In vitro inhibitory activity of sertraline against clinical isolates of Sporothrix schenckii / Actividad inhibitoria in vitro de la sertralina frente a aislamientos clínicos de Sporothrix schenckii

Background: Sertraline (SRT) is an antidepressant that has proven its activity in vitro against Cryptococcus, Coccidioides, Trichosporon and other fungi. Disseminated sporotrichosis, although rare, has a high mortality and its treatment is difficult and prolonged, often relying in combining two or more antifungals. Aims: In our study we evaluate the antifungal activity of SRT, alone and in combination with itraconazole (ITC), voriconazole (VRC) and amphotericin B (AMB), against 15 clinical isolates of Sporothrix schenckii. Methods: We used the broth microdilution method as described by the CLSI to test the susceptibility to antifungals, and the checkerboard microdilution method to evaluate drug interactions. Results: The minimum inhibitory concentration (MIC) with SRT was in the range of 4-8μg/ml, while for AMB, VRC and ITC were 0.5-4μg/ml, 0.5-8μg/ml and 0.125-2μg/ml, respectively. In addition, SRT showed synergy with ITC in one strain, mainly additivity with VRC, and indifference with AMB in others. Conclusions: The MIC values with SRT for the isolates studied show the potential role of this drug as an adjuvant in the treatment of sporotrichosis, especially in disseminated or complicated cases

Antecedentes: La sertralina (SRT) es un antidepresivo que ha demostrado actividad in vitro contra Cryptococcus, Coccidioides, Trichosporon y otros hongos. La esporotricosis diseminada, aunque rara, tiene una mortalidad elevada y su tratamiento es complicado, requiriendo, a menudo, la combinación de dos o más antifúngicos. Objetivos: En este estudio evaluamos la actividad antifúngica de SRT, sola y en combinación con itraconazol (ITC), voriconazol (VRC) y anfotericina B (AMB), frente a 15 aislamientos clínicos de Sporothrix schenckii. Métodos: Se usó la técnica de microdilución en caldo para evaluar la sensibilidad a los antifúngicos y el método de tablero de damas para las interacciones entre estos fármacos. Resultados: La concentración mínima inhibitoria (CMI) de SRT estuvo en el rango de 4-8μg/ml, mientras que para AMB, VRC e ITC fue de 0,5-4 μg/ml, 0,5-8 μg/ml y 0,125-2 μg/ml, respectivamente. La SRT mostró sinergia con ITC frente a una cepa, efecto aditivo principalmente con VRC, e indiferencia con AMB. Conclusiones: Los valores de la CMI de SRT para los aislamientos ensayados son indicativos del potencial de este fármaco como adyuvante en el tratamiento de la esporotricosis, especialmente en casos complicados o de enfermedad diseminada

In vitro inhibitory activity of sertraline against clinical isolates of Sporothrix schenckii.

BACKGROUND: Sertraline (SRT) is an antidepressant that has proven its activity in vitro against Cryptococcus, Coccidioides, Trichosporon and other fungi. Disseminated sporotrichosis, although rare, has a high mortality and its treatment is difficult and prolonged, often relying in combining two or more antifungals. AIMS: In our study we evaluate the antifungal activity of SRT, alone and in combination with itraconazole (ITC), voriconazole (VRC) and amphotericin B (AMB), against 15 clinical isolates of Sporothrix schenckii. METHODS: We used the broth microdilution method as described by the CLSI to test the susceptibility to antifungals, and the checkerboard microdilution method to evaluate drug interactions. RESULTS: The minimum inhibitory concentration (MIC) with SRT was in the range of 4-8µg/ml, while for AMB, VRC and ITC were 0.5-4µg/ml, 0.5-8µg/ml and 0.125-2µg/ml, respectively. In addition, SRT showed synergy with ITC in one strain, mainly additivity with VRC, and indifference with AMB in others. CONCLUSIONS: The MIC values with SRT for the isolates studied show the potential role of this drug as an adjuvant in the treatment of sporotrichosis, especially in disseminated or complicated cases.

Association between Candida biofilm-forming bloodstream isolates and the clinical evolution in patients with candidemia: An observational nine-year single center study in Mexico / Asociación entre aislamientos sanguíneos de Candida formadores de biopelícula y la evolución clínica en pacientes con candidemia: un estudio observacional monocéntrico de nueve años en México

Background. Candidemia is one of the most common nosocomial infections globally and it is associated with considerable excess mortality and costs. Abreast, biofilm-forming strains are associated with even higher mortality rates and poor prognosis for the patient. Aims. To evaluate a possible association between the biofilm-forming capability of Candida bloodstream isolates and the clinical evolution in patients with candidemia. Methods. An observational, retrospective study was conducted at a tertiary care university hospital during 9 years (2006-2015). The biofilm quantitation of the Candida bloodstream isolates was determined by crystal violet staining and XTT reduction assay. Results. A total of 218 cases of candidemia had been diagnosed and 89 isolates were obtained. The mortality rate was 36% and the main risk factors were antibiotic exposure and the use of catheters. Candida tropicalis (52.8%) was the most frequent species, followed by Candida albicans (30.4%), Candida parapsilosis sensu stricto (10.1%), Candida orthopsilosis (3.4%), Candida krusei (2.2%) and Candida glabrata sensu stricto (1.1%). All the strains were biofilm producers, which is an important contribution to the patient's mortality. C. tropicalis showed the highest production of biomass biofilm, whereas C. glabrata exhibited the highest metabolic activity. Conclusions. This study contributes to expand the knowledge about the local epidemiology of candidemia and highlights the impact of Candida biofilm on patient's outcome (AU)

Antecedentes. La candidemia es una de las infecciones nosocomiales más frecuentes globalmente y se encuentra asociada con una elevada mortalidad y coste económico. Las cepas productoras de biopelícula se asocian con elevadas tasas de mortalidad y mal pronóstico para el paciente. Objetivos. Evaluar una posible asociación entre la capacidad de formación de biopelícula de aislamientos sanguíneos de Candida y la evolución clínica de pacientes con candidemia. Métodos. Durante 9 años (2006-2015) se ha llevado a cabo un estudio observacional y retrospectivo en un hospital universitario de tercer nivel de atención. La cuantificación de biopelícula de los aislamientos sanguíneos de Candida se determinó por tinción con cristal violeta y ensayo de reducción de XTT. Resultados. Se diagnosticó un total de 218 casos de candidemia y se obtuvieron 89 aislamientos. La tasa de mortalidad fue del 36% y los principales factores de riesgo fueron la exposición a antibióticos y el uso de catéteres. Candida tropicalis (52,8%) fue la especie más frecuente, seguida por Candida albicans (30,4%), Candida parapsilosis sensu stricto (10,1%), Candida orthopsilosis (3,4%), Candida krusei (2,2%) y Candida glabrata sensu stricto (1,1%). Todas las cepas produjeron biopelícula, una contribución importante a la mortalidad de los pacientes. C. tropicalis mostró la producción más alta de biomasa de biopelícula, mientras que C. glabrata exhibió la actividad metabólica más alta. onclusiones. Este estudio contribuye a expandir el conocimiento de la epidemiología local de la candidemia y resalta el impacto de las biopelículas de Candida en el pronóstico del paciente (AU)

Clinical evaluation of the antifungal effect of sertraline in the treatment of cryptococcal meningitis in HIV patients: a single Mexican center experience.

PURPOSE: Cryptococcal meningitis is a potentially fatal fungal infection associated with a significant attributable morbidity and mortality, especially among HIV/AIDS patients. The first-line therapy for the treatment of this clinical entity is the combinatory therapy of amphotericin B plus flucytosine. However, the high cost, toxic effects, and limited repertoire of effective antifungal drugs have led to the investigation of novel molecules. This is a prospective, double-blinded, and randomized study performed in a Mexican tertiary care center to evaluate the antifungal activity of sertraline in the treatment of cryptococcal meningitis in HIV patients. METHODS: During June 2015-December 2016, patients were recruited and included in one of two study groups: group A was given standard antifungal treatment plus sertraline 200 mg/day, while group B was given standard antifungal plus placebo. Lumbar punctures were performed on days 0, 7, and 14 of the study, and cryptococcal antigenemia and quantitative fungal culture in cerebrospinal fluid at each time point were evaluated to measure the rate of fungal clearance. RESULTS: The fungal loads and cryptococcal antigenemia titers showed a marked tendency to decrease by day 14 in both groups. Otherwise, group B exhibited a slightly higher nonstatistical rate of fungal clearance (-0.2868 ± 0.08275 log CFU/ml/day) than group A (-0.2496 ± 0.08340 log CFU/ml/day). CONCLUSIONS: A statistical difference between study groups was not found. This is the first study in Latin America that reports the experience of using sertraline as an adjuvant in the antifungal management of cryptococcal meningitis in HIV patients.

Association between Candida biofilm-forming bloodstream isolates and the clinical evolution in patients with candidemia: An observational nine-year single center study in Mexico.

BACKGROUND: Candidemia is one of the most common nosocomial infections globally and it is associated with considerable excess mortality and costs. Abreast, biofilm-forming strains are associated with even higher mortality rates and poor prognosis for the patient. AIMS: To evaluate a possible association between the biofilm-forming capability of Candida bloodstream isolates and the clinical evolution in patients with candidemia. METHODS: An observational, retrospective study was conducted at a tertiary care university hospital during 9 years (2006-2015). The biofilm quantitation of the Candida bloodstream isolates was determined by crystal violet staining and XTT reduction assay. RESULTS: A total of 218 cases of candidemia had been diagnosed and 89 isolates were obtained. The mortality rate was 36% and the main risk factors were antibiotic exposure and the use of catheters. Candida tropicalis (52.8%) was the most frequent species, followed by Candida albicans (30.4%), Candida parapsilosis sensu stricto (10.1%), Candida orthopsilosis (3.4%), Candida krusei (2.2%) and Candida glabrata sensu stricto (1.1%). All the strains were biofilm producers, which is an important contribution to the patient's mortality. C. tropicalis showed the highest production of biomass biofilm, whereas C. glabrata exhibited the highest metabolic activity. CONCLUSIONS: This study contributes to expand the knowledge about the local epidemiology of candidemia and highlights the impact of Candida biofilm on patient's outcome.

Activity of sertraline against Cryptococcus neoformans: in vitro and in vivo assays.

Cryptococcus neoformans infection is an important cause of meningitis in HIV/AIDS endemic regions. Antifungals for its management include amphotericin B, flucytosine, and fluconazole. Recently, treatment of this mycosis with sertraline has been studied with variable clinical outcomes. The aim of the study was to assess the in vitro antifungal effect of sertraline against clinical isolates of Cryptococcus spp. as well as its in vivo activity in a murine model of cryptococcal meningoencephalitis. The in vitro susceptibility to fluconazole, amphotericin B, voriconazole and sertraline of 153 Cryptococcus spp. strains were evaluated according to CLSI procedures. Fungal tissue burden, serum antigenaemia and histopathology, together with the therapeutic efficacy of amphotericin B (3 mg/kg), fluconazole (15 mg/kg), and sertraline (3, 10, and 15 mg/kg) were evaluated in mice intracranially inoculated with one isolate of Cryptococcus neoformans. All strains were susceptible to the antifungals studied and exhibited growth inhibition with sertraline at clinically relevant concentrations. Sertraline at a dose of 15 mg/kg reduced the fungal burden in the brain and spleen with an efficacy comparable to that of fluconazole. In conclusion, sertraline exhibited an excellent in vitro-in vivo anti-cryptococcal activity, representing a possible new alternative for the clinical management of meningeal cryptococcosis.

Case of chromoblastomycosis with pulmonary involvement.

Chromoblastomycosis is a slowly growing chronic cutaneous mycosis associated with a variety of cutaneous lesions. Extra-dermal involvement is rare. A 58-year-old man was admitted to the hospital with nausea, vomiting, weakness and a history of weight loss. On inspection, he had a large verrucous mass in the sacral region, and two large subcutaneous nodules in the anterior thoracic wall. He claimed the lesions were several years old. Biopsy and histological studies were positive for chromoblastomycosis. Routine chest radiography showed hilar enlargement, and a chest computed tomography was ordered. Pulmonary nodules were evident, and endoscopically acquired samples were also positive for chromoblastomycosis. Extra-dermal and systemic involvement in chromoblastomycosis is exceedingly rare and often associated with immunosuppression. There is only one other case of pulmonary chromoblastomycosis reported in the published work.