First report of amphotericin B resistant Candida haemulonii isolated from the ICU of a referral hospital in Indonesia
Abstract
Background and Objectives: Amphotericin B is a broad-spectrum antifungal agent commonly used to treat Candida haemulonii infection. C. haemulonii was isolated from patients reported to be intrinsically resistant to amphotericin B, encoded by the ERG2 and ERG11 genes. However, there have been limited studies concerning amphotericin B-resistant C. haemulonii in Indonesia. The objective of this study is to explore the phenotypic and genotypic characteristics (ERG2 and ERG11) of C. haemulonii isolated from the ICU of a referral hospital in Indonesia.
Materials and Methods: Identification and susceptibility tests were conducted using VITEK2. Thereafter, DNA was extracted and amplified using conventional PCR followed by DNA sequencing (Sanger method).
Results: The results of the phenotypic susceptibility test showed that all C. haemulonii were resistant to amphotericin B. ERG2 and ERG11 sequences showed the same amino acid sequence and corresponded to references that are resistant to amphotericin B.
Conclusion: The resistant properties of C. haemulonii against amphotericin B found in this study require further exploration, including comparing resistant and sensitive C. haemulonii to amphotericin B. In addition, it is necessary to analyze other genes besides ERG2 and ERG11.
2. Aslan N, Yildizdas D, Alabaz D, Horoz OO, Yontem A, Kocabas E. Invasive Candida infections in a pediatric intensive care unit in Turkey: Evaluation of an 11-Year period. J Pediatr Intensive Care 2020; 9: 21-26.
3. Kim EJ, Lee E, Kwak YG, Yoo HM, Choi JY, Kim SR, et al. Trends in the epidemiology of candidemia in intensive care units from 2006 to 2017: Results from the Korean National Healthcare-Associated Infections Surveillance System. Front Med (Lausanne) 2020; 7: 606976.
4. Matoa G, Muñoz JS, Oñate J, Pallares CJ, Hernández C, Villegas MV. Epidemiology of Candida isolates from intensive care units in Colombia from 2010 to 2013. Rev Iberoam Micol 2017; 34: 17-22.
5. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of Candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016; 62(4): e1-50.
6. Francisco EC, de Jong AW, Colombo AL. Candida haemulonii species complex: A Mini-review. Mycopathologia 2023; 188: 909-917.
7. Coles M, Cox K, Chao A. Candida haemulonii: An emerging opportunistic pathogen in the United States? IDCases 2020; 21: e00900.
8. Monegro AF, Muppidi V, Regunath H. Hospital-Acquired infections [Internet]. StatPearls. StatPearls Publishing, Treasure Island (FL); 2023 [cited 2023 Jul 30]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441857/
9. Piedrahita CT, Cadnum JL, Jencson AL, Shaikh AA, Ghannoum MA, Donskey CJ. Environmental surfaces in healthcare facilities are a potential source for transmission of Candida auris and other Candida species. Infect Control Hosp Epidemiol 2017; 38: 1107-1109.
10. Espinoza LC, Sosa L, Granda PC, Bozal N, Díaz-Garrido N, Chulca-Torres B, et al. Development of a topical amphotericin B and bursera graveolens essential oil-loaded gel for the treatment of dermal candidiasis. Pharmaceuticals (Basel) 2021; 14: 1033.
11. Osa S, Tashiro S, Igarashi Y, Watabe Y, Liu X, Enoki Y, et al. Azoles versus conventional amphotericin B for the treatment of candidemia: A meta-analysis of randomized controlled trials. J Infect Chemother 2020; 26: 1232-1236.
12. Lima SL, Francisco EC, de Almeida Júnior JN, Santos DWCL, Carlesse F, Queiroz-Telles F, et al. Increasing prevalence of multidrug-resistant Candida haemulonii species complex among all yeast cultures collected by a reference laboratory over the past 11 years. J Fungi (Basel) 2020; 6: 110.
13. Ahmad S, Joseph L, Parker JE, Asadzadeh M, Kelly SL, Meis JF, et al. ERG6 and ERG2 are Major targets conferring reduced susceptibility to amphotericin B in clinical Candida glabrata isolates in Kuwait. Antimicrob Agents Chemother 2019; 63(2): e01900-18.
14. Costa-de-oliveira S, Rodrigues AG. Candida albicans antifungal resistance and tolerance in bloodstream infections: The triad yeast-host-antifungal. Microorganisms 2020; 8: 154.
15. McGowan KL (2015). Specimen collection, transport, and processing: Mycology. In: Manual of Clinical Microbiology. Ed, HJ James, AP Michael, CC Karen, F Guido, LL Marie, SR Sandra, WW David. ASM Press. Washington DC, Pp. 1944-1954.
16. Riedel S, Morse SA, Mietzner T, Miller S (2019). Medical Mycology. In: Jawetz, Melnick & Adelberg’s Medical Microbiology. 28th Ed. McGraw-Hill Education. United States.
17. Melhem MSC, Bertoletti A, Lucca HR, Silva RB, Meneghin FA, Szeszs MW. Use of the VITEK 2 system to identify and test the antifungal susceptibility of clinically relevant yeast species. Braz J Microbiol 2014; 44: 1257-1266.
18. QIAGEN (2016). Protocol for Yeast (e.g., Cultured Candida spp.). In: QIAamp DNA Mini and Blood Mini Handbook. 5th ed. 1-72.
19. García-Alegría AM, Anduro-Corona I, Pérez-Martínez CJ, Corella-Madueño MA, Rascón-Durán ML, Astiazaran-Garcia H. Quantification of DNA through the nanodrop spectrophotometer: Methodological validation using standard reference material and sprague dawley rat and human DNA. Int J Anal Chem 2020; 2020: 8896738.
20. Rosana Y, Lusiana DIG, Yasmon A. Genetic characterization of diphtheria tox B to evaluate vaccine efficacy in Indonesia. Iran J Microbiol 2022; 14: 606-610.
21. Hou X, Xiao M, Chen SCA, Wang H, Cheng JW, Chen XX, et al. Identification and antifungal susceptibility profiles of Candida haemulonii species complex clinical isolates from a multicenter study in China. J Clin Microbiol 2016; 54: 2676-2680.
22. Ramos LS, Figueiredo-Carvalho MH, Barbedo LS, Ziccardi M, Chaves AL, Zancopé-Oliveira RM, et al. Candida haemulonii complex: Species identification and antifungal susceptibility profiles of clinical isolates from Brazil. J Antimicrob Chemother 2015; 70: 111-115.
23. Zhang H, Niu Y, Tan J, Liu W, Sun M-A, Yang E, et al. Global screening of genomic and transcriptomic factors associated with phenotype differences between multidrug-resistant and -susceptible Candida haemulonii strains. mSystems 2019; 4(6): e00459-19.
24. Gade L, Muñoz JF, Sheth M, Wagner D, Berkow EL, Forsberg K, et al. Understanding the emergence of multidrug-resistant Candida: Using Whole-Genome sequencing to describe the population structure of Candida haemulonii species complex. Front Genet 2020; 11: 554.
25. Ruiz-Baca E, Arredondo-Sánchez RI, Corral-Pérez K, López-Rodríguez A, Meneses-Morales I, Ayala-García VM, et al. (2021). Molecular mechanisms of resistance to antifungals in Candida albicans. In: Advances inCandida albicans. Ed, W Xinhui. IntechOpen.
26. Silva LN, Oliveira SSC, Magalhães LB, Andrade Neto VV, Torres-Santos EC, Carvalho MDC, et al. Unmasking the amphotericin B resistance mechanisms in Candida haemulonii species complex. ACS Infect Dis 2020; 6: 1273-1282.
Files | ||
Issue | Vol 16 No 2 (2024) | |
Section | Short Communication | |
DOI | https://doi.org/10.18502/ijm.v16i2.15363 | |
Keywords | ||
Amphotericin B; Candida; Environment; Gene; Healthcare; Resistance |
Rights and permissions | |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |