Increase of Non-albicans Candida Species and Their Antifungal Susceptibility in Intensive Care Unit Patients (Mexico)

Rosa Paulina Calvillo-Medina1, Rocio Alejandrina Mejía-Romero2, Magda Martínez-Neria3, Juan José Olalde-Elias4, Fernando Domínguez-Márquez4
1Universidad Autónoma de Querétaro, Querétaro, Mexico
2Laboratorio de Microbiología, Hospital del Niño y la Mujer “Dr. Felipe Núñez Lara”, Querétaro, Mexico
3Hospital Central Sur de Alta Especialidad PEMEX, Ciudad de Mexico, Mexico
4Hospital General de Querétaro, Servicios de Salud del Estado de Querétaro, Querétaro, Mexico

Tóm tắt

In Mexico, little is known about candidemia by non-albicans Candida species, or the antifungal susceptibility of such strains without performing antifungal tests; fluconazole is one of the most used treatments in empirical therapy. In the present study, we included patients from the intensive care unit of one hospital in Mexico (2019–2020) with yeast infection and positive cultures. Yeasts obtained from cultivable isolates were identified using an automated identification instrument and by PCR (nrDNA ITS), and their susceptibilities to six antifungals were characterized across a range of concentrations. Yeast cultures from 105 patients which were suspected etiological agents of primary diagnosis were recovered and identified as mainly non-albicans Candida species (57.2%). The most prevalent was C. glabrata (41.9%), followed by C. albicans, C. krusei, C. parapsilosis, C. tropicalis, and Cryptococcus neoformans. The most common infection site was urine (56%), followed by the bronchial aspirate (30%). Most isolated fungi were susceptible to 5-flucytosine (98%) and amphotericin B. However, C. glabrata, C. krusei, and C. tropicalis demonstrated to be resistant to itraconazole, miconazole, and fluconazole. The present investigation contributes to the knowledge of non-albicans Candida species infections in patients and opens the possibility for a better understanding and management in antifungal empirical therapy in Mexico.

Từ khóa


Tài liệu tham khảo

González GM, Elizondo M, Ayala J. Trends in species distribution and susceptibility of bloodstream isolates of Candida collected in Monterrey, Mexico, to seven antifungal agents: results of a 3-year (2004 to 2007) surveillance study. J Clin Microbiol. 2008;46:2902–5. https://doi.org/10.1128/JCM.00937-08.

Reyes-Montes M, Duarte-Escalante E, Martínez-Herrera E, et al. Current status of the etiology of candidiasis in Mexico. Rev Iberoam Micol. 2017;34:203–10. https://doi.org/10.1016/j.riam.2017.05.001.

Gamage H, Sivanesan P, Hipler U-C, et al. Superficial fungal infections in the department of dermatology, University Hospital Jena: a 7-year retrospective study on 4556 samples from 2007 to 2013. Mycoses. 2020;63:558–65. https://doi.org/10.1111/myc.13077.

Kwizera R, Bongomin F, Lukande R. Deep fungal infections diagnosed by histology in Uganda: a 70-year retrospective study. Med Mycol. 2020;58:1044–52. https://doi.org/10.1093/mmy/myaa018.

Verduyn-Lunel FM, Meis JF, Voss A. Nosocomial fungal infections: candidemia. Diagn Microbiol Infect Dis. 1999;34:213–20. https://doi.org/10.1016/S0732-8893(99)00035-8.

Perlroth J, Choi B, Spellberg B. Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Med Mycol. 2007;45:321–46. https://doi.org/10.1080/13693780701218689.

Pemán J, Quindós G. Aspectos actuales de las enfermedades invasoras causadas por Candida y otros hongos levaduriformes. Rev Iberoam Micol. 2016;33:133–9. https://doi.org/10.1016/j.riam.2015.10.001.

Escribano P, Sánchez-Carrillo C, Muñoz P, Bouza E. Reduction in percentage of clusters of Candida albicans and Candida parapsilosis causing candidemia in a general hospital in Madrid España. J Clin Microbiol. 2018;56:1–9.

Mourad A, Perfect J. Present and future therapy of Cryptococcus infections. J Fungi. 2018;4:79. https://doi.org/10.3390/jof4030079.

Vitális E, Nagy F, Tóth Z, et al. Candida biofilm production is associated with higher mortality in patients with candidaemia. Mycoses. 2020;63:352–60. https://doi.org/10.1111/myc.13049.

Büyüktuna SA, Hasbek M, Elaldi N, et al. Epidemiological analysis of nosocomial Candida infections: Experience of a university hospital. Cumhuriyet Med J. 2019:318–27. https://doi.org/10.7197/223.vi.553114.

Medeiros MA, Melo AP, Bento AD, et al. Epidemiology and prognostic factors of nosocomial candidemia in northeast Brazil: a six-year retrospective study. PLoS One. 2019;14:e0221033.

Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis : 2016 Update by the infectious diseases society of America. Clin Infect Dis. 2016;62:1–50. https://doi.org/10.1093/cid/civ933.

Kothavade RJ, Kura MM, Valand AG, et al. Candida tropicalis: its prevalence, pathogenicity and increasing resistance to fluconazole. J Med Microbiol. 2010;59:873–80. https://doi.org/10.1099/jmm.0.013227-0.

Ruhnke M. Antifungal stewardship in invasive Candida infections. Clin Microbiol Infect. 2014;20:11–8. https://doi.org/10.1111/1469-0691.12622.

Hani U, Shivakumar H, Vaghela RM, et al. Candidiasis: fungal infection- current challenges and progress in prevention and treatment. Infect Disord Drug Targets. 2015;15:42–52. https://doi.org/10.2174/1871526515666150320162036.

Bailly S, Maubon D, Fournier P, et al. Impact of antifungal prescription on relative distribution and susceptibility of Candida spp. - Trends over 10 years. J Infect. 2016;72:103–11. https://doi.org/10.1016/j.jinf.2015.09.041.

Corzo-Leon DE, Alvarado-Matute T, Colombo AL, et al. Surveillance of Candida spp bloodstream infections: epidemiological trends and risk factors of death in two Mexican tertiary care hospitals. PLoS One. 2014;9:1–6. https://doi.org/10.1371/journal.pone.0097325.

Calvillo-Medina RP, Martínez-Neria M, Mena-Portales J, et al. Identification and biofilm development by a new fungal keratitis aetiologic agent. Mycoses. 2019;62(1):62–72. https://doi.org/10.1111/myc.12849.

White T, Bruns T, Lee S, et al. Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics. In: Innis MA, Gelfand DH, Sninsky SS, White TJ, editors. PCR Protocols: A Guide to Methods and Applications. New York: Academic Press Inc; 1990. p. 315–22.

Morales Y, Moncada D, Arroyo S, et al. Candidemias en un hospital general de la Ciudad de México: estudio de sensibilidad a antifúngicos con el método de microplaca colorimétrica y microdilución en caldo. Dermotol Rev Mex. 2013;57:155–8.

Bustamante B, Martins MA, Bonfietti LX, et al. Species distribution and antifungal susceptibility profile of Candida isolates from bloodstream infections in Lima, Peru. J Med Microbiol. 2014;63:855–60. https://doi.org/10.1099/jmm.0.071167-0.

CLSI. Reference method for broth dilution antifungal susceptibility testing of yeasts; 4th informational supplement M27– S4. Wayne: Clinical and Laboratory Standards Institute; 2012.

Sánchez-Vargas LOS, Ortiz-López NG, Villar M, et al. Point prevalence, microbiology and antifungal susceptibility patterns of oral Candida isolates colonizing or infecting Mexican HIV/AIDS patients and healthy persons. Rev Iberoam Micol. 2005;22:83–92. https://doi.org/10.1016/S1130-1406(05)70014-0.

Hernández-Solís SE, Rueda-Gordillo F, Pereira-Góngora JR, et al. Frecuencia de portadores de C. albicans en un grupo de niños de una comunidad rural del estado de Yucatán. Rev Odontol Latinoam. 2008;1:1–4.

Lao M, Li C, Li J, et al. Opportunistic invasive fungal disease in patients with type 2 diabetes mellitus from Southern China: clinical features and associated factors. J Diabetes Investig. 2020;11:731–44. https://doi.org/10.1111/jdi.13183.

de la Torre-Saldaña VA, Martínez-Velázquez M, Reséndiz-Sánchez J. Factores de riesgo y epidemiología de la candidemia en el Hospital Juárez de México. Med Int Mex. 2014;30:121–32.

Manzano-Gayosso P, Méndez-Tovar LJ, Arenas R, et al. Levaduras causantes de onicomicosis en cuatro centros dermatológicos mexicanos y su sensibilidad antifúngica a compuestos azólicos. Rev Iberoam Micol. 2011;28:32–5. https://doi.org/10.1016/j.riam.2010.11.002.

Lionakis MS, Lewis RE, Kontoyiannis DP. Breakthrough invasive mold infections in the hematology patient: current concepts and future directions. Clin Infect Dis. 2018;67:1621–30.

Jenks JD, Cornel OA, Chen SC-A, et al. Breakthrough invasive fungal Infections: who is at risk? Mycoses. 2020;63:1021–32. https://doi.org/10.1111/myc.13148.

Sanchez-Vargas LOS, Eraso E, Carrillo-Muñoz AJ, et al. In vitro activity of voriconazole against Mexican oral yeast isolates. Mycoses. 2010;53:200–3. https://doi.org/10.1111/j.1439-0507.2009.01702.x.

Queiroz-Telles F, Nucci M, Colombo AL, et al. Mycoses of implantation in Latin America: an overview of epidemiology, clinical manifestations, diagnosis and treatment. Med Mycol. 2011;49:225–36. https://doi.org/10.3109/13693786.2010.539631.

Pfaller MA, Diekema DJ. Progress in antifungal susceptibility testing of Candida spp. by use of clinical and laboratory standards institute broth microdilution methods, 2010 to 2012. J Clin Microbiol. 2012;50:2846–56.