Skip to main content
Log in

Ten-Year Study of Species Distribution and Antifungal Susceptibilities of Candida Bloodstream Isolates at a Brazilian Tertiary Hospital

  • Published:
Mycopathologia Aims and scope Submit manuscript

Abstract

To describe the incidence and susceptibility profile of Candida bloodstream infections in a tertiary-care hospital, we performed a retrospective observational study from 1998 to 2007. Comorbidities and risk factors were compiled from all cases. In vitro susceptibility testing to fluconazole, itraconazole, voriconazole, and amphotericin B was performed for 100 isolates, and caspofungin was tested for C. parapsilosis complex. In a ten-year evaluation of candidemias, 44 % were caused by C. albicans, and species of the C. parapsilosis complex were the second most frequent agents (37 %). Other species presented lower incidences (C. tropicalis, 13 %, C. glabrata, 5 %, and C. krusei, 1 %). Neither C. dubliniensis nor C. metapsilosis were observed in this study. C. orthopsilosis (3 %) and C. parapsilosis stricto sensu (34 %) were also found. Species distribution was independent of catheterization, mechanical ventilation, or previous use of antifungals or corticoids. Parenteral nutrition administration was strongly related to C. glabrata infection, and the highest mortality (80 %) was observed in patients infected by this species. All C. albicans isolates showed high susceptibility to all tested drugs. However, two C. parapsilosis stricto sensu isolates presented high minimum inhibitory concentration (MIC) (4 mg/L each) to fluconazole, and one exhibited voriconazole MIC of 0.25 mg/L, highlighting the cross-resistance to these azoles. All isolates of C. tropicalis and C. glabrata showed no resistance to any drug tested. No difference was noted between C. parapsilosis and C. orthopsilosis susceptibilities to caspofungin. Our results suggest that resistance to amphotericin B, fluconazole, voriconazole, itraconazole, and caspofungin in Brazilian Candida bloodstream isolates is still uncommon.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Gudlaugsson O, Gillespie S, Lee K, et al. Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis. 2003;37:1172–7.

    Article  PubMed  Google Scholar 

  2. Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004;39:309–17.

    Article  PubMed  Google Scholar 

  3. Pfaller MA, Diekema DJ, Gibbs DL, et al. Geographic variation in the frequency of isolation and fluconazole and voriconazole susceptibilities of Candida glabrata: an assessment from the ARTEMIS DISK global antifungal surveillance program. Diagn Microbiol Infect Dis. 2010;67:162–71.

    Article  PubMed  CAS  Google Scholar 

  4. Colombo AL, Nucci M, Park BJ, et al. Epidemiology of candidemia in Brazil: a nationwide sentinel surveillance of candidemia in eleven medical centers for the Brazilian network candidemia study. J Clin Microbiol. 2006;44:2816–23.

    Article  PubMed  CAS  Google Scholar 

  5. Pereira GH, Muller PR, Szeszs MW, et al. Five-year evaluation of bloodstream yeast infections in a tertiary hospital: the predominance of non-C. albicans species. Med Mycol. 2010;48:839–42.

    Article  PubMed  CAS  Google Scholar 

  6. Sao Paulo. CVE Epidemiology Surveillance Center of the Secretary of Health of São Paulo State Government, Brazil. 2011. Disponible at: http://www.cve.sp.gov.br. Last access: 12/12/2011.

  7. Ruiz LS, Sugizaki MF, Montelli AC, et al. Fungemia by yeasts in Brazil: occurrence and phenotypic study of strains isolated at the Public Hospital. J Mycol Méd. 2005;15:13–21.

    Article  Google Scholar 

  8. Rodero L, Davel G, Córdoba S, et al. Estudio multicéntrico sobre candidiasis nosocomial en la República Argentina. Groupo EMIFN/multicenter study on nosocomial candidiasis in the Republic of Argentina. Rev Argent Microbiol. 1999;31:114–9.

    PubMed  CAS  Google Scholar 

  9. Godoy P, Tiraboschi IN, Severo LC, et al. Species distribution and antifungal susceptibility profile of CANDIDA spp. bloodstream isolates from Latin American Hospitals. Mem Inst Oswaldo Cruz. 2003;98(3):401–5.

    Article  PubMed  CAS  Google Scholar 

  10. França JCB, Ribeiro CEL, Queiroz-Telles F. Candidemia in a Brazilian tertiary care hospital: incidence, frequency of different species, risk factors and antifungal susceptibility. Rev Soc Bras Med Trop. 2008;41:23–8.

    Article  PubMed  Google Scholar 

  11. Odds FC, Hanson MF, Davidson AD, et al. One year prospective survey of Candida bloodstream infections in Scotland. J Med Microbiol. 2007;56:1066–75.

    Article  PubMed  CAS  Google Scholar 

  12. Leroy O, Gangneux JP, Montravers P, et al. Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005–2006). Crit Care Med. 2009;37:1612–8.

    Article  PubMed  Google Scholar 

  13. Shin JH, Shin DH, Song JW, et al. Electrophoretic Karyotype analysis of sequential Candida parapsilosis isolates from patients with persistent or recurrent fungemia. J Clin Microbiol. 2001;39:1258–63.

    Article  PubMed  CAS  Google Scholar 

  14. Morgan J. Global trends in candidemia: review of reports from 1995–2005. Curr Infect Dis Rep. 2005;7:429–39.

    Article  PubMed  Google Scholar 

  15. Dl Horn, Neofytos D, Anaissie EJ, et al. Epidemiology and outcomes of candidemia in, patients: data from the prospective antifungal therapy alliance registry. Clin Infect Dis. 2019;2009(48):1695–703.

    Google Scholar 

  16. Espinel-Ingroff A. Novel antifungal agents, targets or therapeutic strategies for the treatment of invasive fungal diseases: a review of the literature (2005–2009). Rev Iberoam Micol. 2009;26:15–22.

    Article  PubMed  Google Scholar 

  17. Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the infectious diseases society of America. Clin Infect Dis. 2009;48:503–35.

    Article  PubMed  CAS  Google Scholar 

  18. Chang MR, Correia FP, Costa LC, et al. Candida bloodstream infection: data from a teaching hospital in Mato Grosso do Sul. Brazil Rev Inst Med Trop S Paulo. 2008;50:265–8.

    Article  Google Scholar 

  19. Mannarelli BM, Kurtzman CP. A rapid identification of Candida albicans and other human pathogenic yeasts by using short oligonucleotides in a PCR. J Clin Microboil. 1998;36:1634–41.

    CAS  Google Scholar 

  20. Tavanti A, Davidson AD, Gow NAR, et al. Candida orthopsilosis and Candida metapsilosis spp. nov to replace Candida parapsilosis groups II and III. J Clin Microbiol. 2005;43:284–92.

    Article  PubMed  CAS  Google Scholar 

  21. Cuenca-Estrella M, Arendrup MC, Chryssanthou E, et al. Multicentre determination of quality control strains and quality control ranges for antifungal susceptibility testing of yeasts and filamentous fungi using the methods of the antifungal susceptibility testing subcommittee of the European committee on antimicrobial susceptibility testing (AFST-EUCAST). Clin Microbiol Infect. 2007;13:1018–22.

    Article  PubMed  CAS  Google Scholar 

  22. Rodríguez-Tudela JL, Arendrup MC, Cuenca-Estrella M, et al. Eucast breakpoints for antifungals. Drug News Perspect. 2010;23:93–7.

    Article  PubMed  Google Scholar 

  23. Clinical and Laboratory Standards Institute (CLSI). Reference method for broth dilution antifungal susceptibility testing of yeasts: third edition (M27–A3). Wayne, PA: CLSI; 2008.

    Google Scholar 

  24. Clinical and Laboratory Standards Institute (CLSI). Reference method for broth dilution antifungal susceptibility testing of yeasts: informational supplement (M27–S3). Wayne, PA: CLSI; 2008.

    Google Scholar 

  25. Pfaller MA, Diekema DJ, Andes D, et al. Clinical breakpoints for the Echinocandins and Candida revisited: integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria. Drug Resist Updat. 2011;14:164–76.

    Article  PubMed  CAS  Google Scholar 

  26. Nolte FS, Parkinson T, Falconer DJ. Isolation and characterization of flucanazole and amphotericin B-resistant Candida albicans from blood of two patients with leukemia. Antimicrob Agents Chemother. 1997;41:196–9.

    PubMed  CAS  Google Scholar 

  27. Meis JF, Ruhnke M, De Pauw BE, et al. Candida dubliniensis candidemia in patients with chemotherapy-induced neutropenia and bone marrow transplantation. Emerg Infect Dis. 1999;5:150–3.

    Article  PubMed  CAS  Google Scholar 

  28. Tortorano AM, Peman J, Bernhardt H, et al. Epidemiology of candidaemia in Europe: results of 28-month European confederation of medical mycology (ECMM) hospital-based surveillance study. Eur J Clin Microbiol Infect Dis. 2004;23:317–22.

    Article  PubMed  CAS  Google Scholar 

  29. Kibbler CC, Seaton S, Barnes RA, et al. Management and outcome of bloodstream infections due to Candida species in England and Wales. J Hosp Infect. 2003;54:18–24.

    Article  PubMed  CAS  Google Scholar 

  30. Messer SA, Moet GJ, Kirby JT, et al. Activity of contemporary antifungal agents, including the novel echinocandin anidulafungin, tested against Candida spp., Cryptococcus spp., and Aspergillus spp.: report from the SENTRY Antimicrobial Surveillance Program, (2006 to 2007). J Clin Microbiol. 2006;2009(47):1942–6.

    Google Scholar 

  31. Goldani LZ, Mario PSS. Candida tropicalis in a tertiary care hospital. J Infect. 2003;46:155–60.

    Article  PubMed  CAS  Google Scholar 

  32. Matta Da, Machado AM, Azevedo AC, et al. Antifungal susceptibility of 1000 Candida bloodstream isolates to 5 antifungal drugs: results of a multicenter study conducted in Sao Paulo, Brazil, 1995–2003. Diagnostic Microbiol Infect Dis. 2007;57:399–404.

    Article  Google Scholar 

  33. Tavanti A, Hensgens LA, Ghelardiet E, et al. Genotyping of Candida orthopsilosis clinical isolates by amplification fragment length polymorphism reveals genetic diversity among independent isolates and strain maintenance within patients. J Clin Microbiol. 2007;45:1455–62.

    Article  PubMed  CAS  Google Scholar 

  34. Tay ST, Na SL, Chong J. Molecular differentiation and antifungal susceptibilities of Candida parapsilosis isolated from patients with bloodstream infections. J Med Microbiol. 2009;58:185–91.

    Article  PubMed  CAS  Google Scholar 

  35. Lin D, Wu LC, Rinaldi MG, et al. Three distinct genotypes within Candida parapsilosis from clinical sources. J Clin Microbiol. 1995;33:1815–21.

    PubMed  CAS  Google Scholar 

  36. Zancopé-Oliveira RM, James MJ, Derossi AP, et al. Strain characterization of Candida parapsilosis fungemia by molecular typing methods. Eur J Clin Microbiol Infect Dis. 2000;19:514–20.

    Article  PubMed  Google Scholar 

  37. Silva AP, Miranda IM, Lisboa C, et al. Pevalence, distribution, and antifungal susceptibility profiles of Candida parapsilosis, C. orthopsilosis, and C. metapsilosis in a tertiary care hospital. J Clin Microbiol. 2009;47:2392–7.

    Article  PubMed  CAS  Google Scholar 

  38. Kocsube′ SM, To′Th C, Va′Gvo¨Lgyi I, et al. Occurrence and genetic variability of Candida parapsilosis sensu lato in Hungary. J Med Microbiol. 2007;56:190–5.

  39. Lockhart SR, Messer SA, Pfaller MA, et al. Geographic distribution and antifungal susceptibility of the newly described species Candida orthopsilosis and Candida metapsilosis, in comparison to the closely-related species Candida parapsilosis. J Clin Microbiol. 2008;46:2659–64.

    Article  PubMed  CAS  Google Scholar 

  40. Asadzadeh M, Ahmad S, Al-Sweih N, et al. Rapid molecular differentiation and genotypic heterogeneity among Candida parapsilosis and Candida orthopsilosis strains isolated from clinical specimens in Kuwait. J Med Microbiol. 2009;58:745–52.

    Article  PubMed  CAS  Google Scholar 

  41. Aquino VR, Lunardi LW, Goldani LZ, et al. Prevalence, susceptibility profile for fluconazole and risk factors for candidemia in a tertiary care hospital in southern Brazil. Braz J Infect Dis. 2005;9:411–8.

    Article  PubMed  Google Scholar 

  42. Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007;20:133–63.

    Article  PubMed  CAS  Google Scholar 

  43. Swinne D, Nolard N, Vanr P, et al. Bloodstream yeast infections: a 15-month survey. Epidemiol Infect. 2009;137:1037–40.

    Article  PubMed  CAS  Google Scholar 

  44. Jung SI, Shin JH, Song JH, et al. Multicenter surveillance of species distribution and antifungal susceptibilities of Candida bloodstream isolates in South Korea. Med Mycol. 2010;48:669–74.

    Article  PubMed  CAS  Google Scholar 

  45. Rodríguez-Tudela JL, Almirante B, Rodríguez-Pardo D, et al. Correlation of the MIC and Dose/MIC ratio of fluconazole to the therapeutic response of patients with mucosal Candidiasis and Candidemia. Antimicrob Agents Chemother. 2007;51:3599–604.

    Article  PubMed  Google Scholar 

  46. Ostrosky-Zeichner L, Rex JH, Pappas PG, et al. Antifungal susceptibility survey of 2,000 bloodstream Candida isolates in the United States. Antimicrob Agents Chemother. 2003;47:3149–54.

    Article  PubMed  CAS  Google Scholar 

  47. Zepelin MB, Kunz L, Ru¨ Chel R, et al. Epidemiology and antifungal susceptibilities of Candida spp. to six antifungal agents: results from a surveillance study on fungaemia in Germany from July 2004 to August 2005. J Antimicrobial Chemother. 2007;60:424–8.

    Article  Google Scholar 

  48. Matsumoto FE, Dias AL, Melhem MSC, et al. Antifungal susceptibility of bloodstream yeasts isolated at a public children’s hospital in Brazil: comparison of the Etest and the AFST-EUCAST microdilution method. Can J Microbiol. 2007;53:1300–6.

    Article  PubMed  CAS  Google Scholar 

  49. Hajjeh RA, Sofair AN, Harrison LH, et al. Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J Clin Microbiol. 2004;42:1519–27.

    Article  PubMed  Google Scholar 

  50. Arthington-Skaggs BA, Lee-Yang W, Ciblak MA, Frade JP, et al. Comparison of visual and spectrophotometric methods of broth microdilution MIC end point determination and evaluation of a sterol quantitation method for in vitro susceptibility testing of fluconazole and itraconazole against trailing and non-trailing Candida isolates. Antimicrob Agents Chemother. 2002;46:2477–81.

    Article  PubMed  CAS  Google Scholar 

  51. Dimopoulos G, Velegraki A, Falagas ME. A 10-year survey of antifungal susceptibility of candidemia isolates from intensive care unit patients in Greece. Antimicrob Agents Chemother. 2009;53:1242–4.

    Article  PubMed  CAS  Google Scholar 

  52. Wingard JR. Importance of Candida species other than C. albicans as pathogens in oncology patients. Clin Infect Dis. 1995;20:115–25.

    Article  PubMed  CAS  Google Scholar 

  53. Pfaller MA, Andes D, Diekema DJ. CLSI subcommittee for antifungal susceptibility testing. Wild-type MIC distributions, epidemiological cutoff values and species-specific clinical breakpoints for fluconazole and Candida: time for harmonization of CLSI and EUCAST broth microdilution methods. Drug Resist Updat. 2010;13:180–95.

    Article  PubMed  CAS  Google Scholar 

  54. Cuenca-Estrella M, Rodríguez-Tudela JL. Present status of the detection of antifungal resistance: the perspective from both sides of the ocean. Clin Microbiol Infect. 2001;7:46–53.

    Article  PubMed  CAS  Google Scholar 

  55. Forrest G. Role of antifungal susceptiblility testing in patients management. Curr Opin Infect Dis. 2006;19:538–43.

    Article  PubMed  CAS  Google Scholar 

  56. Espinel-Ingroff A, Arthington-Skaggs B, Iqbal N, et al. Multicenter evaluation of a new disk agar diffusion method for susceptibility testing of filamentous fungi with voriconazole, posaconazole, itraconazole, amphotericin B, and caspofungin. J Clin Microbiol. 2007;45:1811–20.

    Article  PubMed  CAS  Google Scholar 

  57. Coyle EA. Invasive candidiasis and the utillity of the antifungal susceptibility testing in the ICU. J Pharm Practice. 2010;23:33–7.

    Article  Google Scholar 

  58. Lin MY, Carmeli Y, Zumsteg J, et al. Prior antimicrobial therapy and risk for hospital-acquired Candida glabrata and Candida krusei fungemia: a case 25 case-control study. Antimicrob Agents Chemother. 2005;49:4555–60.

    Article  PubMed  CAS  Google Scholar 

  59. Playford EG, Marriott D, Nguyen Q, et al. Candidemia in nonneutropenic critically ill patients: risk factors for non-albicans Candida spp. Crit Care Med. 2008;36:2034–9.

    Article  PubMed  Google Scholar 

  60. Shorr AF, Lazarus DR, Sherner JH, et al. Do clinical features allow for accurate prediction of fungal pathogenesis in bloodstream infections? Potential implications of the increasing prevalence of non-albicans candidemia. Crit Care Med. 2007;35:1077–83.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Andrés Avelino Baez for the excellent technical support, to Dulcilena de Matos in charge of the culture collection. S.U.P. was supported by a master grant from CAPES (Coordenação de Aperfeiçoamento de Pessoal do Ensino Superior, and L.X.B. are supported by a master grant from FAPESP (Fundação de Apoio à Pesquisa do Estado de São Paulo).

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. S. C. Melhem.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bonfietti, L.X., Szeszs, M.W., Chang, M.R. et al. Ten-Year Study of Species Distribution and Antifungal Susceptibilities of Candida Bloodstream Isolates at a Brazilian Tertiary Hospital. Mycopathologia 174, 389–396 (2012). https://doi.org/10.1007/s11046-012-9566-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11046-012-9566-3

Keywords

Navigation