Characterization of Candida spp. isolated from the bloodstream in a reference hospital in Brazil: using MALDI-TOF/MS to identify unusual species of Candida

Authors

DOI:

https://doi.org/10.33448/rsd-v11i11.33243

Keywords:

Candidemia; MALDI-TOF/MS; Antifungal agents; Mortality.

Abstract

Candidemia is a health problem with a high mortality rate. The aims of this study were to compare the identification of Candida spp. via traditional methodologies and mass spectrometry (MALDI-TOF/MS) in order to verify the antifungal susceptibility profile of these isolates and analyze the clinical evolution of patients. This was a two-year prospective cohort conducted at the Hospital de Clínicas de Uberlândia (HCU-UFU). Candida spp. were identified via VITEK®-2 and MALDI-TOF/MS. Antifungal susceptibility tests were conducted via VITEK®-2. Clinical-demographic data were assessed from medical records and variables were described as mean, standard deviation, frequency and percentage, and risk factors were evaluated using univariate and multivariate analysis. A total of 113 patients and 126 Candida spp. isolates were studied. C. albicans was most frequent (30%); MALDI-TOF/MS identified unusual species, including misidentification of C. famata. Most of the isolates (95%) were susceptible to the tested antifungals. Most patients were men (65%) and older than 60 years of age (45%); 85% of patients were treated with fluconazole. The 30-day mortality rate was 56%; patients who did not receive treatment and those who started later had a lower survival rate (p <0.0001). MALDI-TOF/MS was able to identify unusual Candida spp. Candidemia presented a high mortality rate; the correct identification of Candida spp. and the introduction of appropriate and timely therapy are essential for increasing patient survival.   

References

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

Downloads

Published

15/08/2022

How to Cite

AGUIAR, P. A. D. F. de; MENEZES, R. de P.; PENATII, M. P. A.; ARAÚJO, L. B. de .; RÖDER, D. V. D. de B. Characterization of Candida spp. isolated from the bloodstream in a reference hospital in Brazil: using MALDI-TOF/MS to identify unusual species of Candida . Research, Society and Development, [S. l.], v. 11, n. 11, p. e69111133243, 2022. DOI: 10.33448/rsd-v11i11.33243. Disponível em: https://www.rsdjournal.org/index.php/rsd/article/view/33243. Acesso em: 19 apr. 2024.

Issue

Section

Health Sciences