Regístrese
Buscar en
Revista Iberoamericana de Micología
Toda la web
Inicio Revista Iberoamericana de Micología Candidaemia due to Candida parapsilosis species complex at a hospital in Brazil:...
Información de la revista
Vol. 34. Núm. 2.
Páginas 106-108 (Abril - Junio 2017)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 34. Núm. 2.
Páginas 106-108 (Abril - Junio 2017)
Note
DOI: 10.1016/j.riam.2016.06.008
Acceso a texto completo
Candidaemia due to Candida parapsilosis species complex at a hospital in Brazil: Clinical characteristics and antifungal susceptibility profile
Candidemia por especies del complejo Candida parapsilosis en un hospital de Brasil: características clínicas y perfil de sensibilidad a los antifúngicos
Visitas
740
Débora de Souza Olartechea de Alencara, Rosianne Assis de Sousa Tsujisakia, Fernanda Luiza Espinosa Sposittoa, Maína de Oliveira Nunesa, Adriana Araújo de Almeidaa, Marilena dos Anjos Martinsb, Marcia de Souza Carvalho Melhemb, Marilene Rodrigues Changa,
Autor para correspondencia
marirchang@yahoo.com.br

Corresponding author.
a Laboratório de Pesquisas Microbiológicas, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil
b Divisão de Micologia, Instituto Adolfo Lutz, São Paulo, SP, Brazil
Este artículo ha recibido
740
Visitas
Información del artículo
Resumen
Texto completo
Bibliografía
Descargar PDF
Estadísticas
Tablas (1)
Table 1. Characteristics of seven patients with haematogenous candidaemia caused by species of the Candida parapsilosis complex and respective antifungal susceptibility profiles.
Abstract
Background

Recent decades have seen a global emergence of candidaemia caused by non-Candida albicans Candida species, particularly the Candida parapsilosis complex.

Aims

To evaluate the clinical features and antifungal susceptibility profiles of isolates belonging to the C. parapsilosis species complex in patients with candidaemia in a midwestern Brazilian tertiary-care teaching hospital.

Methods

Yeast identification was performed using an automated Vitek 2 Compact system. PCR-RFLP was employed for species differentiation.

Results

Five cases of infection by C. parapsilosis sensu stricto and two by Candida orthopsilosis were found. Of the seven cases, five were adult patients undergoing haemodialysis. The only isolate of C. parapsilosis sensu stricto resistant to fluconazole (MIC=8μg/ml) was obtained from a patient on a long-term regimen with this drug. This was the only patient who evolved to death.

Conclusions

Resistance to antifungal agents poses a therapeutic challenge, especially for non-C. albicans Candida species, and requires continuous monitoring using susceptibility tests because resistance in vitro can be predictive of treatment failure. In the present study, in vitro antifungal susceptibility proved consistent with clinical outcome.

Keywords:
Candidaemia
Candida parapsilosis
Candida orthopsilosis
Antifungal agents
Resumen
Antecedentes

En las últimas décadas se ha visto un surgimiento mundial de la candidemia causada por especies de Candida no-C. albicans, en particular del complejo Candida parapsilosis.

Objetivos

Evaluar las características clínicas y los perfiles de sensibilidad antifúngica en aquellos aislamientos del complejo de especies C. parapsilosis responsables de candidemia en un hospital universitario de tercer nivel en la región centro-oeste de Brasil.

Métodos

La identificación se realizó en un sistema automatizado Vitek 2 compact. Se utilizó PCR-RFLP para la diferenciación de las especies.

Resultados

Se encontraron cinco casos de candidemia por C. parapsilosis sensu stricto y dos por Candida orthopsilosis. Cinco eran pacientes adultos sometidos a hemodiálisis. El único aislamiento de Candida parapsilosis sensu stricto resistente a fluconazol (CIM, 8μg/ml) se obtuvo de un paciente en régimen largo de tratamiento con este antifúngico. Este fue el único paciente que murió.

Conclusiones

La resistencia a los antifúngicos constituye un desafío terapéutico, en especial contra las especies de Candida no-C. albicans, que requieren la monitorización continua por medio de pruebas de sensibilidad en vista de que la resistencia in vitro puede ser predictiva de fracaso del tratamiento. En el presente estudio la sensibilidad antifúngica in vitro resultó consistente con el curso clínico.

Palabras clave:
Candidemia
Candida parapsilosis
Candida orthopsilosis
Agentes antifúngicos
Texto completo

Recent decades have seen a global emergence of candidaemia caused by non-Candida albicans Candida species, particularly of the Candida parapsilosis complex.2,6,15 Determination of antifungal susceptibility is important to ensure effective monitoring and detection of resistance, contributing to appropriate treatment selection.13

The purposes of this study were to evaluate the clinical features of patients with candidaemia caused by species of the C. parapsilosis complex and to determine the antifungal susceptibility profiles of these agents.

The yeasts were isolated from a tertiary-care teaching hospital located in Campo Grande, Mato Grosso do Sul State, Midwest Brazil, from March 2010 to March 2012. The isolates were detected in blood culture using an automated Bact/Alert system and identified employing an automated Vitek 2 Compact system (both from bioMérieux, France).

Species differentiation was performed by polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP). DNA extraction, conducted as described by Sambrook et al.,16 was carried out at the Mycology Laboratory of the Instituto Adolfo Lutz, in São Paulo City. PCR-RFLP was performed according to Tavanti et al.17 The results were interpreted by comparison against standard strains (C. parapsilosis ATCC 22019, Candida orthopsilosis ATCC 96139, and Candida metapsilosis ATCC 96144).

The minimum inhibitory concentrations of the antifungal agents amphotericin B (Sigma Aldrich, USA), fluconazole (Sigma Aldrich), itraconazole (Sigma Aldrich), and voriconazole (Pfizer, USA) were determined using a broth microdilution method according to the M27-A3 guidelines of the Clinical and Laboratory Standards Institute.3 Interpretation of the minimum inhibitory concentrations for amphotericin B and itraconazole was based on the M27-S3 document3; for fluconazole and voriconazole, the M27-S4 guidelines4 were followed.

Retrospective demographic and clinical data were obtained from medical records. The study was approved by the Universidade Federal de Mato Grosso do Sul Research Ethics Committee (permit 1591/2010).

In the two-year period investigated, 32 patients were laboratory-diagnosed with candidaemia, predominantly caused by non-C. albicans Candida species (65.6% of cases). The C. parapsilosis complex predominated (7/32; 21.9%), comprising five isolates of C. parapsilosis sensu stricto and two of C. orthopsilosis. Except for one C. parapsilosis isolate resistant to fluconazole, all yeasts were susceptible to the antifungals tested. Table 1 shows the principal clinical and laboratory features of the seven patients.

Table 1.

Characteristics of seven patients with haematogenous candidaemia caused by species of the Candida parapsilosis complex and respective antifungal susceptibility profiles.

Patient  Age (years)  Ward  Underlying condition  Treatment  FLZa (μg/ml)  ITZb
(μg/ml) 
VCZa
(μg/ml) 
AMBb
(μg/ml) 
Species
(PCR-RFLP) 
33  AICU  CRF, DM  FLZ  0.25  0.125  0.015  0.5  C. orthopsilosis 
PICU  –  FLZ+AMB  0.5  0.06  0.015  C. parapsilosis 
48  RCU  CRF, DM  FLZ  0.25  0.06  0.015  0.5  C. parapsilosis 
72  RCU  CRF, DM  –  0.25  0.06  0.015  0.5  C. parapsilosis 
<1  NNU  PB  FLZ  0.125  0.06  0.015  0.5  C. orthopsilosis 
69  RCU  CRF  FLZ  0.125  0.015  0.015  0.5  C. parapsilosis 
59  RCU  CRF, DM  FLZ  0.125  0.06  C. parapsilosis 

AICU: adult intensive care unit; PICU: pediatric intensive care unit; RCU: renal care unit; NNU: newborn nursery unit; CRF: chronic renal failure, DM: diabetes mellitus; PB: preterm birth; FLZ: fluconazole; ITZ: itraconazole; VCZ: voriconazole; AMB: amphotericin B.

a

M27-S4 (CLSI 2012), 24h reading.

b

M27-S3 (CLSI 2008), 48h reading.

C. parapsilosis sensu stricto and C. orthopsilosis jointly accounted for the majority of non-C. albicans Candida species isolated from the blood cultures – a finding that corroborates data collected from other Brazilian hospitals.5,10

In a tertiary-care hospital in Spain,8C. parapsilosis sensu stricto was the most frequent microorganism (90.3%) out of the 62 isolates pertaining to the C. parapsilosis complex isolated from blood, followed by C. orthopsilosis (9.7%).

Fever, tachycardia, and dyspnea were the most frequent clinical symptoms (3/7; 42.9%) at the time of candidaemia diagnosis. All patients had previously undergone procedures known for their associated high risk of nosocomial infection by Candida species – namely, haemodialysis or previous use of vancomycin (5 cases each); surgery within 30 days before the onset of candidaemia (3 cases); and use of nasogastric, orogastric, nasoenteral, or indwelling urinary catheter (2 cases each). These findings are similar to those of previous studies conducted in Brazil.1,2,12

All patients with candidaemia had used central venous catheters. In the two pediatric patients included in the present study, the yeasts were also isolated from the catheter tips, corroborating studies that underscore the risks of invasive fungal infection associated with these devices, given the ability of these microorganisms to form biofilms.8,14 All five adult subjects were chronic renal failure patients undergoing haemodialysis with double-lumen catheters. The research literature reports cases of infection by species of the C. parapsilosis complex in patients with this profile.5,9 In the present study, four of the five adults with chronic renal failure had diabetes mellitus, which also constitutes a risk factor for invasive fungal infection.

A 33-year-old patient with diabetes mellitus and chronic renal failure on haemodialysis developed endocarditis. C. orthopsilosis was isolated not only from blood cultures but also from a post-surgical fragment of cardiac valve – a documented case of infective endocarditis caused by this microorganism, albeit rarely reported in the literature.11 Endocarditis as a complication in patients with candidaemia not previously submitted to heart surgery is an uncommon event.5

Of the seven patients with candidaemia, the majority (6/7; 85.7%) received fluconazole as a first-choice antifungal agent. The single untreated patient developed transient candidaemia, recognizable by an episode of shivering and chills following a haemodialysis session, although no subsequent manifestations of invasive fungal disease were reported.

Blood cultures from a patient with chronic renal failure on haemodialysis were positive for C. parapsilosis sensu stricto for nine consecutive months. This patient's clinical condition required haemodialysis via central venous catheter and proved too critical for catheter replacement. Antifungal therapy was therefore maintained, as was the catheter. Previous long-term use of fluconazole by this patient is thought to have facilitated the development of in vitro (MIC=8μg/ml) and in vivo resistance to this antifungal. This was the only patient who evolved to death. Extensive use of fluconazole has been associated with the emergence of resistant clinical isolates.7

Antifungal resistance is an increasing clinical issue, especially in non-C. albicans Candida species, and requires continuous monitoring using susceptibility tests because resistance in vitro can be predictive of treatment failure.13 In the present study, in vitro antifungal susceptibility proved consistent with clinical outcome.

Acknowledgment

Financial support was provided by the Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Estado de Mato Grosso do Sul, Brazil.

References
[1]
B. Almirante, D. Rodríguez, M. Cuenca-Estrella, M. Almela, F. Sanchez, J. Ayats, et al.
Epidemiology, risk factors, and prognosis of Candida parapsilosis bloodstream infections: case–control population-based surveillance study of patients in Barcelona, Spain, from 2002 to 2003.
J Clin Microbiol, 44 (2006), pp. 1681-1685
[2]
M.R. Chang, F.P. Correia, L.C. Costa, P.C.N. Xavier, D.B. Palhares, D.L. Taira, et al.
Candida bloodstream infection: data from a teaching hospital in Mato Grosso do Sul, Brazil.
Rev Inst Med Trop São Paulo, 50 (2008), pp. 265-268
[3]
Clinical and Laboratory Standards Institute (CLSI).
Reference method for broth dilution antifungal susceptibility testing of yeasts: approved standard M27-A3.
3rd ed., Clinical and Laboratory Standards Institute, (2008),
[4]
Clinical and Laboratory Standards Institute (CLSI).
Reference method for broth dilution antifungal susceptibility testing of yeasts: fourth informational supplement M27-S4.
Clinical and Laboratory Standards Institute, (2012),
[5]
A.L. Colombo, T. Guimarães, L.F.A. Camargo, R. Richtmann, F. Queiroz-Telles, M.J.C. Salles.
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.
Braz J Infect Dis, 17 (2013), pp. 283-312
[6]
A. Colombo, M. Garnica, L.F.A. Camargo, C.A. Cunha, A.C. Bandeira, D. Borghi, et al.
Candida glabrata: an emerging pathogen in Brazilian tertiary care hospitals.
[7]
M. Déry, R. Hasbun.
Fluconazole-resistant Candida: mechanisms and risk factor identification.
Curr Fungal Infect Rep, 5 (2011), pp. 23-28
[8]
M. De Toro, M.J. Torres, R. Maite, J. Aznar.
Characterization of Candida parapsilosis complex isolates.
Clin Microbiol Infect, 17 (2010), pp. 418-424
[9]
T.T. Gauna, E. Oshiro, Y.C. Luzio, A.M.M. Paniago, E.R.J.C. Pontes, M.R. Chang.
Bloodstream infection in patients with end-stage renal disease in a teaching hospital in central-western Brazil.
Rev Soc Bras Med Trop, 46 (2013), pp. 426-432
[10]
P.F. Herkert, R.R. Gomes, M.D. Muro, R.L. Pinheiro, G. Fornari, V.A. Vicente, et al.
In vitro susceptibility and molecular characterization of Candida spp. from candidemic patients.
Rev Iberoam Micol, 32 (2015), pp. 221-228
[11]
A. Lefort, L. Chartier, B. Sendid, M. Wolff, J.-L. Mainardi, I. Podglajen, et al.
Diagnosis, management and outcome of Candida endocarditis.
Clin Microbiol Infect, 18 (2012), pp. E99-E109
[12]
G.H. Pereira, P.R. Müller, M.W. Szeszs, A.S.C. Levin, M.S.C. Melhem.
Five-year evaluation of bloodstream yeast infections in a tertiary hospital: the predominance of non-C. albicans Candida species.
Med Mycol, 48 (2010), pp. 839-842
[13]
M.A. Pfaller.
Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment.
Am J Med, 125 (2012), pp. S3-S13
[14]
R.H. Pires, J.M. Santos, J.E. Zaia, C.H.G. Martins, M.J.S. Mendes-Giannini.
Candida parapsilosis complex water isolates from a haemodialysis unit: biofilm production and in vitro evaluation of the use of clinical antifungals.
Mem Inst Oswaldo Cruz, 106 (2011), pp. 646-654
[15]
G. Quindós.
Epidemiology of candidaemia and invasive candidiasis. A changing face.
Rev Iberoam Micol, 31 (2014), pp. 42-48
[16]
J. Sambrook, E.F. Fritsh, T. Maniatis.
Commonly used techniques in molecular cloning.
Molecular cloning. A laboratory manual, appendix E, pp. 3-6
[17]
A. Tavanti, A.D. Davidson, N.A.R. Gow, M.C.J. 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
Copyright © 2016. Asociación Española de Micología
Opciones de artículo
Herramientas
es en pt
Política de cookies Cookies policy Política de cookies
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.