Antifungal susceptibility of clinical isolates of Aspergillus spp. in Costa Rica
DOI:
https://doi.org/10.51481/amc.v67i3.1471Keywords:
Antifungal agents, Aspergillus spp., Aspergillosis, microbial sensitivity testAbstract
Introduction: Aspergillosis affects mainly immunosuppressed patients, especially those with neutropenia. A decreased susceptibility of antifungals used in the treatment of this disease has been reported in the last decade. At present, in Costa Rica there is a lack of studies concerning the antifungal activity of clinical Aspergillus isolates. Thus, the purpose of the present investigation was to determine the in vitro susceptibility patterns of clinical Aspergillus fumigatus, A. flavus, A. niger, A. terreus and A. versicolor.
Methods: The susceptibility of 42 Aspergillus spp. to amphotericin B, itraconazole and voriconazole was evaluated using the Clinical and Laboratory Standards Institute broth microdilution M38-A guideline for filamentous fungi.
Results: The mean minimal inhibitory concentration (MIC) for A. fumigatus was 1,64 µg mL-1 for amphotericin B, 1,38 µg mL-1 for itraconazole and 3.52 µg mL-1 for voriconazole, and 33,3 % of the isolates were resistant to voriconazole. For the other species tested, the mean MIC was 7,19 µg mL-1 for amphotericin B, 0,46 µg mL-1 for itraconazole and 1,58 µg mL-1 for voriconazole.
Conclusions: MIC values for amphotericin B and itraconazole of most A. fumigatus isolates were comparable to those of wild-type strains. However, a significant percentage of the isolates were resistant to voriconazole, the first line treatment for aspergillosis. Further, A. flavus, A. niger, A. terreus and A. versicolor demonstrated high MIC values for amphotericin B; thus, it is recommended to performed susceptibility testing in these cases if there is a poor response to therapy.
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References
1. Chowdhary A, Sharma C, Meis JF. Azole-resistant aspergillosis: epidemiology, molecular mechanisms, and treatment. J Infect Dis. 2017; 216:436-444. DOI: 10.1093/infdis/jix210.
2. Cadena J, Thompson GR, Patterson TF. Aspergillosis: Epidemiology, diagnosis, and treatment. Infect Dis Clin. 2021; 35:415-434. DOI: 10.1016/j.idc.2021.03.008.
3. Neofytos, D., Horn, D., Anaissie, E., Steinbach, W., Olyaei, A., Fishman, et al. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients. Clin Infect Dis. 2009; 48: 265-273. DOI: 10.1086/595846.
4. Gonçalves SS, Souza ACR, Chowdhary A, Meis JF, Colombo AL. Epidemiology and molecular mechanisms of antifungal resistance in Candida and Aspergillus. Mycoses. 2016; 59:198-219. DOI: 10.1111/myc.12469.
5. 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. DOI: 10.1111/myc.12759.
6. Berger S, El Chazli Y, Babu AF, Coste AT. Azole resistance in Aspergillus fumigatus: a consequence of antifungal use in agriculture? Front Microbiol. 2017; 8:1024. 10.3389/fmicb.2017.01024.
7. Buil JB, Hagen F, Chowdhary A, Verweij PE, Meis JF. Itraconazole, voriconazole, and posaconazole CLSI MIC distributions for wild-type and azole-resistant Aspergillus fumigatus isolates. J Fungi. 2018; 4:1-9. DOI: 10.3390/jof4030103.
8. Wang HC, Hsieh MI, Choi PC, Wu CJ. Comparison of the Sensititre Yeastone and CLSI M38-A2 microdilution methods in determining the activity of amphotericin B, itraconazole, voriconazole, and posaconazole against Aspergillus species. J Clin Microbiol. 2018; 56: e00780-18. DOI: 10.1128/JCM.00780-18.
9. Borman AM, Fraser M, Palmer MD, Szekely A, Houldsworth M, Patterson Z, Johnson EM. 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. 2017; 3:27-41. DOI: 10.3390/jof3020027.
10. Romero M, Messina F, Marin E, Arechavala A, Depardo R, Walker L, Santiso G. Antifungal resistance in clinical isolates of Aspergillus spp.: when local epidemiology breaks the norm. J Fungi. 2019; 5:41-48. DOI: 10.3390/jof5020041.
11. Bedin Denardi LB, Hoch Dalla-Lana B, Pantella Kunz de Jesus F, Bittencourt Severo C, Santurio JM, Zanette RA, Alves SH. 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. DOI: 10.1016/j.bjid.2017.10.005.
12. Kahle M, Buerge IJ, Hauser A, Muller MD, Poiger T. Azole fungicides: occurrence and fate in wastewater and surface waters. Environ Sci Technol. 2008; 42:7193-7200. DOI: 10.1021/es8009309.
13. Macedo D, Leonardelli F, Gamarra S, Garcia-Effron G. Emergence of triazole resistance in Aspergillus spp. in Latin America. Curr Fungal Infect Rep. 2021; 15:93-103. DOI: 10.1007/s12281-021-00418-6.
14. Ramírez-Muñoz F, Fournier-Leiva ML, Ruepert C, Hidalgo Ardón C. Uso de agroquímicos en el cultivo de papa en Pacayas, Cartago, Costa Rica. Agron. Mesoam. 2014; 25:338-345. DOI: 10.15517/am.v25i2.15441.
15. Resendiz Sharpe A, Mercier T, Lestrade PP, van der Beek MT, von dem Borne PA, Cornelissen JJ, Lagrou K. Prevalence of voriconazole-resistant invasive aspergillosis and its impact on mortality in hematology patients. J Antimicrob Chemother. 2019; 74:2759-2766. DOI: 10.1093/jac/dkz258.
16. Arikan S, Lozano-Chiu M, Paetznick V, Nangia S, Rex JH. Microdilution susceptibility testing of amphotericin B, itraconazole, and voriconazole against clinical isolates of Aspergillus and Fusarium species. J Clin Microbiol. 1999; 37:3946-3951. DOI: 10.1128/JCM.37.12.3946-3951.1999.
17. Ashu EE, Korfanty GA, Samarasinghe H, Pum N, You M, Yamamura D, Xu J. Widespread amphotericin B-resistant strains of Aspergillus fumigatus in Hamilton, Canada. Infect Drug Resist. 2018; 1549-1555. DOI: 10.2147/IDR.S170952.
18. Perlin DS, Rautemaa Richardson R, Alastruey Izquierdo A. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis. 2017; 17: e383-e392. DOI: 10.1016/S1473-3099(17)30316-X.
19. Carolus H, Pierson S, Lagrou K, Van Dijck P. Amphotericin B and other polyenes-discovery, clinical use, mode of action and drug resistance. J Fungi. 2020; 6:321- 342. DOI: 10.3390/jof6040321.
20. Vahedi Shahandashti R, Dietl AM, Binder U, Nagl M, Würzner R, Lass Flörl C. Aspergillus terreus and the interplay with amphotericin B: from resistance to tolerance? Antimicrob Agents Chemother. 2022; 66:02274-21. DOI: 10.1128/aac.02274-21.
21. Jing R, Yang WH, Xiao M, Li Y, Zou GL, Wang CY, Hsueh PR. Species identification and antifungal susceptibility testing of Aspergillus strains isolated from patients with otomycosis in northern China. J Microbiol Immunol Infect. 2022; 55:282-290. DOI: 10.1016/j.jmii.2021.03.011.
22. Kidd SE, Crawford LC, Halliday CL. Antifungal susceptibility testing and identification. Infect Dis Clin North Am. 2021; 35:313-339. DOI: 10.1016/j.idc.2021.03.004.
23. Won EJ, Choi MJ, Shin JH, Park YJ, Byun SA, Jung JS, Suh SP. Diversity of clinical isolates of Aspergillus terreus in antifungal susceptibilities, genotypes and virulence in Galleria mellonella model: comparison between respiratory and ear isolates. PLoS One. 2017; 12: e0186086. DOI: 10.1371/journal.pone.0186086.
24. Heo MS, Shin JH, Choi MJ, Park YJ, Lee HS, Koo SH, Ryang DW. Molecular identification and amphotericin B susceptibility testing of clinical isolates of Aspergillus from 11 hospitals in Korea. Ann Lab Med. 2015; 35:602-606. DOI: 10.3343/alm.2015.35.6.602.
25. Pfaller MA, Messer SA, Hollis RJ, Jones RN. Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates of Aspergillus spp. and other filamentous fungi: report from SENTRY Antimicrobial Surveillance Program, 2000. Antimicrob Agents Chemother. 2002; 46:1032-1037. DOI: 10.1128/AAC.46.4.1032-1037.2002.
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