Invasive pulmonary aspergillosis is a life-threatening fungal disease principally caused by the ubiquitous mould Aspergillus fumigatus. This clinical entity is a major cause of morbidity and mortality (principally, but not restricted to, immunocompromised individuals). A few recent reports suggest in vitro fungicidal activity of sertraline against Aspergillus spp., but this activity has not yet been investigated in vivo. To evaluate the antifungal activity of sertraline in two in vivo models of aspergillosis. The antifungal activity of sertraline as monotherapy at three different doses (3, 10 and 15 mg/kg) was evaluated in Galleria mellonella and in a murine model of invasive pulmonary aspergillosis. Therapeutic efficacy parameters determined were larval survival and health index score for G. mellonella, whereas pulmonary fungal burden, galactomannan and lung histopathology were assessed in the murine model. Sertraline treatments improved larval survival and health index score, especially at doses of 10 and 15 mg/kg. Moreover, 10 mg/kg sertraline was able to reduce pulmonary fungal burden with an efficacy comparable with that of 3 mg/kg amphotericin B and 10 mg/kg voriconazole. To the best of our knowledge, this is the first in vivo study that evaluates the antifungal activity of sertraline against A. fumigatus, showing a possible promising option for the adjuvant treatment of pulmonary aspergillosis.
The genus Scedosporium is a complex of ubiquitous moulds associated with a wide spectrum of clinical entities, with high mortality principally in immunocompromised hosts. Ecology of these microorganisms has been studied performing isolations from environmental sources, showing a preference for human-impacted environments. This study aimed to evaluate the presence and antifungal susceptibility of Scedosporium complex species in soil samples collected in high-human-activity sites of Mexico. A total of 97 soil samples from 25 Mexican states were collected. Identifications were performed by microscopic morphology and confirmed by sequencing of the rDNA (internal transcribed spacer [ITS], D1/D2) and β-tubulin partial loci. Antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) protocols. Soil samples of urban gardens and industrial parks constituted the best sources for isolation of Scedosporium complex species. S. apiospermum sensu stricto was the most prevalent species (69%), followed by S. boydii (16%). Voriconazole (minimal inhibitory concentration [MIC] geometric mean ≤2.08 µg/mL), followed by posaconazole (MIC geometric mean ≤2.64 µg/mL), exhibited excellent in vitro activity for most species. Amphotericin B and fluconazole demonstrated limited antifungal activity, and all of the strains were resistant to echinocandins. This is the first report in Mexico of environmental distribution and antifungal in vitro susceptibility of these emergent pathogens.
1 October 2009 in Antimicrobial Agents and Chemotherapy
The efficacy of albaconazole (ABC) was evaluated using a murine model of vaginal Candida albicans infection. Both ABC and fluconazole (FLC) were effective in reducing the fungal load from vaginas of infected mice; however, ABC demonstrated encouraging activities against an FLC-resistant strain, with trends toward superiority over FLC in some treatment groups.
The Scedosporium genus is an emerging pathogen with worldwide prevalence and high mortality rates that gives multidrug resistance to antifungals; therefore, pharmacological alternatives must be sought for the treatment of diseases caused by this fungus. In the present project, six new α-aminophosphates were synthesized by the Kabachnik–Fields multicomponent reaction by vortex agitation, and six new monohydrolyzed α-aminophosphonic acids were synthesized by an alkaline hydrolysis reaction. Antifungal activity was evaluated using the agar diffusion method as an initial screening to determine the most active compound compared to voriconazole; then it was evaluated against 23 strains of the genus Scedosporium following the M38-A2 protocol from CLSI (activity range: 648.76–700 µg/mL). Results showed that compound 5f exhibited the highest antifungal activity according to the agar diffusion method (≤1 mg/mL). Cytotoxicity against healthy COS-7 cells was also evaluated by the MTT assay and it was shown that compound 5f exhibits a lower toxicity in comparison to voriconazole at the same concentration (1000 µM). A docking study was conducted afterwards, showing that the possible mechanism of action of the compound is through the inhibition of allosteric 14-α-demethylase. Taking these results as a basis, 5f is presented as a compound with attractive properties for further studies.
Biological and non-biological aerosols are always present. According to the World Health Organization (WHO), air pollution is responsible for seven million deaths every year. The dynamics of airborne fungi and their association with air pollutants over time show mixed results. In this study, we sampled 50 L of air daily for a period of 12 months (February 2022–January 2023) in downtown Monterrey, Mexico to evaluate the presence of culturable fungi. May, October, November, and December were the months with the highest concentration of fungi with a significant difference from the rest of the months. Cladosporium was the predominant fungus in the air for every month except for September. Aspergillus, Fusarium, and Penicillium followed Cladosporium as the genera with the highest concentration. PM10, PM2.5, and NO2 were the most abundant pollutants, with levels above the recommended guidelines in practically every month studied. Cladosporium was the only fungus showing an inverse correlation with PM10 and PM2.5 in February, April, and May. It also showed an inverse correlation with NO, NO2, and NOx in February, March, and April. Aspergillus, Alternaria, Fusarium, and Penicillium had mixed correlations with pollutants. Yeasts showed no correlation with PM10 or PM2.5 but showed inverse correlations with nitrogen-based pollutants.
31 January 2018 in Revista Iberoamericana de Micologia