Activity of antifungal agents alone and in combination against echinocandin-susceptible and -resistant Candida parapsilosis strains.

BACKGROUND: Candida parapsilosis may acquire resistance to echinocandins, a fact that prompts the search for new therapeutic options. AIMS: The present study aimed to evaluate the in vitro activity of antifungal agents, alone and in combination, against four groups of C. parapsilosis strains: (1) echinocandin-susceptible (ES) clinical isolates (MIC ≤ 2µg/ml), (2) anidulafungin-resistant strains (MIC ≥ 8µg/ml), (3) caspofungin-resistant strains (MIC ≥ 8µg/ml), and (4) micafungin-resistant strains (MIC ≥ 8µg/ml). METHODS: Antifungal interactions were evaluated by a checkerboard micro-dilution method. The determination of the MIC to each drug for every isolate according to the Clinical and Laboratory Standards Institute documents M27 (2017) and M60 (2017) was also done. RESULTS: The echinocandins-resistant (ER) strains showed higher MICs to the tested antifungals than the ES strains, except for amphotericin B, for which the ER groups remained susceptible. CONCLUSIONS: Most combinations showed indifferent interactions. The use of monotherapy still seems to be the best option. As resistance to echinocandins is an emergent phenomenon, further studies are required to provide clearer information on the susceptibility differences between strains to these antifungal agents.

Do antibacterial and antifungal combinations have better activity against clinically relevant fusarium species? in vitro synergism.

The aim of this study was to evaluate the susceptibility of 20 clinical isolates of Fusarium spp. to classic antifungals [amphotericin B (AmB), itraconazole (ITR), voriconazole (VRC) and caspofungin (CAS)] and to non-antifungal agents [amiodarone (AMD), doxycycline (DOX) and moxifloxacin (MFX)] by the broth microdilution method. Combinations between these antifungal and non-antifungal agents were also evaluated to determine the fractional inhibitory concentration indices using the chequerboard technique. Synergistic interactions were observed for the following combinations (% synergism): AMD + VRC, 80%; MFX + AmB, 75%; AMD + AmB, 65%; DOX + VRC, 60%; MFX + VRC, 55%; DOX + AmB, 50%; and AMD + CAS, 30%. Synergism was not observed for associations with ITR. Antagonism was not seen in any combination. These findings suggest that the combinations of AMD, DOX or MFX with AmB or VRC to have potential for future in vivo investigations.

Exploring the In Vitro Resistance of Candida parapsilosis to Echinocandins.

The naturally high minimum inhibitory concentration exhibited by echinocandins against Candida parapsilosis has been known since the first introduction of these antifungal agents. Despite this awareness, clinical failures have not been reported; consequently, the resistance of C. parapsilosis to echinocandins remains unexplored. We exposed 30 isolates of C. parapsilosis to echinocandins (caspofungin, micafungin, and anidulafungin) in vitro and studied the effects of this exposure. After 60 exposures, 80, 67, and 60 % of the isolates changed from susceptible to non-susceptible to caspofungin, micafungin, and anidulafungin, respectively. In addition, four strains exhibited cross-resistance to all three echinocandins. Based on the M27-A3 (CLSI, 2008) and M27-S4 (CLSI, 2012) techniques, the susceptibility of the resistant strains to other antifungal agents was assayed. All of the tested echinocandin-resistant strains were susceptible to amphotericin B, and the resistance rate to fluconazole, voriconazole, and flucytosine was 73.3, 43.3, and 20 %, respectively. The exposure of C. parapsilosis to the three echinocandins generated cross-resistant strains and an unexpected in vitro resistance to azoles and flucytosine.

Antifungal activities of diphenyl diselenide and ebselen alone and in combination with antifungal agents against Fusarium spp.

Herein, we describe the in vitro activity of a combination of the organoselenium compounds diphenyl diselenide and ebselen alone and in combination with amphotericin B, caspofungin, itraconazole, and voriconazole against 25 clinical isolates of Fusarium spp. For this analysis, we used the broth microdilution method based on the M38-A2 technique and checkerboard microdilution method. Diphenyl diselenide (MIC range = 4-32 µg/ml) and ebselen (MIC range = 2-8 µg/ml) showed in vitro activity against the isolates tested. The most effective combinations were (synergism rates): ebselen + amphotericin B (88%), ebselen + voriconazole (80%), diphenyl diselenide + amphotericin B (72%), and diphenyl diselenide + voriconazole (64%). Combination with caspofungin resulted in low rates of synergism: ebselen + caspofungin, 36%, and diphenyl diselenide + caspofungin, 28%; combination with itraconazole demonstrated indifferent interactions. Antagonistic effects were not observed for any of the combinations tested. Our findings suggest that the antifungal potential of diphenyl diselenide and ebselen deserves further investigation in in vivo experimental models, especially in combination with amphotericin B and voriconazole.

Antioxidant capacity, antimicrobial activity and triterpenes isolated from Jatropha isabellei Müll Arg.

Jatropha isabellei Müll Arg. belongs to the family Euphorbiaceae. The antioxidant capacity of this plant was evaluated by the DPPH method and inhibition of thiobarbituric acid reactive substances (TBARS). Ethyl acetate fraction demonstrated the best antioxidant capacity against the DPPH free radical and its profile was similar to ascorbic acid. This fraction also presented the best results of phenolics, flavonoids and condensed tannins, showing a positive relation between the phenolic content and antioxidant activity. All fractions and the crude extract were able to inhibit significantly the TBARS production induced by Fe(II) for the two tested concentrations, reaching the basal levels. In this test, ethyl acetate and dichloromethane fraction showed good values for inhibitory concentration. The dichloromethane fraction showed the best results against the fungi Sporothrix schenckii and Fusarium proliferatum and the bacterium of Micrococcus genus. This fraction allowed the isolation of acetil aleuritolic acid and a mixture of sitosterol 3-O-ß-D-glucoside and stigmasterol, described for the first time in this species.