Caracterização de Candida spp. isoladas da corrente sanguínea em um hospital de referência no Brasil: usando MALDI-TOF/MS para identificar espécies incomuns de Candida
DOI:
https://doi.org/10.33448/rsd-v11i11.33243Palavras-chave:
Candidemia; MALDI-TOF/MS; Antifúngicos; Mortalidade.Resumo
A candidemia é um problema de saúde com alta taxa de mortalidade. Os objetivos deste estudo foram comparar a identificação de Candida spp. por meio de metodologias tradicionais e espectrometria de massa (MALDI-TOF/MS), verificar o perfil de suscetibilidade antifúngica desses isolados e analisar a evolução clínica dos pacientes. Esta foi uma coorte prospectiva de dois anos conduzida no Hospital de Clínicas de Uberlândia (HCU-UFU). Os isolados de Candida spp. foram identificados por meio de VITEK®-2 e MALDI-TOF/MS. Os testes de suscetibilidade antifúngica foram realizados via VITEK®-2. Os dados clínico-demográficos foram avaliados a partir de prontuários e as variáveis foram descritas como média, desvio padrão, frequência e porcentagem; os fatores de risco foram avaliados por meio de análise univariada e multivariada. Um total de 113 pacientes e 126 isolados de Candida spp. foram estudados. C. albicans foi a mais frequente (30%); MALDI-TOF/MS identificou espécies incomuns, incluindo identificação errônea de C. famata. A maioria dos isolados (95%) foi suscetível aos antifúngicos testados. A maioria dos pacientes era do sexo masculino (65%) e com idade superior a 60 anos (45%); 85% dos pacientes foram tratados com fluconazol. A taxa de mortalidade em 30 dias foi de 56%; os pacientes que não receberam tratamento e os que iniciaram mais tarde apresentaram menor sobrevida (p<0,0001). MALDI-TOF/MS foi capaz de identificar espécies incomuns de Candida spp. A doença apresentou alta mortalidade; a correta identificação das espécies envolvidas e a introdução de terapia adequada e oportuna são essenciais para aumentar a sobrevida do paciente.
Referências
Al-Dorzi, H. M., Sakkijha, H., Khan, R., Aldabbagh, T., Toledo, A., Ntinika, P., Al Johani, S. M., & Arabi, Y. M. (2020). Invasive Candidiasis in Critically Ill Patients: A Prospective Cohort Study in Two Tertiary Care Centers. Journal of intensive care medicine, 35(6), 542–553. https://doi.org/10.1177/0885066618767835
Almeida, F., Rodrigues, M. L., & Coelho, C. (2019). The Still Underestimated Problem of Fungal Diseases Worldwide. Frontiers in microbiology, 10, 214. https://doi.org/10.3389/fmicb.2019.00214
Alves, P., Melo, S., Bessa, M., Brito, M. O., Menezes, R. P., Araújo, L. B., Penatti, M., Pedroso, R., & Röder, D. (2020). Risk factors associated with mortality among patients who had candidemia in a university hospital. Revista da Sociedade Brasileira de Medicina Tropical, 53, e20190206. https://doi.org/10.1590/0037-8682-0206-2019
Ambaraghassi, G., Dufresne, P. J., Dufresne, S. F., Vallières, É., Muñoz, J. F., Cuomo, C. A., Berkow, E. L., Lockhart, S. R., & Luong, M. L. (2019). Identification of Candida auris by Use of the Updated Vitek 2 Yeast Identification System, Version 8.01: a Multilaboratory Evaluation Study. Journal of clinical microbiology, 57(11), e00884-19. https://doi.org/10.1128/JCM.00884-19
Arroyo-Mendoza, M., Peraza, K., Olson, J., Adler-Moore, J. P., & Buckley, N. E. (2020). Effect of testosterone and estrogen supplementation on the resistance to systemic Candida albicans infection in mice. Heliyon, 6(7), e04437. https://doi.org/10.1016/j.heliyon.2020.e04437
Bassetti, M., Giacobbe, D. R., Vena, A., Trucchi, C., Ansaldi, F., Antonelli, M., Adamkova, V., Alicino, C., Almyroudi, M. P., Atchade, E., Azzini, A. M., Carannante, N., Carnelutti, A., Corcione, S., Cortegiani, A., Dimopoulos, G., Dubler, S., García-Garmendia, J. L., Girardis, M., Cornely, O. A., … Montravers, P. (2019). Incidence and outcome of invasive candidiasis in intensive care units (ICUs) in Europe: results of the EUCANDICU project. Critical care (London, England), 23(1), 219. https://doi.org/10.1186/s13054-019-2497-3
Bienvenu, A. L., Pradat, P., Guerin, C., Aubrun, F., Fellahi, J. L., Friggeri, A., Guichon, C., Hernu, R., Menotti, J., Monard, C., Paulus, S., Rimmele, T., Piriou, V., Chidiac, C., Argaud, L., & Leboucher, G. (2020). Evaluation of first-line therapies for the treatment of candidemia in ICU patients: A propensity score analysis. International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases, 93, 15–21. https://doi.org/10.1016/j.ijid.2020.01.037
Cassagne, C., Normand, A. C., L'Ollivier, C., Ranque, S., & Piarroux, R. (2016). Performance of MALDI-TOF MS platforms for fungal identification. Mycoses, 59(11), 678–690. https://doi.org/10.1111/myc.12506
Castanheira, M., Woosley, L. N., Diekema, D. J., Jones, R. N., & Pfaller, M. A. (2013). Candida guilliermondii and other species of candida misidentified as Candida famata: assessment by vitek 2, DNA sequencing analysis, and matrix-assisted laser desorption ionization-time of flight mass spectrometry in two global antifungal surveillance programs. Journal of clinical microbiology, 51(1), 117–124. https://doi.org/10.1128/JCM.01686-12
Choi, H., Kim, J. H., Seong, H., Lee, W., Jeong, W., Ahn, J. Y., Jeong, S. J., Ku, N. S., Yeom, J. S., Kim, Y. K., Kim, H. Y., Song, Y. G., Kim, J. M., & Choi, J. Y. (2019). Changes in the utilization patterns of antifungal agents, medical cost and clinical outcomes of candidemia from the health-care benefit expansion to include newer antifungal agents. International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases, 83, 49–55. https://doi.org/10.1016/j.ijid.2019.03.039
Clinical and Laboratory Standards Institute (CLSI) (2017). Performance Standards for Antifungal Susceptibility Testing of Yeasts. 1st edition. CLSI supplement M60.
Colombo, A. L., Guimarães, T., Camargo, L. F., Richtmann, R., Queiroz-Telles, F. d., Salles, M. J., Cunha, C. A., Yasuda, M. A., Moretti, M. L., & Nucci, M. (2013). Brazilian guidelines for the management of candidiasis - a joint meeting report of three medical societies: Sociedade Brasileira de Infectologia, Sociedade Paulista de Infectologia and Sociedade Brasileira de Medicina Tropical. The Brazilian journal of infectious diseases: an official publication of the Brazilian Society of Infectious Diseases, 17(3), 283–312. https://doi.org/10.1016/j.bjid.2013.02.001
da Matta, D. A., Souza, A., & Colombo, A. L. (2017). Revisiting Species Distribution and Antifungal Susceptibility of Candida Bloodstream Isolates from Latin American Medical Centers. Journal of fungi (Basel, Switzerland), 3(2), 24. https://doi.org/10.3390/jof3020024
De Carolis, E., Hensgens, L. A., Vella, A., Posteraro, B., Sanguinetti, M., Senesi, S., & Tavanti, A. (2014). Identification and typing of the Candida parapsilosis complex: MALDI-TOF MS vs. AFLP. Medical mycology, 52(2), 123–130. https://doi.org/10.1093/mmy/myt009
Delavy, M., Dos Santos, A. R., Heiman, C. M., & Coste, A. T. (2019). Investigating Antifungal Susceptibility in Candida Species With MALDI-TOF MS-Based Assays. Frontiers in cellular and infection microbiology, 9, 19. https://doi.org/10.3389/fcimb.2019.00019
Doi, A. M., Pignatari, A. C., Edmond, M. B., Marra, A. R., Camargo, L. F., Siqueira, R. A., da Mota, V. P., & Colombo, A. L. (2016). Epidemiology and Microbiologic Characterization of Nosocomial Candidemia from a Brazilian National Surveillance Program. PloS one, 11(1), e0146909. https://doi.org/10.1371/journal.pone.0146909
Fontecha, G., Montes, K., Ortiz, B., Galindo, C., & Braham, S. (2019). Identification of Cryptic Species of Four Candida Complexes in a Culture Collection. Journal of fungi (Basel, Switzerland), 5(4), 117. https://doi.org/10.3390/jof5040117
Ghaith, D., Zafer, M. M., Hosny, T., & AbdElfattah, M. (2021). MALDI-TOF MS Overcomes Misidentification of the Uncommon Human Pathogen Candida famata by Routine Phenotypic Identification Methods. Current microbiology, 78(4), 1636–1642. https://doi.org/10.1007/s00284-021-02411-1
Gómez-Gaviria, M., & Mora-Montes, H. M. (2020). Current Aspects in the Biology, Pathogeny, and Treatment of Candida krusei, a Neglected Fungal Pathogen. Infection and drug resistance, 13, 1673–1689. https://doi.org/10.2147/IDR.S247944
Hart, E., Nguyen, M., Allen, M., Clark, C. M., & Jacobs, D. M. (2019). A systematic review of the impact of antifungal stewardship interventions in the United States. Annals of clinical microbiology and antimicrobials, 18(1), 24. https://doi.org/10.1186/s12941-019-0323-z
Hirayama, T., Miyazaki, T., Ito, Y., Wakayama, M., Shibuya, K., Yamashita, K., Takazono, T., Saijo, T., Shimamura, S., Yamamoto, K., Imamura, Y., Izumikawa, K., Yanagihara, K., Kohno, S., & Mukae, H. (2020). Virulence assessment of six major pathogenic Candida species in the mouse model of invasive candidiasis caused by fungal translocation. Scientific reports, 10(1), 3814. https://doi.org/10.1038/s41598-020-60792-y
Hosmer D. W., & Lemeshow S. (2004). Applied Logistic Regression. New York: John Wiley & Sons.
Huang, Y. S., Wang, F. D., Chen, Y. C., Huang, Y. T., Hsieh, M. H., Hii, I. M., Lee, Y. L., Ho, M. W., Liu, C. E., Chen, Y. H., & Liu, W. L. (2021). High rates of misidentification of uncommon Candida species causing bloodstream infections using conventional phenotypic methods. Journal of the Formosan Medical Association = Taiwan yi zhi, 120(5), 1179–1187. https://doi.org/10.1016/j.jfma.2020.11.002
Kadosh, D., & Mundodi, V. (2020). A Re-Evaluation of the Relationship between Morphology and Pathogenicity in Candida Species. Journal of fungi (Basel, Switzerland), 6(1), 13. https://doi.org/10.3390/jof6010013
Karapetsa, M., Tsolaki, V., Arabatzis, M., Petinaki, E., Velegraki, A., & Zakynthinos, E. (2019). Septic shock due to Candida famata (Debaryomyces hansenii) candidemia in an ICU immunocompetent trauma-patient. Journal of infection and public health, 12(4), 594–597. https://doi.org/10.1016/j.jiph.2018.12.015
Kim, S. H., Shin, J. H., Mok, J. H., Kim, S. Y., Song, S. A., Kim, H. R., Kook, J. K., Chang, Y. H., Bae, I. K., & Lee, K. (2014). Misidentification of Candida guilliermondii as C. famata among strains isolated from blood cultures by the VITEK 2 system. BioMed research international, 2014, 250408. https://doi.org/10.1155/2014/250408
Khouri S., Ruiz L.S., Aule M.E., Silva Bosco C.M., Pereira V.B.R., Domaneschi C., et al (2016). Evaluation of infections by Candida at a university hospital of Vale do Paraíba region, São Paulo State, Brazil: species distribution, colonization, risk factors and antifungal susceptibility. Rev Pan-Amaz Saude, 2016, 7:51-57. http://doi.org/10.5123/S2176-62232016000200006
Kronen, R., Hsueh, K., Lin, C., Powderly, W. G., & Spec, A. (2018). Creation and Assessment of a Clinical Predictive Calculator and Mortality Associated With Candida krusei Bloodstream Infections. Open forum infectious diseases, 5(2), ofx253. https://doi.org/10.1093/ofid/ofx253
Landis, J. R., & Koch, G. G. (1977). The measurement of observer agreement for categorical data. Biometrics, 33(1), 159–174.
Marins, T. A., Marra, A. R., Edmond, M. B., Martino, M., Yokota, P., Mafra, A., & Durão Junior, M. S. (2018). Evaluation of Candida bloodstream infection and antifungal utilization in a tertiary care hospital. BMC infectious diseases, 18(1), 187. https://doi.org/10.1186/s12879-018-3094-9
Medeiros, M., Melo, A., Bento, A. O., Souza, L., Neto, F., Garcia, J. B., Zuza-Alves, D. L., Francisco, E. C., Melo, A., & Chaves, G. M. (2019). Epidemiology and prognostic factors of nosocomial candidemia in Northeast Brazil: A six-year retrospective study. PloS one, 14(8), e0221033. https://doi.org/10.1371/journal.pone.0221033
Menezes, R., Ferreira, J. C., de Sá, W. M., Moreira, T., Malvino, L. D., de Araujo, L. B., Röder, D. V., Penatti, M. P., Candido, R. C., & Pedroso, R. (2015). FREQUENCY OF Candida SPECIES IN A TERTIARY CARE HOSPITAL IN TRIANGULO MINEIRO, MINAS GERAIS STATE, BRAZIL. Revista do Instituto de Medicina Tropical de Sao Paulo, 57(3), 185–191. https://doi.org/10.1590/S0036-46652015000300001
Pappas, P. G., Lionakis, M. S., Arendrup, M. C., Ostrosky-Zeichner, L., & Kullberg, B. J. (2018). Invasive candidiasis. Nature reviews. Disease primers, 4, 18026. https://doi.org/10.1038/nrdp.2018.26
Pfaller, M. A., Diekema, D. J., Procop, G. W., & Rinaldi, M. G. (2013). Comparison of the Vitek 2 yeast susceptibility system with CLSI microdilution for antifungal susceptibility testing of fluconazole and voriconazole against Candida spp., using new clinical breakpoints and epidemiological cutoff values. Diagnostic microbiology and infectious disease, 77(1), 37–40. https://doi.org/10.1016/j.diagmicrobio.2013.05.019
Pfaller, M. A., Diekema, D. J., Turnidge, J. D., Castanheira, M., & Jones, R. N. (2019). Twenty Years of the SENTRY Antifungal Surveillance Program: Results for Candida Species From 1997-2016. Open forum infectious diseases, 6(Suppl 1), S79–S94. https://doi.org/10.1093/ofid/ofy358
Pote, S. T., Sonawane, M. S., Rahi, P., Shah, S. R., Shouche, Y. S., Patole, M. S., Thakar, M. R., & Sharma, R. (2020). Distribution of Pathogenic Yeasts in Different Clinical Samples: Their Identification, Antifungal Susceptibility Pattern, and Cell Invasion Assays. Infection and drug resistance, 13, 1133–1145. https://doi.org/10.2147/IDR.S238002
Poissy, J., Damonti, L., Bignon, A., Khanna, N., Von Kietzell, M., Boggian, K., Neofytos, D., Vuotto, F., Coiteux, V., Artru, F., Zimmerli, S., Pagani, J. L., Calandra, T., Sendid, B., Poulain, D., van Delden, C., Lamoth, F., Marchetti, O., Bochud, P. Y., FUNGINOS, … Allfun French Study Groups (2020). Risk factors for candidemia: a prospective matched case-control study. Critical care (London, England), 24(1), 109. https://doi.org/10.1186/s13054-020-2766-1
Roilides, E., Carlesse, F., Leister-Tebbe, H., Conte, U., Yan, J. L., Liu, P., Tawadrous, M., Aram, J. A., Queiroz-Telles, F., & Anidulafungin A8851008 Pediatric Study Group (2019). A Prospective, Open-label Study to Assess the Safety, Tolerability and Efficacy of Anidulafungin in the Treatment of Invasive Candidiasis in Children 2 to <18 Years of Age. The Pediatric infectious disease journal, 38(3), 275–279. https://doi.org/10.1097/INF.0000000000002237
Roilides, E., Carlesse, F., Tawadrous, M., Leister-Tebbe, H., Conte, U., Raber, S., Swanson, R., Yan, J. L., Aram, J. A., Queiroz-Telles, F., & Anidulafungin A8851008 Pediatric Study Group (2020). Safety, Efficacy and Pharmacokinetics of Anidulafungin in Patients 1 Month to <2 Years of Age With Invasive Candidiasis, Including Candidemia. The Pediatric infectious disease journal, 39(4), 305–309. https://doi.org/10.1097/INF.0000000000002568
Rosner, B. (1995). Fundamentals of biostatistics. Belmont: Duxbury Press.
Tashiro, S., Osa, S., Igarashi, Y., Watabe, Y., Liu, X., Enoki, Y., Taguchi, K., Mayumi, T., Miyazaki, Y., Takesue, Y., & Matsumoto, K. (2020). Echinocandins versus non-echinocandins for the treatment of invasive candidiasis: A meta-analysis of randomized controlled trials. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 26(11), 1164–1176. https://doi.org/10.1016/j.jiac.2020.06.008
Toda, M., Williams, S. R., Berkow, E. L., Farley, M. M., Harrison, L. H., Bonner, L., Marceaux, K. M., Hollick, R., Zhang, A. Y., Schaffner, W., Lockhart, S. R., Jackson, B. R., & Vallabhaneni, S. (2019). Population-Based Active Surveillance for Culture-Confirmed Candidemia - Four Sites, United States, 2012-2016. Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002), 68(8), 1–15. https://doi.org/10.15585/mmwr.ss6808a1
Toubas, D., & Depaquit, J. (2012). Candida famata est-elle une espèce pathogène ? [Is Candida famata a pathogen?]. Annales de biologie clinique, 70(5), 623–624. https://doi.org/10.1684/abc.2012.0736
Tsai, M. H., Hsu, J. F., Yang, L. Y., Pan, Y. B., Lai, M. Y., Chu, S. M., Huang, H. R., Chiang, M. C., Fu, R. H., & Lu, J. J. (2018). Candidemia due to uncommon Candida species in children: new threat and impacts on outcomes. Scientific reports, 8(1), 15239. https://doi.org/10.1038/s41598-018-33662-x
Tsay, S. V., Mu, Y., Williams, S., Epson, E., Nadle, J., Bamberg, W. M., Barter, D. M., Johnston, H. L., Farley, M. M., Harb, S., Thomas, S., Bonner, L. A., Harrison, L. H., Hollick, R., Marceaux, K., Mody, R. K., Pattee, B., Shrum Davis, S., Phipps, E. C., Tesini, B. L., … Vallabhaneni, S. (2020). Burden of Candidemia in the United States, 2017. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 71(9), e449–e453. https://doi.org/10.1093/cid/ciaa193
Tumbarello, M., Posteraro, B., Trecarichi, E. M., Fiori, B., Rossi, M., Porta, R., de Gaetano Donati, K., La Sorda, M., Spanu, T., Fadda, G., Cauda, R., & Sanguinetti, M. (2007). Biofilm production by Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia. Journal of clinical microbiology, 45(6), 1843–1850. https://doi.org/10.1128/JCM.00131-07
Wan Ismail, W., Jasmi, N., Khan, T. M., Hong, Y. H., & Neoh, C. F. (2020). The Economic Burden of Candidemia and Invasive Candidiasis: A Systematic Review. Value in health regional issues, 21, 53–58. https://doi.org/10.1016/j.vhri.2019.07.002
Xie, T. A., Liu, Y. L., Liang, C., Huang, Y. Y., Li, J. W., Li, Z. W., Fan, S. J., Chen, J. T., Xia, Y., Li, X. Y., Ouyang, S., Ji, T. X., & Guo, X. G. (2019). Accuracy of matrix-assisted LASER desorption ionization-time of flight mass spectrometry for identification of Candida. Bioscience reports, 39(10), BSR20190859. https://doi.org/10.1042/BSR20190859
Zhai, B., Ola, M., Rolling, T., Tosini, N. L., Joshowitz, S., Littmann, E. R., Amoretti, L. A., Fontana, E., Wright, R. J., Miranda, E., Veelken, C. A., Morjaria, S. M., Peled, J. U., van den Brink, M., Babady, N. E., Butler, G., Taur, Y., & Hohl, T. M. (2020). High-resolution mycobiota analysis reveals dynamic intestinal translocation preceding invasive candidiasis. Nature medicine, 26(1), 59–64. https://doi.org/10.1038/s41591-019-0709-7
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