Article information
Resumen
La candidiasis invasora representa el 75% de las infecciones por hongos en pacientes hospitalizados, con una mortalidad que alcanza cifras hasta del 78%. La frecuencia de estas infecciones varía de acuerdo con el servicio de hospitalización y los factores de riesgo de los pacientes. Paralelamente, se han venido observando cambios en la epidemiología de las especies de Candida, variaciones en su prevalencia y en la resistencia a los antimicóticos según su localización geográfica. Por todo lo anterior, es imperativo establecer un diagnóstico temprano que lleve a la identificación correcta de la especie implicada de manera que se instaure un pronto y adecuado tratamiento antimicótico. El diagnóstico de la candidiasis invasora continúa siendo un reto, en el cual combinar los diferentes métodos diagnósticos, los microbiológicos, los inmunológicos y los nuevos moleculares, aún en desarrollo y validación, es la mejor estrategia para lograr un dictamen oportuno. En esta revisión se describen los métodos disponibles, sus limitaciones y las perspectivas de los que están en etapa de desarrollo y validación. En la última década se cuenta con métodos de referencia para la medición de susceptibilidad in vitro a los antimicóticos, lo cual ha permitido conocer los perfiles de sensibilidad de las diferentes especies de Candida a escala mundial y local.
Palabras claves:
Candida
candidiasis
diagnóstico convencional
diagnóstico molecular
susceptibilidad antimicóticos
Abstract
Invasive candidiasis represents 75% of fungal infections in hospitalized patients, with reported mortalities up to 78%. The frequency of these infections varies according to the hospital services and the risk factors of the patients. In parallel, changes in the epidemiology of the Candida species have been observed, in particular variations in their prevalence and in their resistance to antifungals according to geographic location. For these reasons it is crucial to establish an early diagnosis that identifies the pathogen to the species level in order to allow an appropriate therapeutic decision. The diagnosis of invasive candidiasis continues to be a challenge, where combining the different available methods (microbiologic, immunologic and new molecular approaches) is the best strategy to achieve a prompt and accurate diagnosis. We review the currently available assays for conventional and molecular diagnosis, their limitations, and the perspectives for assays that are now in development and validation. In the last decade, well established reference methods have become available for testing antifungal susceptibility and this has allowed worldwide and regional sensitivity profiles to be established for the different Candida species.
Key words:
Candida
candidiasis
conventional diagnosis
molecular diagnosis
antifungal susceptibility
Full text is only aviable in PDF
Referencias
[1.]
P.G. Pappas.
Invasive candidiasis.
Infect Dis Clin North Am, 20 (2006), pp. 485-506
[2.]
J. Pelroth, B. Choi, B. Spellberg.
Nosocomial fungal infections: epidemiology, diagnosis and treatment.
Med Mycol, 45 (2007),
[3.]
M.H. Kollef, L.M. Napolitano, J.S. Salomkin, R.G. Wunderink, I.G. Bae, V.G. Fowler, et al.
Health care-associated infection (HAI): a critical appraisal of the emerging treat-proceeding of the HAI summit.
Clin Infect Dis, 47 (2008), pp. 55-99
[4.]
G. Quindós.
Nosocomial candidemias and invasive candidiasis.
Med Clin, 134 (2010), pp. 17-19
[5.]
D.L. Horn, D. Meofystos, E.J. Anaissie, J.A. Fishman, W.J. Steinbach, A.J. Olyaei, et al.
Clinical characteristics of 2,019 patients with candidemia: data from the PATH Alliance Registry.
Clin Infect Dis, 48 (2009), pp. 1695-1703
[6.]
D. Neofytos, D. Horn, E. Anaisse, W. Steinback, A. Olyaei, J. Fishman, et al.
Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipient: analysis of PATH Alliance Registry.
Clin Infect Dis, 48 (2009), pp. 265-273
[7.]
M.A. Pfaller, D.J. Diekema, D.L. Gibbs, V.A. Newell, J.F. Meis, I.M. Gould, et al.
1997-2005: An 8.5-year analysis of susceptibilities of Candida and Other Yeast Species to Fluconazole and Voriconazole by CLSI Standardized Disk Diffusion Testing.
J Clin Microbiol, 45 (2007), pp. 1735-1745
[8.]
O. Leroy, J.P. Gangneux, P. Montravers, J.P. Mira, F. Gouin, J.P. Sollet, 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, 37 (2009), pp. 1612-1618
[9.]
P.G. Pappas, J.H. Rex, J. Lee, R.J. Hamill, R.A. Larsen, W. Powderly, et al.
A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patient.
Clin Infect Dis, 37 (2003), pp. 634-643
[10.]
T.E. Zaoutis, J. Aragon, J. Chu, J.A. Berlin, T.J. Walsh, C. Feudtner.
The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in united state; a propensity analysis.
Clin Infect Dis, 41 (2005), pp. 1232-1239
[11.]
B. Almirante, D. Rodríguez, B.J. Park, M. Cuenca-Estrella, A. Planes, M. Almela, et al.
Epidemiology and predictors of mortality in case of Candida bloodstream infection: results from population-based surveillance, Barcelona Spain, from 2002 to 2003.
J Clin Microbiol, 43 (2005), pp. 1829-1835
[12.]
K.C. Hazen, S.A. Howell.
Candida, Cryptococcus and other yeast of medical importance.
Manual of clinical Microbiology, 9th, pp. 1762-1788
[13.]
E.M. Johnson.
Rare and emerging Candida species.
Current Fungal Infection Reports, 3 (2009), pp. 152-159
[14.]
S.R. Lockhart, D.J. Diekema, M.A. Pfaller.
The Epidemiology of Fungal Infections.
Clinical Mycology, 2nd, pp. 1-14
[15.]
M.C. Dignani, J.S. Solomkin, E.J. Anaissie.
Candida.
Clinical Mycology, 2nd, pp. 197-229
[16.]
M.A. Pfaller, D.J. Diekema.
Epidemiology of invasive mycoses in North America.
Crit Rev Microbiol, 36 (2010), pp. 1-53
[17.]
M. Nucci, F. Queiroz-Telles, A.M. Tobón, A. Restrepo, A.L. Colombo.
Epidemiology of opportunistic fungal infections in Latin America.
Clin Infect Dis, 51 (2010), pp. 561-570
[18.]
A. Tavanti, A.D. Davidson, N.A. Gow, M.C. Maiden, F.C. Odds.
Candida orthopsilosis and Candida metapsilosis spp. nov. to replace Candida parapsilosis groups II and III.
J Clin Microbiol, 43 (2005), pp. 284-292
[19.]
J.D. Sobel.
Candidiasis.
Diagnosis and treatment of human mycoses, pp. 137-161
[20.]
G. Ramage, S.P. Saville, P.T. Derek, J.L. Lopez-Ribot.
Candida Biofilm: an Update.
Eucaryotic Cell, 4 (2005), pp. 633-638
[21.]
A. Colombo, M. Nucci, B.J. Park, S.A. Nouer, B. Arthington-Skaggs, D.A. Damatta, et al.
Epidemiology of candidemia in Brazil: a nationwide sentinel surveillance of candidemia in eleven medical centers.
J Clin Microbiol, 44 (2006), pp. 2816-2823
[22.]
B.J. Arkinson, R.E. Lewis, D.P. Kontioyiannis.
Candida lusitaniae fungemia in cancer patients; risk factors for amphotericine B failure and outcome.
Med Mycol, 46 (2008), pp. 541-546
[23.]
Zuluaga A, de Bedout C, Agudelo CA, Hurtado H, Arango M, Restrepo A, Gonzalez A. Sensibilidad a fluconazol y voriconazol de especies de Candida aisladas de pacientes provenientes de unidades de cuidados intensivos en Medellín, Colombia (2001-2007). Rev Iberoam Micol, en prensa.
[24.]
J. Pontón.
Utilidad de los marcadores biológicos en el diagnóstico de la candidiasis invasora.
Rev Iberoam Micol, 26 (2009), pp. 8-14
[25.]
A.N. Ellepola, C.J. Morrison.
Laboratory diagnosis of invasive candidiasis.
J Microbiol, 43 (2005), pp. 65-84
[26.]
M.T. Montagna, G. Caggiano, E. Borghi, G. Morace.
The role of the laboratory in the diagnosis of invasive candidiasis.
Drugs, 69 (2009), pp. 59-63
[27.]
L.L. Horvath, B.J. George, C.K. Murray, L.S. Harrison, D.R. Hospenthal.
Direct comparison of the BACTEC 9240 and BacT/ALERT 3D automated blood culture systems for candida growth detection.
Clin Microbiol, 42 (2004), pp. 115-118
[28.]
L.C. McDonald, M.P. Weinstein, J. Fune, S. Mirrett, L.G. Reimer, L.B. Reller.
Controlled comparison of BacT/ALERT FAN aerobic medium and BATEC fungal blood culture medium for detection of fungemia.
J Clin Microbiol, 39 (2001), pp. 622-624
[29.]
S. Mirrett, L.B. Reller, C.A. Petti, C.W. Woods, B. Vazirani, R. Sivadas, et al.
Controlled clinical comparison of BacT/ALERT standard aerobic medium with BACTEC standard aerobic medium for culturing blood.
J Clin Microbiol, 41 (2003), pp. 2391-2394
[30.]
H. Yera, B. Sendid, N. Francois, D. Camus.
Contribution of serological test and blood culture to early diagnosis of systemic candidiasis.
Eur J Clin Microbiol Infect Dis, 2001 (2001), pp. 864-870
[31.]
J.M. Achkar, B. Fries.
Candida infections of genitouriunary tract.
Clin Microbiol Rev, 25 (2010), pp. 253-273
[32.]
P.E. Charles.
Multifocal Candida species colonization as a trigger for early antifungal therapy in critically ill patients: what about other risk factors for fungal infection?.
Crit Care Med, 34 (2006), pp. 913-914
[33.]
C. Agvald-Ohman, L. Klingspor, H. Hjelmqvist, C. Edlund.
Invasive candidiasis in long–term patients at a multidisciplinary intensive care unit: candida colonization index, risk factors, treatment and outcome.
Scand J Infect Dis, 40 (2008), pp. 145-153
[34.]
D.A. Wilson, M.J. Joyce, L.S. Hall, L.B. Reller, G.D. Roberts, G.S. Hall, et al.
Multicenter evaluation of Candida albicans peptide nucleic acid fluorescent in situ hybridization probe for characterization of yeast isolates from blood cultures.
J Clin Microbio, 43 (2005), pp. 2909-2912
[35.]
J. Pontón.
El diagnóstico microbiológico independiente del cultivo en la candidiasis invasora. Importancia de los marcadores fúngicos.
Rev Iberoam Micol, 23 (2006), pp. 20-25
[36.]
R.C. Matthews, J.P. Burnie, S. Tabaqchali.
Isolation of immunodominant antigens from sera of patients with systemic candidiasis and characterization of serological response to Candida albicans.
J Clin Microbiol, 25 (1987), pp. 230-237
[37.]
R. Matthews, J. Burnie.
Cloning of a DNA sequence encoding a major fragment of the 47 kilodalton stress protein homologue of Candida albicans.
FEMS Microbiol Lett, 51 (1989), pp. 25-30
[38.]
J. Burnie, R. Matthews.
The role of antibodies against hsp90 in the treatment of fungal infections.
Drug News Perspect, 16 (2003), pp. 205-210
[39.]
A.B. Mason, M.E. Brandt, H.R. Buckley.
Enolase activity associated with a C. albicans cytoplasmic antigen.
Yeast, 5Spec (1989), pp. S231-S239
[40.]
A. Pitarch, J. Abian, M. Carrascal, M. Sánchez, C. Nombela, C. Gil.
Proteomics-based identification of novel Candida albicans antigens for diagnosis of systemic candidiasis in patients with underlying hematological malignancies.
Proteomics, 4 (2004), pp. 3084-3106
[41.]
A. Pitarch, A. Jiménez, C. Nombela, C. Gil.
Decoding serological response to Candida cell wall immunome into novel diagnostic, prognostic, and therapeutic candidates for systemic candidiasis by proteomic and bioinformatic analyses.
Mol Cell Proteomics, 5 (2006), pp. 79-96
[42.]
C.J. Clancy, M.J. Clancy, M. Nguyen, S. Cheng, H. Huang, G. Fan, et al.
Immunoglobulin G responses to a Panel of Candida albicans antigens as accurate and early markers for the presence of systemic candidiasis.
J Clin Microbiol, 46 (2008), pp. 1647-1654
[43.]
F.R. Persat, M.A. Topenot, A. Piens, A. Thiebaut, E. Dannaoui, S. Picot.
Evaluation of different commercial ELISA methods for the serodiagnosis of systemic candidosis.
Mycoses, 45 (2002), pp. 455-546
[44.]
P.L. White, A.E. Archer, R.A. Barnes.
Comparison of non-culture methods for detection of systemic fungal infections, with emphasis on invasive Candida infections.
J. Clin Microbiol, 43 (2005), pp. 2181-2187
[45.]
P.L. White, R. Barton, M. Guiver, C.J. Linton, S. Wilson, M. Smith, et al.
A consensus on fungal polymerase chain reaction diagnosis?.: a United kingdom-ireland evaluation of polymerase chain reaction methods for detection of systemic fungal infections.
J Mol Diagn, 8 (2006), pp. 376-384
[46.]
B. De Pauw, T.J. Walsh, J.P. Donnelly, D.A. Stevens, J.E. Edwards, T. Calandra, et al.
Revised definitions of invasive fungal disease from the European Organization in Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycosis Study Group (EORTC/MSG) Consensus Group.
Clin Infec Dis, 46 (2008), pp. 1813-1821
[47.]
M. Guiver, L. Levi, B.A. Oppenheim.
Rapid identification of Candida species by TaqMan PCR.
J Clin Pathol, 54 (2001), pp. 362-366
[48.]
M.C. Hsu, K.W. Chen, H.J. Lo, Y.C. Chen, M.H. Liao, Y.H. Lin, et al.
Species identification of medically important fungi by use of realtime Light Cycler PCR.
J Med Microbiol, 52 (2003), pp. 1071-1076
[49.]
L. Metwally, D.J. Fairley, P.V. Coyle, R.J. Hay, S. Hedderwick, B. McCloskey, et al.
Improving molecular detection of Candida DNA in whole blood: comparison of seven fungal DNA extraction protocols using real-time PCR.
J Med Microbiol, 57 (2008), pp. 296-303
[50.]
L. Metwally, D.J. Fairley, P.V. Coyle, R.J. Hay, S. Hedderwick, B. McCloskey, et al.
Comparison of serum and whole blood specimens for the detection of Candida DNA in critically ill, non-neutropenic patients.
J Med Microbiol, 57 (2008), pp. 1269-1272
[51.]
R. McMullan, L. Metwally, P.V. Coyle, S. Hedderwick, B. McCloskey, H.J. O’Neill, et al.
A prospective clinical trial of a real-time polymerase chain reaction assay for the diagnosis of candidemia in nonneutropenic, critically ill adults.
Clin Infect Dis, 46 (2008), pp. 890-896
[52.]
J. Bennett.
Is real-time polymerase chain reaction ready for real use in detecting candidemia?.
Clin Infect Dis, 46 (2008), pp. 897-898
[53.]
L.S. Hall, S. Wohlfield, G.D. Roberts.
Experience with the MicroSeq D2 large-subunit ribosomal DNA sequencing kit for identification of commonly encountered, clinically important yeast species.
J Clin Microbiol, 41 (2003), pp. 5099-5102
[54.]
C. Muñoz-Cadavid, S. Rudd, S. Zaki, M. Patel, M. Moser, M.E. Brandt, et al.
Improving molecular detection of fungal DNA in FFPE tissues: comparison of five tissue DNA extraction methods using panfungal PCR.
J Clin Microbiol, 48 (2010), pp. 2147-2153
[55.]
Clinical Laboratory Standards Institute (CLSI).
Reference method for broth dilution antifungal susceptibility testing of yeast. Approved standard M27-A3.
National Committee for Clinical Laboratory Standards, (2008),
[56.]
Clinical Laboratory Standards Institute (CLSI).
Method for antifungal disk diffusion susceptibility testing of yeast. Approved guideline M44-A.
National Committee for Clinical Laboratory Standards, (2004),
[57.]
Clinical Laboratory Standards Institute (CLSI).
Reference method for broth dilution antifungal susceptibility testing of yeast.
Third informational supplement. M27-S3, National Committee for Clinical Laboratory Standards, (2008),
[58.]
M.A. Pfaller, D.J. Diekema, D.L. Gibbs, V.A. Newell, E. Nagy, S. Dobiasova, et al.
Candida krusei, a multidrug-resistant opportunistic fungal pathogen: Geographic and temporal trends from the ARTEMIS DISK antifungal surveillance program.
J Clin Microbiol, 46 (2008), pp. 515-521
[59.]
M.A. Pfaller, D.J. Diekema, D.L. Gibbs, V.A. Newell, K.P. Ng, A. Colombo, et al.
Geographic and Temporal Trends in Isolation and Antifungal Susceptibility of Candida parapsilosis: a Global Assessment from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005.
J Clin Microbiol, 43 (2008), pp. 842-849
Copyright © 2010. Asociación Colombiana de Infectología (ACIN)
