different sources. J Mycol Med 2018;28:374-378.
7. Omran SM, Taghizadeh-Armaki M, Zarrinfar H, Hedayati MT, Abastabar M, Moqarabzadeh V, et al. In-vitro antifungal susceptibility testing of lanoconazole and luliconazole against Aspergillus flavus as an important agent of invasive aspergillosis. J Infect Chemother 2019;25:157-160.
8. Reichert-Lima F, Lyra L, Pontes L, Moretti ML, Pham CD, Lockhart SR, et al. Surveillance for azoles resistance in Aspergillus spp. highlights a high number of amphotericin B-resistant isolates. Mycoses 2018;61:360-365.
9. Vaezi A, Fakhim H, Arastehfar A, Shokohi T, Hedayati MT, Khodavaisy S, et al. In vitro antifungal activity of amphotericin B and 11 comparators against Aspergillus terreus species complex. Mycoses 2018;61:134-142.
10. Borman AM, Fraser M, Palmer MD, Szekely A, Houldsworth M, Patterson Z, et al. MIC distributions and evaluation of fungicidal activity for amphotericin b, itraconazole, voriconazole, posaconazole and caspofungin and 20 species of pathogenic filamentous fungi determined using the CLSI broth microdilution method. J Fungi (Basel) 2017;3:E27.
11. Bedin Denardi L, Hoch Dalla-Lana B, Pantella Kunz de Jesus F, Bittencourt Severo C, Morais Santurio J, Zanette RA, et al. In vitro antifungal susceptibility of clinical and environmental isolates of Aspergillus fumigatus and Aspergillus flavus in Brazil. Braz J Infect Dis 2018;22:30-36.
12. Diekema DJ, Messer SA, Hollis RJ, Jones RN, Pfaller MA. Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi. J Clin Microbiol 2003;41:3623-3626.
13. Dannaoui E, Gabriel F, Gaboyard M, Lagardere G, Audebert L, Quesne G, et al. Molecular diagnosis of invasive aspergillosis and detection of azole resistance by a newly commercialized PCR kit. J Clin Microbiol 2017;55:3210-3218.
14. Ukai Y, Kuroiwa M, Kurihara N, Naruse H, Homma T, Maki H, et al. Contributions of yap1 mutation and subsequent atrf upregulation to voriconazole resistance in Aspergillus flavus. Antimicrob Agents Chemother 2018;62(11): e01216-18.
15. Siopi M, Pournaras S, Meletiadis J. Comparative evaluation of sensititre yeastone and clsi m38-a2 reference method for antifungal susceptibility testing of Aspergillus spp. against Echinocandins. J Clin Microbiol 2017;55:1714-1719.
16. Sharma S, Yenigalla BM, Naidu SK, Pidakala P. Primary cutaneous aspergillosis due to Aspergillus tamarii in an immunocompetent host. BMJ Case Rep 2013;2013:010128.
17. Rudramurthy SM, Paul RA, Chakrabarti A, Mouton JW, Meis JF. Invasive aspergillosis by Aspergillus flavus: epidemiology, diagnosis, antifungal resistance, and management. J Fungi (Basel) 2019;5: E55.
18. Kiakojori K, Bagherpour Jamnani N, Khafri S, Mahdavi Omran S. Assessment of response to treatment in patients with otomycosis. Iran J Otorhinolaryngol 2018;30:41-47.
19. Taghizadeh-Armaki M, Hedayati MT, Ansari S, Omran SM, Saber S, Rafati H, et al. Genetic diversity and in vitro antifungal susceptibility of 200 clinical and environmental Aspergillus flavus isolates. Antimicrob Agents Chemother 2017;61(5): e00004-17.
20. Rudramurthy SM, Seyedmousavi S, Dhaliwal M, Chakrabarti A, Meis JF, Mouton JW. Pharmacodynamics of voriconazole against wild-type and azole-resistant Aspergillus flavus isolates in a nonneutropenic murine model of disseminated aspergillosis. Antimicrob Agents Chemother 2016;61(1): e01491-16.
21. Mosquera J, Warn P, Morrissey J, Moore C, Gil-Lamaignere C, Denning D. Susceptibility testing of Aspergillus flavus: inoculum dependence with itraconazole and lack of correlation between susceptibility to amphotericin B in vitro and outcome in vivo. Antimicrob Agents Chemother 2001;45:1456-1462.
22. Odds F, Van Gerven F, Espinel-Ingroff A, Bartlett M, Ghannoum M, Lancaster M, et al. Evaluation of possible correlations between antifungal susceptibilities of filamentous fungi in vitro and antifungal treatment outcomes in animal infection models. Antimicrob Agents Chemother 1998;42:282-288.
23. Rodrigues P, Soares C, Kozakiewicz Z, Paterson R, Lima N, Venâncio A. Identification and characterization of Aspergillus flavus and aflatoxins. In Microbiology Book Series – Communicating Current Research and Educational Topics ed A Méndez-Vilas pp. 527– 534 Badajoz: Formatex 2007.
24. Sharma C, Kumar R, Kumar N, Masih A, Gupta D, Chowdhary A. Investigation of multiple resistance mechanisms in voriconazole-resistant Aspergillus flavus clinical isolates from a chest hospital surveillance in Delhi, India. Antimicrob Agents Chemother 2018;62(3): e01928-17.
25. Prencipe S, Siciliano I, Contessa C, Botta R, Garibaldi A, Gullino ML, et al. Characterization of Aspergillus section Flavi isolated from fresh chestnuts and along the chestnut flour process. Food Microbiol 2018;69:159-169.
26. CLSI (2017). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; 3rd ed. CLSI document M38-3rd. Wayne, PA: Clinical and Laboratory Standards Institute.
27. Watanabe S, Kishida H, Okubo A. Efficacy and safety of luliconazole 5% nail solution for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study. J Dermatol 2017;44:753-759.
28. Khodavaisy S, Badali H, Hashemi SJ, Aala F, Nazeri M, Nouripour-Sisakht S, et al. In vitro activities of five antifungal agents against 199 clinical and environmental isolates of Aspergillus flavus, an opportunistic fungal pathogen. J Mycol Med 2016;26:116-121.
29. Tissot F, Agrawal S, Pagano L, Petrikkos G, Groll AH, Skiada A, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 2017;102:433-444.
30. Xavier MO, Oliveira Fde M, Almeida V, Prolla G, Severo LC. Invasive Aspergillus flavus sinusitis: case report in a patient with biphenotypic acute leukemia. Rev Inst Med Trop Sao Paulo 2009;51:57-58.
31. Shokoohi GR, Badali H, Mirhendi H, Ansari S, Rezaei-Matehkolaei A, Ahmadi B, et al. In vitro activities of luliconazole, lanoconazole, and efinaconazole compared with those of five antifungal drugs against melanized fungi and relatives. Antimicrob Agents Chemother 2017;61(11): e00635-17.
32. Todokoro D, Suzuki T, Tamura T, Makimura K, Yamaguchi H, Inagaki K, et al. Efficacy of luliconazole against broad-range filamentous fungi including Fusarium solani species complex causing fungal keratitis. Cornea 2019;38:238-242.
33. Wiederhold NP, Fothergill AW, McCarthy DI, Tavakkol A. Luliconazole demonstrates potent in vitro activity against dermatophytes recovered from patients with onychomycosis. Antimicrob Agents Chemother 2014;58:3553-3555.
34. Hivary S, Fatahinia M, Halvaeezadeh M, Zarei Mahmoudabadi A. The potency of luliconazole against clinical and environmental Aspergillus Nigri complex. Iran J Microbiol 2019;11:510-519.
35. Varotto E, Putti MC, Sgarabotto D, Cecchin D, De Corti F, Beltrame V, et al. Aspergillus flavus disseminated infection in paediatric acute lymphoblastic leukaemia: A case report. Med Mycol: Open Access 2016;3:1-5.
| Files | ||
| Issue | Vol 12 No 2 (2020) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v12i2.2623 | |
| Keywords | ||
| Antifungal susceptibility; Luliconazole; Amphotericin B; Voriconazole; Caspofungin; Aspergillus flavus | ||
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How to Cite
1.
Moslem M, Zarei Mahmoudabadi A. The high efficacy of luliconazole against environmental and otomycosis Aspergillus flavus strains. Iran J Microbiol. 2020;12(2):170-176.
