Klinik Trichosporon spp. izolatlarının dağılımı ve antifungal duyarlılığı: 10 yıllık tek merkez deneyimi

Year 2023, Volume: 48 Issue: 3, 1157 - 1166, 30.09.2023

Hatice Hale Gümüş

https://doi.org/10.17826/cumj.1348790

Abstract

Amaç: Maya benzeri bir basidiomycete olan Trichosporon cinsi, doğada her yerde bulunur ve insan mikrobiyotasının bir parçasıdır. Trichosporon spp. bir zamanlar nadir görülen, ancak son zamanlarda dramatik bir şekilde artan ve ölümcül enfeksiyonlara yol açan opurtunistik bir mantar patojenidir. Bu çalışmanın amacı klinik Trichosporon spp. izolatlarının prevalansını ve antifungal duyarlılıklarını belirlemek ve COVID-19 Pandemisi’nde insidansında bir değişiklik olup olmadığını tespit etmektir.
Gereç ve Yöntem: Bu, 1 Ocak 2013 ile 5 Şubat 2023 tarihleri arasında yürütülen, retrospektif kesitsel tanımlayıcı bir çalışmadır. Trichosporon spp. izole edilmiş olan kültür sonuçları (n=125) tarandı ve uygunluk kriterlerini karşılayanlar (n=77) çalışmaya dahil edildi. Demografik veriler, kültür sonuçları ve antifungal duyarlılık test sonuçları Mikrobiyoloji Laboratuvarı Bilgi Yönetim Sistemi’ndeki kayıtlardan elde edildi.
Bulgular: İzolatların %97.4’ü Trichosporon asahii ve %2.6’sı Trichosporon mucoides idi. En sık izolasyon dönemi COVID-19 Pandemisinde (%19,5) değil, 2016 ve 2019 yılları arasında (%71.4) olduğu tespit edildi. En yaygın örnek türü idrardı (%58.4) ve bunların büyük çoğunluğu (%58.4) Yoğun Bakım Ünitesi’ndeki hastalara aitti. Amfoterisin B MİK değerleri izolatların %68.9'unda ≤1µg/ml idi. Flukonazol ve vorikonazol MİK'leri sırasıyla %20.0 ve %94.8'de ≤1µg/ml idi. İzolatların %59.7'sinde flusitozin için MİK değeri ≥4µg/ml idi. Mikafungin ve kaspofungin MİK'leri sırasıyla izolatların %88,3'ünde ve %92,2'sinde ≥4µg/ml idi. Vorikonazol en güçlü in vitro aktiviteye sahipti ve amfoterisin B beklenenden daha düşük MİK'lere sahipti. Bu durumda vorikonazol ve amfoterisin B'nin kombinasyon tedavisinin yanı sıra, vorikonazol monoterapisi de terapötik bir seçenek olabilir.
Sonuç: Klinik örneklerden izole edilen Trichosporon türleri ve bunların antifungal duyarlılıkları coğrafi bölgeye ve anatomik bölgeye bağlı olarak değişmektedir. Lokal verilerin belirlenmesi hem bu hastaların yönetimine hem de sürveyans çalışmalarına katkı sağlayacaktır.

Keywords

Trichosporon asahii, mantar enfeksiyonu, maya, antifungal duyarlılık, antifungal direnç, vorikonazol, fungemi, COVID-19.

Project Number

Yok

Distribution and antifungal susceptibility of clinical Trichosporon spp. isolates: 10 years of single-center experience

Abstract

Purpose: The genus Trichosporon, which is a yeast-like basidiomycete, is ubiquitous in nature and a part of human microbiota. It’s an oppurtunistic fungal pathogen, which was once rare, but increasing dramatically recently, leading to fatal infections. The aim of this study was to determine the prevalence, and antifungal susceptibility of clinical Trichosporon spp. isolates, and to determine whether there was a change in incidence during the COVID-19 Pandemic.
Materials and Methods: This was a retrospective cross-sectional descriptive study, conducted between January 1, 2013 and February 5, 2023. Cultures which Trichosporon spp. isolated (n=125) were screened, and those met the eligibility criteria were included (n=77). Identification, antifungal susceptibility test results, age, gender records were identified from Microbiology Laboratory Information Management System.
Results: 97.4% of the isolates were Trichosporon asahii, and 2.6% were Trichosporon mucoides. The most frequent isolation period was the 2016 and 2019 year group (71.4%), not during the COVID-19 Pandemics (19.5%). The most common sample type was urine (58.4%), of whom predominantly (58.4%) hospitalized in the Intensive Care Unit. Amphotericin B MICs were ≤1µg/ml in 68.9% of the isolates. Fluconazole and voriconazole MICs were ≤1µg/ml in 20.0% and 94.8%, respectively. 59.7% of the isolates had a MIC of ≥4µg/ml for flucytosine. Micafungin and caspofungin MICs were ≥4µg/ml in 88.3% and 92.2% of the isolates, respectively. Voriconazole had the strongest in vitro activity, and amphotericin B had lower MICs than expected. The combination therapy of voriconazole and amphotericin B could be a therapeutic option in this setting, as well as monotherapy of voriconazole.
Conclusion: Trichosporon spp. isolated in clinical specimens and their antifungal susceptibility depend on the geographic region and the anatomic site. Identifying local data will contribute to both the management of these patients, and surveillance studies.

Keywords

Trichosporon asahii, identification, fungal infection, rare yeast, antifungal susceptibility, antifungal resistance, voriconazole, fungaemia, COVID-19.

Supporting Institution

Yok

Project Number

Yok

Thanks

I thank to Prof. Dr. Akgün Yaman and Ass. Prof. Dr. Filiz Kibar for supporting me, and for the management of the Microbiology Laboratory over than ten years. And also thank to Ass. Prof. İlker Ünal for helping with the statistical analysis.

References

• Kainz K, Bauer MA, Madeo F, Carmona-Gutierrez D. Fungal infections in humans: the silent crisis. Microb Cell. 2020;7:143-5.
• Vitiello A, Ferrara F, Boccellino M, Ponzo A, Cimmino C, Comberiati et al. Antifungal drug resistance: An emergent health threat. Biomedicines. 2023;11:1063.
• Schoch CL, Ciufo S, Domrachev M, Hotton CL, Kannan S, Khovanskaya R et al. NCBI Taxonomy: a comprehensive update on curation, resources and tools. Database (Oxford). 2020:baaa062.
• Francisco EC, Hagen F. JMM Profile: Trichosporon yeasts: from superficial pathogen to threat for haematological-neutropenic patients. J Med Microbiol. 2022;71:10.
• Guého E, Improvisi L, de Hoog GS, Dupont B. Trichosporon on humans: a practical account. Mycoses. 1994;37:3-10.
• Castano G, Yarrarapu SNS, Mada PK. Trichosporonosis. Treasure Island (FL), StatPearls Publishing, 2023.
• de Almeida Júnior JN, Hennequin C. Invasive Trichosporon infection: a systematic review on a re-emerging fungal pathogen. Front Microbiol. 2016;7:1629.
• Arastehfar A, de Almeida Júnior JN, Perlin DS, Ilkit M, Boekhout T, Colombo AL. Multidrug-resistant Trichosporon species: underestimated fungal pathogens posing imminent threats in clinical settings. Crit Rev Microbiol. 2021;47:679-98.
• Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner et al. Clinical practice guideline for the management of Candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1–50.
• Cagan E, Soysal A, Bakir M. Childhood Candida infections: single center experience. Cukurova Med J. 2015;40:245-51.
• Guo LN, Yu SY, Hsueh PR, Al-Hatmi AMS, Meis JF, Hagen F et al. Invasive infections due to Trichosporon: species distribution, genotyping, and antifungal susceptibilities from a multicenter study in China. J Clin Microbiol. 2019;57:e01505-18.
• Chagas-Neto TC, Chaves GM, Melo AS, Colombo AL. Bloodstream infections due to Trichosporon spp.: species distribution, Trichosporon asahii genotypes determined on the basis of ribosomal DNA intergenic spacer 1 sequencing, and antifungal susceptibility testing. J Clin Microbiol. 2009;47:1074-81.
• Gomes MZ, Mulanovich VE, Jiang Y, Lewis RE, Kontoyiannis DP. Incidence density of invasive fungal infections during primary antifungal prophylaxis in newly diagnosed acute myeloid leukemia patients in a tertiary cancer center, 2009 to 2011. Antimicrob Agents Chemother. 2014;58:865-73.
• Liao Y, Lu X, Yang S, Luo Y, Chen Q, Yang R. Epidemiology and outcome of Trichosporon fungemia: A review of 185 reported cases from 1975 to 2014. Open Forum Infect Dis. 2015;2:ofv141.
• Barbara D, Alexander MD. M27/Reference method for broth dilution antifungal-susceptibility testing of yeasts. Wayne, PA, Clinical and Laboratory Standards Institute, 2023.
• IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.
• Francisco EC, de Almeida Junior JN, de Queiroz Telles F, Aquino VR, Mendes AVA, de Andrade Barberino MGM et al. Species distribution and antifungal susceptibility of 358 Trichosporon clinical isolates collected in 24 medical centres. Clin Microbiol Infect. 2019;25:909.e1-909.e5.
• Hazirolan G, Kocak N, Karagoz A. Sequence-based identification, genotyping and virulence factors of Trichosporon asahii strains isolated from urine samples of hospitalized patients (2011–2016). J Mycol Med. 2018;28:452–6.
• Kalkanci A, Sugita T, Arikan S, Yucesoy M, Ener B, Otag F et al. Molecular identification, genotyping, and drug susceptibility of the basidiomycetous yeast pathogen Trichosporon isolated from Turkish patients. Med Mycol. 2010;48:141-6.
• Tepe D, Aksoy F, Yilmaz G, Tosun I, Ozkaya E, Kaya S. Fungemia due to rare yeasts other than Candida: 10 years of single-center experience. Mediterr J Infect Microb Antimicrob. 2023;12:9.
• Arabatzis M, Abel P, Kanellopoulou M, Adamou D, Alexandrou-Athanasoulis H, Stathi A et al. Sequence-based identification, genotyping and EUCAST antifungal susceptibilities of Trichosporon clinical isolates from Greece. Clin Microbiol Infect. 2014;20:777-83.
• Francisco EC, de Almeida Junior JN, Queiroz-Telles F, Aquino VR, Mendes AVA, de Oliveira Silva M et al. Correlation of Trichosporon asahii genotypes with anatomical sites and antifungal susceptibility profiles: data analyses from 284 isolates collected in the last 23 years across 24 medical centers. Antimicrob Agents Chemother. 2021;17;65:e01104-20.
• Kangabam N, Nethravathy V. An overview of opportunistic fungal infections associated with COVID-19. 3 Biotech. 2023;13:231.
• Kurra N, Woodard PI, Gandrakota N, Gandhi H, Polisetty SR, Ang SP et al. Opportunistic infections in COVID-19: a systematic review and meta-analysis. Cureus. 2022;14:e23687.
• Nobrega de Almeida J, Francisco EC, Holguın Ruiz A, Cuellar LE, Rodrigues Aquino V, Verena Mendes A et al. Epidemiology, clinical aspects, outcomes and prognostic factors associated with Trichosporon fungaemia: results of an international multicentre study carried out at 23 medical centres. J Antimicrob Chemother. 2021;6:1907-15.
• 26.Yamamoto M, Takakura S, Hotta G, Matsumura Y, Matsushima A, Nagao M et al. Clinical characteristics and risk factors of non-Candida fungaemia. BMC Infect Dis. 2013;13:247.
• Montoya AM, Sánchez González A, Palma-Nicolás JP, Gómez-Treviño A, González JG, González GM. Genotyping, extracellular compounds, and antifungal susceptibility testing of Trichosporon asahii isolated from Mexican patients. Med Mycol. 2015;53:505–11.
• Padovan ACB, Rocha WPS, Toti ACM, Freitas de Jesus DF, Chaves GM, Colombo AL. Exploring the resistance mechanisms in Trichosporon asahii: triazoles as the last defense for invasive trichosporonosis. Fungal Genet Biol. 2019;133:103267.
• Alp S, Gulmez D, Ayaz CM, Arikan-Akdagli S, Akova M. Fungaemia due to rare yeasts in a tertiary care university centre within 18 years. Mycoses. 2020;63:488-93.
• Iturrieta-Gonzalez IA, Padovan ACB, Bizerra FC, Hahn RC, Colombo AL. Multiple species of Trichosporon produce biofilms highly resistant to triazoles and amphotericin B. PLoS One. 2014;9:e109553.
• Di Bonaventura G, Pompilio A, Picciani C, Iezzi M, D’Antonio D, Piccolomini R. Biofilm formation by the emerging fungal pathogen Trichosporon asahii: development, architecture, and antifungal resistance. Antimicrob Agents Chemother. 2006;50:3269-76.
• Escarra F, Lema J, Caracciolo B. Trichosporon asahii sepsis associated with urinary catheter in a pediatric burn unit: 2 case reports. Arch Argent Pediatr. 2017;115:e311–4.
• Urs TA, Kadiyala V, Deepak S, Karthik MK. Catheter associated urinary tract infections due to Trichosporon asahii. J Lab Physicians. 2018;10:464–70.
• Yayla BD, Mutlu B, Geduk A. Invasive Trichosporon infection: a report of two cases. Klimik Derg. 2018;31:67-70.