Pruebas de susceptibilidad fúngica frente a antimicóticos

Se analizan las actuales pruebas de susceptibilidad fúngica frente a diversos antimicóticos

Novel strategies to fight Candida species infection

In recent years, there has been a significant increase in the incidence of human fungal infections. The increase in cases of infection caused by Candida species, and the consequent excessive use of antimicrobials, has favored the emergence of resistance to conventional antifungal agents over the past decades. Consequently, Candida infections morbidity and mortality are also increasing. Therefore, new approaches are needed to improve the outcome of patients suffering from Candida infections, because it seems unlikely that the established standard treatments will drastically lower the morbidity of mucocutaneous Candida infections and the high mortality associated with invasive candidiasis. This review aims to present the last advances in the traditional antifungal therapy, and present an overview of novel strategies that are being explored for the treatment of Candida infections, with a special focus on combined antifungal agents, antifungal therapies with alternative compounds (plant extracts and essential oils), adjuvant immunotherapy, photodynamic therapy and laser therapy.Consolidating Research Expertise and Resources on Cellular and Molecular Biotechnology at CEB/IBB’’, Ref. FCOMP-01-0124-FEDER-027462BioHealth – Biotechnology and Bioengineering approaches to improve health quality’’, Ref. NORTE-07-0124-FEDER-000027 co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER

Wild Morchella conica Pers. from different origins: a comparative study of nutritional and bioactive properties

Morchella conica Pers. is a species of fungus that belongs to the Morchellaceae family and was studied in order to obtain more information about this species, by comparing Portuguese and Serbian wild samples. Free sugars, fatty acids, tocopherols, organic and phenolic acids were analysed by chromatographic techniques. M. conica methanolic extracts were tested regarding antioxidant and antimicrobial properties. The absence of hepatotoxicity was confirmed in porcine liver primary cells.The authors are grateful to Fundação para a Ciência e Tecnologia (FCT, Portugal) and COMPETE/QREN/EU for financial support to this work (research project PTDC/AGR-ALI/110062/2009 and BPD/4609/2008 to L. Barros) and to CIMO (strategic project PEst-OE/AGR/UI0690/2011). The authors also thank Serbian Ministry of Education, Science and Technological Development for financial support (grant number 173032)

Multicenter, International Study of MIC/ MEC Distributions for definition of epidemiological cutoff values for sporothrix species identified by molecular methods

Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrix schenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301 Sporothrix schenckii sensu stricto, 486 S. brasiliensis, 75 S. globosa, and 13 S. mexicana molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for S. schenckii and S. brasiliensis, respectively: amphotericin B, 4 and 4 /ml; itraconazole, 2 and 2 μg/ml; posaconazole, 2 and 2 μg/ml; and voriconazole, 64 and 32 μg/ml. Ketoconazole and terbinafine ECVs for S. brasiliensis were 2 and 0.12 μg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for S. schenckii, as well as ECVs for S. globosa and S. mexicana. These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.A. Espinel-Ingroff, D. P. B. Abreu, R. Almeida-Paes, R. S. N. Brilhante, A. Chakrabarti, A. Chowdhary, F. Hagen, S. Córdoba, G. M. Gonzalez, N. P. Govender, J. Guarro, E. M. Johnson, S. E. Kidd, S. A. Pereira, A. M. Rodrigues, S. Rozental, M. W. Szeszs, R. Ballesté Alaniz, A. Bonifaz, L. X. Bonfietti, L. P. Borba-Santos, J. Capilla, A. L. Colombo, M. Dolande, M. G. Isla, M. S. C. Melhem, A. C. Mesa-Arango, M. M. E. Oliveira, M. M. Panizo, Z. Pires de Camargo, R. M. Zancope-Oliveira, J. F. Meis, J. Turnidge

Persistence within dendritic cells marks an antifungal evasion and dissemination strategy of Aspergillus terreus

Aspergillus terreus is an airborne human fungal pathogen causing life-threatening invasive aspergillosis in immunocompromised patients. In contrast to Aspergillus fumigatus, A. terreus infections are associated with high dissemination rates and poor response to antifungal treatment. Here, we compared the interaction of conidia from both fungal species with MUTZ-3-derived dendritic cells (DCs). After phagocytosis, A. fumigatus conidia rapidly escaped from DCs, whereas A. terreus conidia remained persisting with long-term survival. Escape from DCs was independent from DHN-melanin, as A. terreus conidia expressing wA showed no increased intracellular germination. Within DCs A. terreus conidia were protected from antifungals, whereas A. fumigatus conidia were efficiently cleared. Furthermore, while A. fumigatus conidia triggered expression of DC activation markers such as CD80, CD83, CD54, MHCII and CCR7, persistent A. terreus conidia were significantly less immunogenic. Moreover, DCs confronted with A. terreus conidia neither produced pro-inflammatory nor T-cell stimulating cytokines. However, TNF-α addition resulted in activation of DCs and provoked the expression of migration markers without inactivating intracellular A. terreus conidia. Therefore, persistence within DCs and possibly within other immune cells might contribute to the low response of A. terreus infections to antifungal treatment and could be responsible for its high dissemination rates

Repurposing drugs to fast-track therapeutic agents for the treatment of cryptococcosis

Many infectious diseases disproportionately affect people in the developing world. Cryptococcal meningitis is one of the most common mycoses in HIV-AIDS patients, with the highest burden of disease in sub-Saharan Africa. Current best treatment regimens still result in unacceptably high mortality rates, and more effective antifungal agents are needed urgently. Drug development is hampered by the difficulty of developing effective antifungal agents that are not also toxic to human cells, and by a reluctance among pharmaceutical companies to invest in drugs that cannot guarantee a high financial return. Drug repurposing, where existing drugs are screened for alternative activities, is becoming an attractive approach in antimicrobial discovery programs, and various compound libraries are now commercially available. As these drugs have already undergone extensive optimisation and passed regulatory hurdles this can fast-track their progress to market for new uses. This study screened the Screen-Well Enzo library of 640 compounds for candidates that phenotypically inhibited the growth of Cryptococcus deuterogattii. The anthelminthic agent flubendazole, and L-type calcium channel blockers nifedipine, nisoldipine and felodipine, appeared particularly promising and were tested in additional strains and species. Flubendazole was very active against all pathogenic Cryptococcus species, with minimum inhibitory concentrations of 0.039-0.156 μg/mL, and was equally effective against isolates that were resistant to fluconazole. While nifedipine, nisoldipine and felodipine all inhibited Cryptococcus, nisoldipine was also effective against Candida, Saccharomyces and Aspergillus. This study validates repurposing as a rapid approach for finding new agents to treat neglected infectious diseases

Statistical analyses of correlation between fluconazole MICs for Candida spp. assessed by standard methods set forth by the European Committee on Antimicrobial Susceptibility Testing (E.Dis. 7.1) and CLSI (M27-A2).

The European Committee on Antimicrobial Susceptibility Testing (EUCAST) Subcommittee on Antifungal Susceptibility Testing recently published a standard for determining the susceptibility of fermentative yeasts to antifungals. From the beginning, the EUCAST and its North American counterpart, the CLSI, decided to work together in order to establish common standards. As part of this exercise, the susceptibility of a set of 475 yeast isolates was tested by both standards. The intraclass correlation coefficient and the equations defining the linear regression between both methods were estimated. Both methods produced very similar results, with an intraclass correlation coefficient of 0.954 (0.945 to 0.962), although linear regression analysis shows that the EUCAST standard resulted in slightly lower MICs. There were only eight isolates showing at least four twofold dilution MIC differences between both standards. After 24 h of incubation, the MICs obtained by the CLSI method were equivalent to those obtained by the EUCAST standard. In summary, both methods produce very similar MICs, indicating that methodology does not pose any obstacle to obtaining uniform standards for antifungal susceptibility testing of yeast

Intravenous micafungin versus voriconazole for chronic pulmonary aspergillosis: A multicenter trial in Japan.

Chronic pulmonary aspergillosis (CPA) is slowly progressive inflammatory pulmonary syndrome due to Aspergillus spp. The evidence regarding CPA treatment is limited. We conducted a randomized, multicenter, open-label trial comparing intravenous micafungin (MCFG) of 150-300 mg once daily with intravenous voriconazole (VRCZ) of 6 mg/kg twice on Day 1 followed by 4 mg/kg twice daily for the treatment of 107 in patients with CPA to compare the efficacy and safety of both drugs as initial treatment in Japan. Treatment effectiveness was defined by clinical, mycological, radiological and serological responses 2 weeks after the initial administration and at the end of therapy. The total of 50 and 47 patients were assigned to the MCFG and VRCZ groups, respectively. The difference in efficacy rates between MCFG and VRCZ was not significant, either after 2 weeks [68.0% vs. 58.7%; the absolute difference, 9.3% with a 95% confidence interval (CI), -9.97 to 28.58, P = 0.344] or at the end of therapy (60.0% vs. 53.2%; the absolute difference, 6.8% with a 95% CI, -12.92 to 26.54, P = 0.499). In the safety evaluation, fewer adverse events occurred in the MCFG than VRCZ group (26.4% vs. 61.1%, P = 0.0004). MCFG was as effective as VRCZ and significantly safer than as an initial treatment of CPA. (UMIN Clinical Trials Registry number, UMIN000001786.)