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Communication

An Autochthonous Susceptible Candida auris Clade I Otomycosis Case in Iran

by
Bahram Ahmadi
1,
Behrouz Naeimi
1,
Mohammad Javad Ahmadipour
2,
Hamid Morovati
3,
Theun de Groot
4,5,
Bram Spruijtenburg
4,5,
Hamid Badali
6,* and
Jacques F. Meis
5,7,*
1
Department of Medical Laboratory Sciences, Faculty of Paramedical, Bushehr University of Medical Sciences, Bushehr 75187-59577, Iran
2
Department of Ear, Nose & Throat (ENT), Dey Clinic, Bushehr 75187-59577, Iran
3
Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
4
Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, 6532 SZ Nijmegen, The Netherlands
5
Center of Expertise for Mycology, Radboud University Medical Center/Canisius-Wilhelmina Hospital, 6532 SZ Nijmegen, The Netherlands
6
Department of Molecular Microbiology & Immunology, South Texas Center for Emerging Infectious Diseases, The University of Texas, San Antonio, TX 78249, USA
7
Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Excellence Center for Medical Mycology (ECMM), University of Cologne, 50923 Cologne, Germany
*
Authors to whom correspondence should be addressed.
J. Fungi 2023, 9(11), 1101; https://doi.org/10.3390/jof9111101
Submission received: 11 October 2023 / Revised: 7 November 2023 / Accepted: 8 November 2023 / Published: 11 November 2023
(This article belongs to the Special Issue Genomic Epidemiology of Fungal Diseases)
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Abstract

:
Candida auris is a newly emerging multidrug-resistant fungal pathogen considered to be a serious global health threat. Due to diagnostic challenges, there is no precise estimate for the prevalence rate of this pathogen in Iran. Since 2019, only six culture-proven C. auris cases have been reported from Iran, of which, five belonged to clade V and one to clade I. Herein, we report a case of otomycosis due to C. auris from 2017 in a 78-year-old man with diabetes mellitus type II without an epidemiological link to other cases or travel history. Short tandem repeat genotyping and whole genome sequencing (WGS) analysis revealed that this isolate belonged to clade I of C. auris (South Asian Clade). The WGS single nucleotide polymorphism calling demonstrated that the C. auris isolate from 2017 is not related to a previously reported clade I isolate from Iran. The presence of this retrospectively recognized clade I isolate also suggests an early introduction from other regions or an autochthonous presence. Although the majority of reported C. auris isolates worldwide are resistant to fluconazole and, to a lesser extent, to echinocandins and amphotericin B, the reported clade I isolate from Iran was susceptible to all antifungal drugs.

1. Introduction

Candida auris is a newly described emerging multidrug-resistant yeast which is regarded as a serious global health threat [1,2,3,4]. This pathogen was initially described in a Japanese patient with otitis externa in 2009 [5], followed by outbreaks in India in 2012–2014 [6] and a global emergence from 2015 onwards [2,3,7,8]. The recent studies of C. auris have pointed to environmental and/or animal niches [9,10,11]. COVID-19 infection, diabetes mellitus (DM), immunosuppression, broad-spectrum antimicrobial use, and corticosteroids are among the main risk factors for C. auris infections [3,11,12]. Compared to other pathogenic fungi, C. auris has unique abilities such as long-term persistence on inanimate surfaces and protracted cross-transmission between patients [13]. Furthermore, a significant percentage of C. auris isolates have been shown to be resistant to or have reduced susceptibility to registered antifungal drugs [14]. Based on genomic analyses, C. auris isolates have been allocated to five geographical clades (I to V): the South Asian, East Asian, African, South American, and Iranian clade, respectively [8,15], while an additional clade (VI), Indomalaya, was recently reported in Singapore [16]. These distinct C. auris clades evolved seemingly simultaneously at independent geographical locations and display both genetic and phenotypic diversity [8]. While clades I, III, and IV are responsible for the ongoing outbreaks of invasive and multidrug-resistant infections, clades II and V consist primarily of cases of ear infections, are often susceptible to antifungal drugs, and have not been associated with outbreaks [15,17]. Here, we describe a case of C. auris otomycosis of a patient in Bushehr, Iran, compare this with earlier reported cases, and performed susceptibility testing on the isolate.

2. Case Presentation

In April 2017, a 78-year-old man with discharge from and itching of the external ear canal was admitted to an ear, nose, and throat specialist in Bushehr, a coastal city at the Persian Gulf, Iran. He had diabetes mellitus type II for more than 10 years as the only predisposing factor. With the clinical suspicion of a fungal infection, the ear discharge was submitted for investigation. Round and oval cells were observed with microscopic examination with 10% potassium hydroxide (KOH). The specimen was cultured on Sabouraud’s dextrose agar supplemented with chloramphenicol (SDA, Merck, Darmstadt, Germany), and incubated at 35 °C for 48 h. White-to-cream, smooth, yeast-like colonies were germ tube-negative and thus identified as non-albicans Candida species. The patient was managed with topical empirical therapy with betamethasone 1% for the itching and inflammation of the external ear canal, as well as hydrogen peroxide 1% and ciprofloxacin 0.3%. The patient completely improved after one week with this regimen and did not receive specific antifungal therapy.

3. Materials and Methods

Retrospective molecular identification was performed 5 years later with ITS rDNA sequencing [18,19] and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF; Bruker, Bremen, Germany) identifying the yeast as C. auris. For DNA isolation, the isolate was resuspended in 700 µL MagNA Pure bacteria lysis buffer and MagNA Lyser green beads and lysed with the MagNA Lyser system (all Roche Diagnostics GmbH, Mannheim, Germany). Subsequent DNA extraction and purification was performed with the MagNA Pure 96 instrument and the MagNA Pure DNA and Viral NA Small Volume kit (Roche Diagnostics) [20,21]. The ITS rDNA sequence of the isolate (MRL32) was deposited in GenBank under accession number OQ740733. In vitro antifungal susceptibility testing was performed by broth microdilution according to the Clinical and Laboratory Standards Institute (CLSI) standard M27-S4 [22]. In addition, short tandem repeat (STR) genotyping was performed as previously described [20]. For whole-genome sequencing (WGS), genomic libraries were prepared and sequenced with the Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA) with 2- by 150-bp paired-end read mode at Eurofins Genomics (Ebersberg, Germany). Read data were extracted from the SRA database (Supplementary Table S1). Reads were aligned and variant calling was performed as previously described [23]. All raw read data generated in this study were deposited under BioProject accession number PRJNA1002104.

4. Results

The STR dendrogram with the representatives of all known C. auris clades showed that MRL32 was phylogenetically distinct from other Iranian C. auris isolates belonging to the local clade V, clustered with the South Asian clade (I), but had a different genotype than the previously reported Iranian clade I isolate (CSF1020) (Figure 1).
To determine the genetic distance between both Iranian clade I isolates, WGS single nucleotide polymorphism (SNP) calling was performed on both isolates and compared with other clades (Supplementary Table S1). The WGS SNP analysis confirmed that both Iranian isolates belonged to clade I and demonstrated that they were separated by 866 SNPs (Figure 2).
The minimum inhibitory concentrations of MRL32 were as follows: amphotericin B (1 μg/mL), fluconazole (8 μg/mL), itraconazole (0.5 μg/mL), posaconazole (0.25 μg/mL), voriconazole (0.125 μg/mL), isavuconazole (0.125 μg/mL), miconazole (4 μg/mL), caspofungin (0.25 μg/mL), anidulafungin (0.063 μg/mL), and micafungin (0.125 μg/mL). While the previously reported clade I fluconazole-resistant isolate (CSF1020) from Iran grouped with other fluconazole-resistant isolates from India, the fluconazole-susceptible isolate MRL32 did not group with any fluconazole-resistant isolates. In agreement with the phenotypic susceptibility testing, the visual alignment inspection with JBrowse of the resistance associated genes ERG11, TAC1b, and FKS1 showed the absence of unique mutations in MRL32 when compared to the resistant isolates. The previously reported fluconazole-resistant isolate from Iran was found to harbor the ERG11Y132F substitution.
The patient characteristics and diagnostic details of the present case and previously published Iranian Candida auris cases are depicted in Table 1.

5. Discussion

C. auris is an emerging multidrug-resistant pathogen becoming a global threat due to its potential for nosocomial spreading [28] during both the pre-COVID and COVID-19 era [11,29]. A systematic review and meta-analysis showed that the prevalence of C. auris among COVID-19 patients having DM was 52.9% [12] and that the pooled prevalence of C. auris infection among COVID-19 patients was 5.7%. DM is among the main predisposing factors of C. auris infection. Here, we report a retrospectively detected case from 2017 in a 78-year-old man with otitis externa caused by a susceptible C. auris. Up until now, the prevalence of C. auris in Iran was low [15,24,25,26,27]. The main reason for this low prevalence rate may be the inability to detect the pathogen and the lack of standard diagnostic methods. DNA sequencing is considered the gold standard method for identifying C. auris. However, diagnostic allele-specific PCR, STR typing, or whole-genome sequencing (WGS) are necessary for categorizing the geographical clades [3,20,30]. We show that the first Iranian C. auris from 2017 was actually from clade I. Retrospective studies from France also identified an early clade I introduction in 2007 [31]. The reported Iranian C. auris isolates from clade V had a similar susceptibility pattern as this clade I isolate from 2017 [15,24,25,26,27].
Our case is the sixth reported case of C. auris in Iran. The geographical distribution of C. auris cases in Iran is as follows: two cases from Babol in the north of Iran [15,24], one case from Isfahan in the center of Iran [26], one case from Shiraz (South of Iran) [27], one case from Tehran [25], and the present case from a Persian Gulf coastal city in the southwest of Iran, Bushehr. Most isolates belonged to the unique Iranian clade V, except the case from Tehran and the present one, which were both allocated to clade I. The clade V isolates differed by less than 100 single nucleotide polymorphisms (SNPs) intra-clade and by more than 200,000 SNPs between the known clades [15]. The antifungal susceptibility testing showed that two isolates (from Babol and Isfahan) were resistant to fluconazole. The in silico analysis of WGS reads indicated that the mechanisms of the underlying drug resistance in these two isolates was due to mutations in the TAC1b and ERG11 genes. The first reported South Asian (Clade I) C. auris isolate from Iran in 2021 was from an invasive infection linked to travel to the Indian subcontinent and was fluconazole-resistant [25]. Genetic analysis demonstrated the frequently reported ERG11Y132F substitution which is known to induce resistance [32].
Our patient is the oldest and the second male case of C. auris in Iran. Otitis externa was the most common presentation of C. auris (three out of six) in Iran. The case from Shiraz had epidermal dysplasia, while the Tehran case involved meningitis with C. auris in a 30-month-old male infant [25]. Earache, itching, discharge from the ear canal, and inflammation are the most common clinical signs and symptoms reported in Iranian C. auris cases. Among the patients with clade V isolates, none traveled abroad until the diagnosis of the infection, while the 30-month-old male infant from Tehran with clade I was hospitalized in Pakistan (Table 1).
Distinct C. auris clades evolved seemingly simultaneously at independent geographical locations and display both genetic and phenotypic diversity [8]. The emergence and persistence of four genomic C. auris clades in a single country without epidemiological links have been described in the USA [33], Canada [34], and Algeria [35], while the UK [36] and South Africa [37] reported three circulating clades. Many other countries, including Iran, have reported the presence of two clades.
To investigate the phylogenetic relationship between this isolate and the previously reported Iranian clade I isolate, WGS SNP analysis was performed on both. Due to substantial SNP differences (>800) between the isolates, it can be concluded that the introduction of the second clade I isolate was independent from the first isolate. The first isolate displayed low SNP differences when compared to other clinical-fluconazole resistant isolates, as is frequently observed for C. auris [21], and also correlated with previous hospitalization in Pakistan. Importantly, the 2017 clade I isolate from Iran did not group with the fluconazole-resistant isolates. In agreement, the fluconazole MIC was found to be wildtype, in contrast to most isolates from clade I that are fluconazole-resistant [38]. As there was no travel history of this patient from Bushehr, the mode of the introduction of this yeast in Iran remains to be determined. A study of an autochthonous clade I isolate in a Latin American country, where clade IV is most commonly encountered, also showed a large SNP difference and fluconazole susceptibility compared to the original clade I from the Indian subcontinent [39].
To conclude, misdiagnosis and the application of conventional diagnostic methods lead to a lack of data about C. auris cases in Iran. We found a second clade I isolate in Iran, which was not related to the previous clade I isolate. The addition of this and earlier reports to the literature may motivate researchers to focus on the detection of this pathogen.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/jof9111101/s1, Table S1: Overview of sequence read archive (SRA) numbers of control strains.

Author Contributions

Conceptualization, B.A. and H.B.; formal analysis, B.N., M.J.A. and B.S.; investigation, H.M. and T.d.G.; project administration, H.B.; resources, B.N., M.J.A. and J.F.M.; writing—original draft, B.A., H.B. and J.F.M.; writing—review and editing, B.A., B.N., M.J.A., H.M., T.d.G., B.S., H.B. and J.F.M. All authors have read and agreed to the published version of the manuscript.

Funding

This work was financially supported by Bushehr University of Medical Sciences (grant no. 20/71/119), Bushehr, Iran.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of the Bushehr University of Medical Sciences (IR.BPUMS.REC.1399.077).

Informed Consent Statement

Informed consent was obtained from the patient to include clinical details in the manuscript.

Data Availability Statement

The genomic data from the present study are submitted under Bioproject number PRJNA1002104.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Meis, J.F.; Chowdhary, A. Candida auris: A global fungal public health threat. Lancet Infect. Dis. 2018, 18, 1298–1299. [Google Scholar] [CrossRef] [PubMed]
  2. Hyde, K.D.; Al-Hatmi, A.M.; Andersen, B.; Boekhout, T.; Buzina, W.; Dawson, J.T.L.; Eastwood, D.C.; Gareth Jones, E.B.; de Hoog, S.; Kang, Y.; et al. The world’s ten most feared fungi. Fungal Diver. 2018, 93, 161–194. [Google Scholar]
  3. Chowdhary, A.; Jain, K.; Chauhan, N. Candida auris Genetics and Emergence. Annu. Rev. Microbiol. 2023, 77, 583–602. [Google Scholar] [CrossRef]
  4. Sharma, C.; Kadosh, D. Perspective on the origin, resistance, and spread of the emerging human fungal pathogen Candida auris. PLoS Pathog. 2023, 19, e1011190. [Google Scholar] [CrossRef]
  5. 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, 41–44. [Google Scholar] [CrossRef]
  6. Chowdhary, A.; Anil Kumar, V.; Sharma, C.; Prakash, A.; Agarwal, K.; Babu, R.; Dinesh, K.R.; Karim, S.; Singh, S.K.; Hagen, F.; et al. Multidrug-resistant endemic clonal strain of Candida auris in India. Eur. J. Clin. Microbiol. Infect. Dis. 2014, 33, 919–926. [Google Scholar] [CrossRef]
  7. Vinayagamoorthy, K.; Pentapati, K.C.; Prakash, H. Prevalence, risk factors, treatment and outcome of multidrug resistance Candida auris infections in Coronavirus disease (COVID-19) patients: A systematic review. Mycoses. 2022, 65, 613–624. [Google Scholar] [CrossRef]
  8. Lockhart, S.R.; Etienne, K.A.; Vallabhaneni, S.; Farooqi, J.; Chowdhary, A.; Govender, N.P.; Colombo, A.L.; Calvo, B.; Cuomo, C.A.; Desjardins, C.A.; et al. Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses. Clin. Infect. Dis. 2017, 64, 134–140. [Google Scholar] [CrossRef]
  9. Arora, P.; Singh, P.; Wang, Y.; Yadav, A.; Pawar, K.; Singh, A.; Padmavati, G.; Xu, J.; Chowdhary, A. Environmental isolation of Candida auris from the coastal wetlands of Andaman Islands, India. mBio 2021, 12, e03181-20. [Google Scholar] [CrossRef] [PubMed]
  10. Yadav, A.; Wang, Y.; Jain, K.; Panwar, V.A.R.; Kaur, H.; Kasana, V.; Xu, J.; Chowdhary, A. Candida auris in Dog Ears. J. Fungi 2023, 9, 720. [Google Scholar] [CrossRef]
  11. Garcia-Bustos, V.; Cabañero-Navalon, M.D.; Ruiz-Gaitán, A.; Salavert, M.; Tormo-Mas, M.Á.; Pemán, J. Climate change, animals, and Candida auris: Insights into the ecological niche of a new species from a One Health approach. Clin. Microbiol. Infect. 2023, 29, 858–862. [Google Scholar] [CrossRef]
  12. Vaseghi, N.; Sharifisooraki, J.; Khodadadi, H.; Nami, S.; Safari, F.; Ahangarkani, F.; Meis, J.F.; Badali, H.; Morovati, H. Global Prevalence and Subgroup Analyses of Coronavirus Disease (COVID-19) Associated Candida auris infections (CACa): A Systematic Review and Meta-Analysis. Mycoses 2022, 65, 683–703. [Google Scholar] [CrossRef] [PubMed]
  13. Dire, O.; Ahmad, A.; Duze, S.; Patel, M. Survival of Candida auris on environmental surface materials and low-level resistance to disinfectant. J. Hosp. Infect. 2023, 137, 17–23. [Google Scholar] [CrossRef] [PubMed]
  14. Chowdhary, A.; Prakash, A.; Sharma, C.; Kordalewska, M.; Kumar, A.; Sarma, S.; Tarai, B.; Singh, A.; Upadhyaya, G.; Upadhyay, S.; et al. A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009–2017) in India: Role of the ERG11 and FKS1 genes in azole and echinocandin resistance. J. Antimicrob. Chemother. 2018, 73, 891–899. [Google Scholar] [CrossRef]
  15. Spruijtenburg, B.; Badali, H.; Abastabar, M.; Mirhendi, H.; Khodavaisy, S.; Sharifisooraki, J.; Taghizadeh Armaki, M.; de Groot, T.; Meis, J.F. Confirmation of fifth Candida auris clade by whole genome sequencing. Emerg. Microbes Infect. 2022, 11, 2405–2411. [Google Scholar] [CrossRef]
  16. Suphavilai, C.; Kwan Ki Ko, K.; Lim, K.M.; Tan, M.G.; Boonsimma, P.; Jun Keat Chu, J.; Goh, S.S.; Rajandran, P.; Lee, L.C.; Yuen Tan, K.; et al. Discovery of the sixth Candida auris clade in Singapore. medRxiv 2023. [Google Scholar] [CrossRef]
  17. Jung, J.; Kim, M.J.; Kim, J.Y.; Lee, J.Y.; Kwak, S.H.; Hong, M.J.; Chong, Y.P.; Lee, S.O.; Choi, S.H.; Kim, Y.S.; et al. Candida auris colonization or infection of the ear: A single-center study in South Korea from 2016 to 2018. Med. Mycol. 2020, 58, 124–127. [Google Scholar] [CrossRef]
  18. Aboutalebian, S.; Mahmoudi, S.; Mirhendi, H.; Okhovat, A.; Abtahi, H.; Chabavizadeh, J. Molecular epidemiology of otomycosis in Isfahan revealed a large diversity in causative agents. J. Med. Microbiol. 2019, 68, 918–923. [Google Scholar] [CrossRef]
  19. White, T.J.; Bruns, T.; Lee, S.; Taylor, J. Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics. PCR Protoc. Guide Methods Appl. 1990, 18, 315–322. [Google Scholar]
  20. de Groot, T.; Puts, Y.; Berrio, I.; Chowdhary, A.; Meis, J.F. Development of Candida auris Short Tandem Repeat Typing and Its Application to a Global Collection of Isolates. mBio 2020, 11, e02971-19. [Google Scholar] [CrossRef] [PubMed]
  21. de Groot, T.; Spruijtenburg, B.; Parnell, L.A.; Chow, N.A.; Meis, J.F. Optimization and Validation of Candida auris Short Tandem Repeat Analysis. Microbiol. Spectr. 2022, 10, e0264522. [Google Scholar] [CrossRef]
  22. Clinical and Laboratory Standards Institute. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, 4th ed.; Approved Standard M27 Clinical and Laboratory Standards Institute: Wayne, PA, USA, 2017. [Google Scholar]
  23. Spruijtenburg, B.; Ahmad, S.; Asadzadeh, M.; Alfouzan, W.; Al-Obaid, I.; Mokaddas, E.; Meijer, E.F.J.; Meis, J.F.; de Groot, T. Whole genome sequencing analysis demonstrates therapy-induced echinocandin resistance in Candida auris isolates. Mycoses 2023, 66, 1079–1086. [Google Scholar] [CrossRef] [PubMed]
  24. Armaki, M.T.; Mahdavi Omran, S.; Kiakojuri, K.; Khojasteh, S.; Jafarzadeh, J.; Tavakoli, M.; Badali, H.; Haghani, I.; Shokohi, T.; Taghi Hedayati, M.; et al. First fluconazole-resistant Candida auris isolated from fungal otitis in Iran. Curr. Med. Mycol. 2021, 7, 51–54. [Google Scholar] [CrossRef]
  25. Mirhendi, H.; Charsizadeh, A.; Aboutalebian, S.; Mohammadpour, M.; Nikmanesh, B.; de Groot, T.; Meis, J.F.; Badali, H. South Asian (Clade I) Candida auris meningitis in a paediatric patient in Iran with a review of the literature. Mycoses 2022, 65, 134–139. [Google Scholar] [CrossRef] [PubMed]
  26. Safari, F.; Madani, M.; Badali, H.; Kargoshaie, A.-A.; Fakhim, H.; Kheirollahi, M.; Meis, J.F.; Mirhendi, H. A chronic autochthonous fifth clade case of Candida auris otomycosis in Iran. Mycopathologia 2022, 187, 121–127. [Google Scholar] [CrossRef] [PubMed]
  27. Park, J.; Youssefian, L.; Khodavaisy, S.; Palizban, F.; Tavasoli, A.; Kalamati, E.; Mahmoudi, H.; Balighi, K.; Mesdaghi, M.; Saeidian, A.; et al. Chronic mucocutaneous candidiasis due to Candida auris and non-albicans Candida species in a family with a mild TP63-associated ectodermal dysplasia. J. Invest. Dermatol. 2022, 142, S84. [Google Scholar] [CrossRef]
  28. Ben Abid, F.; Salah, H.; Sundararaju, S.; Dalil, L.; Abdelwahab, A.H.; Salameh, S.; Ibrahim, E.B.; Almaslmani, M.A.; Tang, P.; Perez-Lopez, A.; et al. Molecular characterization of Candida auris outbreak isolates in Qatar from patients with COVID-19 reveals the emergence of isolates resistant to three classes of antifungal drugs. Clin Microbiol Infect. 2023, 29, 1083.e1–1083.e7. [Google Scholar] [CrossRef]
  29. Mulet Bayona, J.V.; Tormo Palop, N.; Salvador García, C.; Guna Serrano, M.D.R.; Gimeno Cardona, C. Candida auris from colonisation to candidemia: A four-year study. Mycoses 2023, 66, 882–890. [Google Scholar] [CrossRef]
  30. Carolus, H.; Jacobs, S.; Lobo Romero, C.; Deparis, Q.; Cuomo, C.A.; Meis, J.F.; Van Dijck, P. Diagnostic Allele-Specific PCR for the Identification of Candida auris Clades. J. Fungi 2021, 7, 754. [Google Scholar] [CrossRef]
  31. Desnos-Ollivier, M.; Fekkar, A.; Bretagne, S. Earliest case of Candida auris infection imported in 2007 in Europe from India prior to the 2009 description in Japan. J. Mycol. Med. 2021, 31, 101139. [Google Scholar] [CrossRef]
  32. Rybak, J.M.; Sharma, C.; Doorley, L.A.; Barker, K.S.; Palmer, G.E.; Rogers, P.D. Delineation of the Direct Contribution of Candida auris ERG11 Mutations to Clinical Triazole Resistance. Microbiol. Spectr. 2021, 9, e0158521. [Google Scholar] [CrossRef] [PubMed]
  33. Chow, N.A.; Gade, L.; Tsay, S.V.; Forsberg, K.; Greenko, J.A.; Southwick, K.L.; Barrett, P.M.; Kerins, J.L.; Lockhart, S.R.; Chiller, T.M.; et al. Multiple introductions and subsequent transmission of multidrug-resistant Candida auris in the USA: A molecular epidemiological survey. Lancet Infect. Dis. 2018, 18, 1377–1384. [Google Scholar] [CrossRef]
  34. De Luca, D.G.; Alexander, D.C.; Dingle, T.C.; Dufresne, P.J.; Hoang, L.M.; Kus, J.V.; Schwartz, I.S.; Mulvey, M.R.; Bharat, A. Four genomic clades of Candida auris identified in Canada, 2012–2019. Med. Mycol. 2022, 60, myab079. [Google Scholar] [CrossRef] [PubMed]
  35. Zerrouki, H.; Ibrahim, A.; Rebiahi, S.A.; Elhabiri, Y.; Benhaddouche, D.E.; de Groot, T.; Meis, J.F.; Rolain, J.M.; Bittar, F. Emergence of Candida auris in intensive care units in Algeria. Mycoses 2022, 65, 753–759. [Google Scholar] [CrossRef]
  36. Borman, A.M.; Szekely, A.; Johnson, E.M. Isolates of the emerging pathogen Candida auris present in the UK have several geographic origins. Med. Mycol. 2017, 55, 563–567. [Google Scholar] [CrossRef]
  37. Naicker, S.D.; Maphanga, T.G.; Chow, N.A.; Allam, M.; Kwenda, S.; Ismail, A.; Govender, N.P. Clade distribution of Candida auris in South Africa using whole genome sequencing of clinical and environmental isolates. Emerg. Microbes Infect. 2021, 10, 1300–1308. [Google Scholar] [CrossRef]
  38. Chow, N.A.; Munoz, J.F.; Gade, L.; Berkow, E.L.; Li, X.; Welsh, R.M.; Forsberg, K.; Lockhart, S.R.; Adam, R.; Alanio, A.; et al. Tracing the Evolutionary History and Global Expansion of Candida auris Using Population Genomic Analyses. mBio 2020, 11, e03364-19. [Google Scholar] [CrossRef] [PubMed]
  39. Nobrega de Almeida, J., Jr.; Brandão, I.B.; Francisco, E.C.; de Almeida, S.L.R.; de Oliveira Dias, P.; Pereira, F.M.; Santos Ferreira, F.; de Andrade, T.S.; de Miranda Costa, M.M.; de Souza Jordão, R.T.; et al. Axillary Digital Thermometers uplifted a multidrug-susceptible Candida auris outbreak among COVID-19 patients in Brazil. Mycoses 2021, 64, 1062–1072. [Google Scholar] [CrossRef]
Jof 09 01101 g001
Figure 1. Short tandem repeat (STR) typing of Candida auris isolates including the current isolate. The UPGMA dendrogram was generated with BioNumerics v7.6, branch lengths indicate similarity, and the currently reported isolate is indicated in bold.
Figure 1. Short tandem repeat (STR) typing of Candida auris isolates including the current isolate. The UPGMA dendrogram was generated with BioNumerics v7.6, branch lengths indicate similarity, and the currently reported isolate is indicated in bold.
Jof 09 01101 g001
Jof 09 01101 g002
Figure 2. Phylogenetic tree based on single nucleotide polymorphisms (SNPs) of 29 Candida auris isolates including all reported clades. Numbers below the branch indicate the number of SNPs. The tree was generated with MEGA11 using the neighbor-joining tree method.
Figure 2. Phylogenetic tree based on single nucleotide polymorphisms (SNPs) of 29 Candida auris isolates including all reported clades. Numbers below the branch indicate the number of SNPs. The tree was generated with MEGA11 using the neighbor-joining tree method.
Jof 09 01101 g002
Table 1. Patient characteristics and diagnostic details of Iranian Candida auris cases.
Table 1. Patient characteristics and diagnostic details of Iranian Candida auris cases.
First IsolateSecond IsolateThird IsolateFourth IsolateFifth IsolateSixth Isolate
[Original reference]
year		[15]
2018		[24]
2021		[25]
2021		[26]
2021		[27]
2022		Current study
Geographical cladeV VIVVI
Demographic
Data		Age (year)144030 months33Teenager78
SexFemaleFemaleMaleFemaleFemaleMale
Underlying diseasesOtitisBilateral otalgiaMeningitisOtitisEpidermal dysplasia (TB63 Genetic variant)Diabetes mellitus
Origin City and ZoneBabol; North of IranBabol; North of IranIsfahan; Center of IranIsfahan; Center of IranShiraz; South of IranBushehr; South-west of Iran
Site of IsolationEar dischargeEar dischargeLP (CSF)Ear discharge- Ear discharge;
- Skin scrapings		Ear discharge
Clinical Signs
and Symptoms		- Right-sided earache;
- Severe itching;
- Hearing loss;
- White-to-creamy discharge from the ear canal;
- Inflammation;
- Redness and tympanic membrane perforation in right ear		- Itching of external ear canal;
- Creamy discharge of ear canal;
- Inflammation (redness and swelling)		- Vomiting;
- Loss of consciousness;
- Frequent seizures		- Right-sided earache;
- Severe itching;
- Hearing loss;
- White-to-creamy discharge from the ear canal;
- Pruritus;
- Otalgia;
- Tinnitus;
- Otorrhea;
- Inflammation;
- Redness in her right ear		- Severe itching;
- Ear discharge		- Itching;
- Ear discharge
Predisposing Factor- No trauma or predisposing factor;
-No travel history		- Repeated ear manipulation;
- Ear eczema;
- No travel history		- Previous hospitalization in Pakistan- No predisposing factor;
- No travel history		- Ichthyosis;
- No travel history		- Diabetes mellitus type 2;
- No travel history
Identification
Methods		Mycological- KOH smear;
- Culture on SDA (white);
- CHROM agar Candida (pink)
- MALDI-TOF MS		- KOH smear;
- Culture on SDA (white);
- CHROM agar Candida (pale pink to dark purple)		- KOH smear;
- Culture on SDA (white to creamy; yeast);
- MALDI-TOF MS		- KOH and Giemsa smear (hyphae and yeasts);
- Culture on SDA
MALDI-TOF MS (filamentous fungi; Aspergillus sp.) (white to creamy; yeast);
- CHROM agar Candida (pink)		- KOH smear;
- Culture on SDA;
- CHROM agar Candida;
- MALDI-TOF MS		- KOH smear (round and oval cells);
- Culture on SDA (white to cream);
- CHROM agar Candida (pale pink to dark purple)
MolecularWGS- PCR of ITS gene region WGS- Multiplex PCR;
- PCR of ITS gene region 		- PCR of beta tubulin gene region;
- PCR of ITS gene region;
- STR genotyping
WGS		- STR genotyping
WGS		- Multiplex PCR of ITS gene region STR genotyping;
-WGS
Reference SequencingITS rDNA
[MK123931.1]		ITS rDNA
[MW019910.1]		ITS rDNA
MZ853742.1		- Beta tubulin gene;
- ITS rDNA
MZ389242.1		NDITS rDNA
OQ740733
Similarity with the Standard/ex-type Isolate99.5% with EU884189.1100% with MH427523.1100% with
MT912579.1		- 99.5% with MT974681.1ND100% with OK625328.1
Antifungal Susceptibility Profile (μg/mL)- Fluconazole: 16;
- Itraconazole: 0.063
- Voriconazole: 0.125;
- Micafungin: 0.031;
- Amphotericin B: 0.5;
- Anidulafungin: 0.016;
- Posaconazole: 0.016;
- Isavuconazole: 0.063		- Fluconazole: ≥32;
- Itraconazole: 0.016
- Voriconazole: 1;
- Micafungin: 0.032;
- Amphotericin B: 0.25;
- Anidulafungin: 0.016;
- Posaconazole: 0.016;
- Isavuconazole: 0.016;
- Ravuconazole: 0.5;
- Ketoconazole: 2;
- Clotrimazole: 2
- Nystatin: 2		- Fluconazole: >64;
Amphotericin B: 1;
- Itraconazole: 0.125;
- Voriconazole: 0.25;
- Clotrimazole: 0.015;
- Nystatin: 8;
- Caspofungin: 0.5;
- Anidulafungin: 1;
- 5-flucytosine: 0.125		- Fluconazole: >64;
- Itraconazole: 0.5;
- Voriconazole: 1;
- Micafungin: 0.015;
- Caspofungin: 0.015;
- Amphotericin B: 1;
- Anidulafungin: 0.125;
- Terbinafine: >16;
- 5-flucytosine: 0.5		- Fluconazole: 1;
- Itraconazole: 0.016;
- Voriconazole: 0.016;
- Micafungin: 0.031;
- Amphotericin B: 0.25;
- Anidulafungin: 0.63;
- Posaconazole: 0.016;
- Isavuconazole: 0.016		- Fluconazole: 8;
- Itraconazole: 0.5;
- Caspofungin: 1;
- Amphotericin B: 1;
- Miconazole: 4
Therapeutic Strategies- Empirical antibacterial therapy:
Cefixime (400 mg/d);
Topical gentamicin
- Antifungal therapy: Topical nystatin (100,000 Units/g);
Terbinafine (250 mg/d)		- Empirical antibacterial therapy:
Ciprofloxacin;
Gentamicin
- Inflammation therapy:
Betamethasone
- Antifungal therapy:
Topical clotrimazole;
Topical miconazole		- Empirical antibacterial therapy:
Meropenem;
Vancomycin
- antiepileptic drugs:
Phenobarbital;
Phenytoin;
Levetiracetam
Inflammation therapy:
IFN-γ
- Antifungal therapy:
Fluconazole (100 mg/kg/d);
IV Liposomal amphotericin B (3 mg/kg/day; i.v);
Oral flucytosine (250 mg/kg/d)		- Empirical antibacterial therapy:
Myxacort;
Bactimide
- Surgery
- Inflammation therapy:
Hydrocortisone-acetic acid otic
- Antifungal therapy:
Topical clotrimazole		ND- Empirical antibacterial therapy:
Topical ciprofloxacin (0.3%)
-Inflammation therapy:
Betamethasone
OutcomeImprovedImprovedNo follow-up availableImprovedImprovedImproved
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MDPI and ACS Style

Ahmadi, B.; Naeimi, B.; Ahmadipour, M.J.; Morovati, H.; de Groot, T.; Spruijtenburg, B.; Badali, H.; Meis, J.F. An Autochthonous Susceptible Candida auris Clade I Otomycosis Case in Iran. J. Fungi 2023, 9, 1101. https://doi.org/10.3390/jof9111101

AMA Style

Ahmadi B, Naeimi B, Ahmadipour MJ, Morovati H, de Groot T, Spruijtenburg B, Badali H, Meis JF. An Autochthonous Susceptible Candida auris Clade I Otomycosis Case in Iran. Journal of Fungi. 2023; 9(11):1101. https://doi.org/10.3390/jof9111101

Chicago/Turabian Style

Ahmadi, Bahram, Behrouz Naeimi, Mohammad Javad Ahmadipour, Hamid Morovati, Theun de Groot, Bram Spruijtenburg, Hamid Badali, and Jacques F. Meis. 2023. "An Autochthonous Susceptible Candida auris Clade I Otomycosis Case in Iran" Journal of Fungi 9, no. 11: 1101. https://doi.org/10.3390/jof9111101

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