The First Korean Case of Candidemia due to Candida dubliniensis

Candidemia due to uncommon Candida spp. appears to be increasing in incidence. C. dubliniensis has been increasingly recovered from individuals not infected with HIV. Identification of C. dubliniensis can be problematic in routine clinical practice due to its phenotypic resemblance to C. albicans. We report the first case of C. dubliniensis candidemia in Korea, which occurred in a 64-yr-old woman who presented with partial seizure, drowsiness, and recurrent fever. Germ-tube positive yeast that was isolated from blood and central venous catheter tip cultures formed smooth, white colonies on sheep blood agar and Sabouraud agar plates, indicative of Candida spp. C. dubliniensis was identified using the Vitek 2 system (bioMerieux, USA), latex agglutination, chromogenic agar, and multiplex PCR. The blood isolate was susceptible to flucytosine, fluconazole, voriconazole, and amphotericin B. After removal of the central venous catheter and initiation of fluconazole treatment, the patient's condition gradually improved, and she was cleared for discharge from our hospital. Both clinicians and microbiologists should be aware of predisposing factors to C. dubliniensis candidemia in order to promote early diagnosis and appropriate treatment.

Evaluación de tres métodos para la detección de la sensibilidad in vitro de especies de Candida a los antifúngicos / Evaluation of three methods for in vitro detection of antifungal susceptibility of Candida species

Los métodos de referencia E. Def 7.1 y M27-A3, que detectan resistencia in vitro a los antifúngicos, son onerosos y muy laboriosos, por lo que su implementación en los laboratorios hospitalarios es limitada. Existen técnicas comerciales de simple realización, que permitirían obtener resultados comparables a los que se obtienen con los métodos estándares. Los objetivos de esta investigación fueron: a) comparar los resultados de concentración inhibitoria mínima obtenidos según el método de referencia E.Def 7.1 con los obtenidos mediante el empleo del equipo comercial ATB® Fungus 3 en un conjunto de 82 aislamientos clínicos de Candida spp. frente a los siguientes antifúngicos: anfotericina B, 5-fluorocitosina, fluconazol e itraconazol; b) comparar en ese mismo conjunto de aislamientos los resultados del estudio de sensibilidad al fluconazol por difusión en agar empleando tabletas Neo-SensitabsTM o discos Malbrán con los que se obtienen por el método de referencia. La concordancia general entre el método de referencia y el ATB® Fungus 3 fue del 90,2 %, mientras que la concordancia del método de referencia con los métodos por difusión con discos y con tabletas alcanzó el 96,3% y el 92,7 %, respectivamente. El ATB® Fungus 3 fue eficaz para determinar la sensibilidad a la anfotericina B y a la 5-fluorocitosina, pero se observaron discrepancias al evaluar la sensibilidad a los azoles. Los métodos por difusión resultaron útiles para determinar la sensibilidad al fluconazol; sin embargo, observamos 3 discrepancias muy mayores, 1 mayor y 2 menores con el método de difusión con tabletas, mientras que con los discos solo se produjeron 3 discrepancias menores.

Reference methods E.Def 7.1 and M27-A3 detect in vitro resistance; however, they are expensive and very laborious. Thus, their actual use in hospital laboratories is limited. There are commercial techniques available, having easier accessibility and development, which would yield results comparable to those of the reference methods. The objectives of this study were: a) to compare the results of minimal inhibitory concentration of 82 Candida spp. clinic isolates according to reference method E.Def 7.1 and ATB® Fungus 3; b) to compare the results of fluconazole susceptibility testing by disk diffusion in agar with Neo-SensitabsTM tablets and Malbrán disks with those of the reference methods. Minimal inhibitory concentration for amphotericin B, 5-flucytosine, fluconazole and itraconazole was performed according to the E.Def 7.1 and the ATB Fungus 3 methods and diffusion was carried out with fluconazole disks and tablets. General concordance between the reference method and ATB Fungus 3 was 90.2 % and 96.3 and 92.7% for diffusion with disks and tablets. The ATB Fungus 3 method was effective to determine susceptibility against amphotericin B and 5-flucytosine; however, discrepancies were observed with azole drugs. Disk diffusion methods are useful to determine susceptibility to fluconazole; however, 3 very major, 1 major and 2 minor errors were observed with the tablets, whereas only 3 minor errors were observed with the disks.

In vitro antifungal susceptibility of Candida spp. oral isolates from HIV-positive patients and control individuals

Oropharyngeal candidiasis is the most common fungal infection among HIV-positive patients. This condition can be treated with either systemic or topical antifungal agents; treatments are usually indicated empirically on the basis of clinical data. The knowledge of in vitro antifungal susceptibility is important to determine correct therapeutic guides for the treatment of fungal infections. Therefore, the objective of this study was to determine the antifungal susceptibility profile of oral Candida isolates from HIV-positive patients and control individuals. Amphotericin B, fluconazole, flucytosine, nystatin and ketoconazole were tested according to the methodology of microdilution proposed by the Clinical and Laboratory Standards Institute (CLSI); results were recorded in values of minimal inhibitory concentration (MIC). A total of 71 Candida isolates from HIV-positive patients were examined with the following species represented: C. albicans (59), C. tropicalis (9), C. glabrata (1), C. guilliermondii (1) and C. krusei (1). A total of 15 Candida isolates were evaluated from control individuals comprised of 11 C. albicans and 4 C. tropicalis samples. Our results demonstrated that the tested antifungal agents showed good activity for most isolates from both groups; however, variability in MIC values among isolates was observed.

Genotyping of the MTL loci and susceptibility to two antifungal agents of Candida glabrata clinical isolates

The opportunistic fungal pathogen Candida glabrata is the second most common isolate from bloodstream infections worldwide and is naturally less susceptible to the antifungal drug fluconazole than other Candida species. C. glabrata is a haploid yeast that contains three mating-type like loci (MTL), although no sexual cycle has been described. Strains containing both types of mating information at the MTL1 locus are found in clinical isolates, but it is thought that strains containing type a information are more common. Here we investigated if a particular combination of mating type information at each MTLlocus is more prevalent in clinical isolates from hospitalized patients in Mexico and if there is a correlation between mating information and resistance to fluconazole and 5-fluorocytosine. We found that while both types of information at MTL1 are equally represented in a collection of 64 clinical isolates, the vast majority of isolates contain a-type information at MTL2 and α-type at MTL3. We also found no correlation of the particular combination of mating type information at the three MTL loci and resistance to fluconazole.

Antimicóticos en niños / Antifungals in Children

Las micosis superficiales son padecimientos frecuentes en la infancia y para su manejo se pueden utilizar antimicóticos tanto tópicos como sistémicos. Sin embargo, en las últimas décadas, ha aumentado la población infantil susceptible a infecciones diseminadas o sistémicas por agentes oportunistas que ponen en riesgo la vida. Las principales son la candidosis y la aspergilosis. Se han desarrollado nuevos antimicóticos con espectros más amplios de acción y menor toxicidad, pero la mayoría de los reportes en la literatura se refieren a estudios hechos en adultos, cuyos resultados son extrapolados a la población pediátrica. La presente revisión tiene como objetivo condensar la información referente al uso de antimicóticos en niños, con énfasis en las diferencias farmacocinéticas con respecto a los adultos y las indicaciones principales para su uso (AU)

Superficial mycoses are common in childhood, either topical or systemic antifungals can be used for treatment. However, in the past decade, the pediatric population at risk of a disseminated or systemic infection by opportunistic fungi has increased. The most important are candidiasis and aspergillosis. New antifungals, with a wider spectrum of action and less toxicity have been developed, nevertheless, most of the studies and reports of the literature focus on adults and the findings are extrapolated to children. The objective of this paper is to review what has been published on the use of antifungals in the pediatric age, focusing in pharmacokinetic differences regarding adults and current indications for this group of drugs (AU)

In vitro susceptibility to antifungal agents of environmental Cryptococcus spp. isolated in the city of Ribeirão Preto, São Paulo, Brazil

Infections by Cryptococcus strains other than C. neoformans have been detected in immunocompromised patients. Of these strains, three are considered human pathogens: C. albidus, C. laurenttii, and C. uniguttulatus. This study deals with the in vitro susceptibility of Cryptococcus to drugs such as amphotericin B, itraconazole, fluconazole, and 5-fluorocytosine. Environmental Cryptococcus isolates (50) distributed as follows: C. neoformans var. neoformans (16), C. albidus (17), C. laurentii (14), and C. uniguttulatus (3) were evaluated by the micro and macrodilution techniques, according to EUCAST and NCCLS recommendations, respectively. Considering both methodologies the respective minimal inhibitory concentrations (MIC) were 0.125 and 2 æg/ml for amphotericin B, 0.06 and 8 æg/ml for itraconazole, and 0.5 and more than 64 æg/ml for fluconazole and 5-fluorocytosine. Agreement percentages for the two methodologies were 100 percent for amphotericin B and fluconazole for all the strains tested. For itraconazole, the agreement percentage was 81.3 percent in the C. neoformans strain and 100 percent for all the others. All species had a agreement percentage of 94.1 to 100 percent when susceptibility to 5-fluorocytosine was tested. It is concluded that environmental isolates of C. neoformans var. neoformans, C. albidus, C. laurentii, and C. uniguttulatus may show high MICs against certain drugs, suggesting in vitro primary resistance to the antifungals tested.

In vitro antifungal susceptibility of Candida spp. isolates from patients with chronic periodontitis and from control patients

Em certas situações, tal como em pacientes imunocomprometidos, superinfecção por Candida pode ocorrer e ser refratária ao tratamento periodontal convencional. Nesses casos, a terapia sistêmica com antifúngicos pode ser indicada. O objetivo deste trabalho foi estudar a suscetibilidade aos antifúngicos de cepas de leveduras do gênero Candida isoladas de pacientes com periodontite crônica e de indivíduos controle. Um total de 39 isolados de C. albicans, 9 de C. tropicalis, 2 de C. glabrata e 5 de Candida spp. provenientes de indivíduos controle e 30 de C. albicans, 3 de C. tropicalis e 2 de C. glabrata de pacientes com periodontite foram testados. No grupo controle, uma amostra de C. glabrata foi resistente ao cetoconazol e uma de Candida spp. mostrou-se resistente a anfotericina B, cetoconazol e miconazol. Dentre as amostras do grupo com periodontite, uma (3,33%) amostra de C. albicans foi resistente à 5-fluorocitosina e ao cetoconazol. A partir dos resultados obtidos, concluiu-se que fluconazol foi o fármaco mais eficaz contra as várias espécies de Candida estudadas. Não foram observadas diferenças expressivas na sensibilidade de isolados de pacientes com periodontite e de indivíduos controle.

Antifungal drug combinations for Cryptococcus neoformans and Prototheca spp.

Seventy-one isolates of Cryptococcus neoformans and 5 isolates of Prototheca spp. were tested for in vitro susceptibility against amphotericin B alone and against the combination of amphotericin B with each clinically relevant concentration of flucytosine (5-FC) and rifampin by broth dilution methods. The combinations of amphotericin B and rifampin produced greater effect on reduction of the minimal inhibition concentration (MIC) of amphotericin B than did either drug used individually. Flucytosine combined with amphotericin B produced little or no reduction of the MIC compared with amphotericin B alone.

Criptococose: tratamento prognóstico e prevençäo / Cryptococosis: treatment, prognostic and prevention

O tratamento da criptococose depende do tecido envolvido, da doença predisponente, do mecanismo de defesa do hospedeiro e dos achados liquóricos e sorológicos. O tratamento de escolha para a meningite criptococócica é a combinaçäo de anfotericina B e 5-flucitosina. O fluconazol, das novas drogas, é a atual indicaçäo para o tratamento de manutençäo, por sua açäo antifúngica e penetraçäo no sistema nervoso central

Susceptibilidad "in vitro" de cepas de Cryptococcus a 5 drogas antifúngicas / In vitro susceptibility of Cryptococcus strains to 5 antifungal drugs

Se estudió la susceptibilidad "in vitro" de 24 cepas de 3 espécies del género Cryptococcus a 5 drogas antifúngicas (antrotericina B, 5 fluorocitosina, ketoconazol, itraconazol y miconazol). Las mismas se agruparon según su especie, variedad y origen de aislamiento. Para determinar la concentración inhibitoria mínima (C.I.M.) de cada droga se empleó el método de dilución en agar con el medio básico nitrogenado para levaduras, adicionado de glucosa. Se obtuvo además la media geométrica de estos valores para cada grupo y se comparó cada uno de ellos. Los resultados obtenido fueron homogéneos con la sola excepción de las cepas de Cryptococcus sp (no neoformans), en las cuales se detectaron elevados valores de C.I.M. para la 5 fluorocitosina

Avances en la Quimioterapia de las Micosis Sistemicas / Advances in Pharmacotherapy of Systemic Mycoses

Se presenta una revision sobre las drogas que se pueden emplear para el tratamiento de las micosis sistemicas. Se analiza brevemente el mecanismo de accion de la anfotericina B, la 5-fluorocitosina y los imidazoles miconazol y ketoconazol. Se ofrecen datos sobre los resultados de las terapias recomendadas por grupos medicos internacionales y se mencionan los avances recientes de laboratorio que permitan determinar in vitro la susceptibilidad de los agentes y la concentracion serica del farmaco