Antifungal Activity In Combination Research Articles

Recurrent Dermatophytosis: A Comparative Therapeutic Study using Oral Itraconazole Alone and in combination with Topical Tincture of Iodine

Widespread resistant dermatophytosis cases have been increasing in frequency in Iraq, despite prolonged treatment protocol. This study aimed to compare the therapeutic effect of oral itraconazole alone and in combination with topical tincture of iodine as an adjuvant therapy for refractory dermatophytosis. A comparative research was conducted in the Dermatology and Venereology Department, Ramadi Teaching Hospital. A total number of 130 cases with recurrent tenia were enrolled in this study. All patients were diagnosed on clinical basis and direct microscopic examination. They divided into two groups depending on the line of treatment. Only 120 patients completed the study, 82(68.3%) were males, and 38(31.7%) were female. The age ranged (18-60 years) with mean (± SD) 33.3+12.7. Marked improvement and clinical cure at 2 weeks were highly significant level in 44(75.9%) cases of those treated by 5% topical tincture of iodine plus oral itraconazole, VS 14(24.1%) of individual treated by only oral itraconazole. While there was no significant difference in cure rate between both groups at 12 weeks follow up. Topical 5% iodine tincture is recommended as a synergistic antifungal activity in combination with oral itraconazole in treatment of recurrent tinea infections.

Improved efficacy of antifungal drugs in combination with monoterpene phenols against Candida auris

Emergence of Candida auris has been described as a global health threat due to its ability to cause invasive infections with high mortality rate and multidrug resistance. Novel drugs and therapies are required to target this organism and its pathogenicity. Anti-virulence approach and combination therapy have been proposed as alternatives in recent years. This study evaluated the virulence factors in C. auris, combination antifungal activity of phenolic compounds with antifungal drugs and determined effect of the most active compound on positive pathogenicity markers of C. auris. Antifungal susceptibility profile of 25 clinical isolates of C. auris against antifungal agents as well as against phenolic compounds was obtained using CLSI guidelines. Combination of the most active phenolic compound with antifungal drugs was determined. Effect of carvacrol on the virulence factors was also studied. Carvacrol was the most active phenol with median MIC of 125 µg/ml and its combination with fluconazole, amphotericin B, nystatin and caspofungin resulted synergistic and additive effects in 68%, 64%, 96% and 28%, respectively. Combination also reduced the MIC values of the drugs. All test strains showed adherence ability to epithelial cells and 96% of strains produced proteinase. None of the strains produced hyphae and phospholipase. At low concentrations, carvacrol significantly inhibited the adherence ability and proteinase production (both p < 0.01). Carvacrol has antifungal and anti-virulence activity against C. auris. It also showed an enhanced antifungal activity in combination with antifungal agents. Therefore it has potential to be developed into a novel antifungal agent.

Synergistic antimicrobial activity of Boswellia serrata Roxb. ex Colebr. (Burseraceae) essential oil with various azoles against pathogens associated with skin, scalp and nail infections.

Eradication of skin and nail infections still remain a challenge and there are serious concerns regarding the recurrence of the diseases associated with these infections. Antimicrobials from plant sources are gaining importance in therapeutics because they encounter minimal challenges of emergence of resistance. We have demonstrated the antimicrobial activity of Boswellia serrata essential oil against micro-organisms involved in skin, scalp and nail infections, especially if it has shown favourable synergistic antifungal activity in combination with azoles against the azole-resistant Candida albicans strain. Thus, B.serrata oil can be one of the plausible therapeutic agents for management of skin, scalp and nail infections.

Novel carboline derivatives as potent antifungal lead compounds: design, synthesis, and biological evaluation.

A series of novel antifungal carboline derivatives was designed and synthesized, which showed broad-spectrum antifungal activity. Particularly, compound C38 showed comparable in vitro antifungal activity to fluconazole without toxicity to human embryonic lung cells. It also exhibited good fungicidal activity against both fluconazole-sensitive and -resistant Candida albicans cells and had potent inhibition activity against Candida albicans biofilm formation and hyphal growth. Moreover, C38 showed good synergistic antifungal activity in combination with fluconazole (FLC) against FLC-resistant Candida species. Preliminary mechanism studies revealed that C38 might act by inhibiting the synthesis of fungal cell wall.

Activity of antifungal combinations against Aspergillus species evaluated by isothermal microcalorimetry

We evaluated the activity of antifungals alone or in combination against Aspergillus fumigatus and Aspergillus terreus by real-time measurement of fungal growth-related heat production. Amphotericin B, voriconazole, caspofungin, and anidulafungin were tested alone or in combination. Heat production was measured in Sabouraud dextrose broth containing 105Aspergillus conidia/mL for 48 h at 37 °C. Antifungal activity was evaluated by measuring the heat detection time relative to the growth control. Against A. fumigatus, the voriconazole-echinocandin combination demonstrated longer heat detection time than each antifungal alone. Against A. terreus, the combination amphotericin B–echinocandin prolonged the heat detection time, compared to each antifungal alone. In contrast, the echinocandin-voriconazole combination did not increase the heat detection time, compared to voriconazole alone. None of the antifungal combinations decreased the heat detection time compared to the antifungals alone (e.g. antagonism was not observed). Microcalorimetry has the potential for real-time evaluation of antifungal combinations against Aspergillus spp.

In vitro antifungal activity of the berberine and its synergism with fluconazole

Berberine with and without fluconazole was tested by an agar disk diffusion assay in which clinical isolates of Candida albicans were applied onto yeast extract-peptone-dextrose agar plate. Berberine, which had no intrinsic antifungal activity at the concentration tested, exerted a powerful antifungal activity in combination of fluzonazole. Combinations of berberine and fluconazole were also tested by the checkerboard assay to determine whether they had favorable or unfavorable antifungal interactions. The MIC of fluconazole was 1.9 microg/ml when the drug was tested alone and decreased to 0.48 microg/ml in the presence of berberine concentrations of 1.9 microg/ml. However, berberine at concentrations of >1.9 microg/ml combined with a fluconazole supra-MIC (i.e., >1.9 microg/ml) eliminated the residual turbidity in the incubation wells. This endpoint fitted to the definition of MIC-0 (optically clear wells) and reflected the absence of a trailing effect, which is the result of a residual growth at fluconazole concentrations greater than the MIC.

Deoxycholate amphotericin B and amphotericin B lipid complex exert additive antifungal activity in combination with pulmonary alveolar macrophages against Fusarium solani

Fusarium spp. have emerged as important causes of invasive fungal infections in immunocompromised patients. Rabbit pulmonary alveolar macrophages (PAMs) exhibited fungicidal activity against conidia of Fusarium solani and achieved a time-dependent increase in killing. Neither deoxycholate amphotericin B (DAMB) nor amphotericin B lipid complex (ABLC) exerted a suppressive effect on PAMs by decreasing their conidiocidal activity against F. solani. On the contrary, at a concentration of 0.125 microg ml(-1), ABLC and, to a lesser degree, DAMB additively augmented the fungicidal activity of pulmonary alveolar macrophages against conidia of Fusarium solani.

Amphotericin B lipid complex exerts additive antifungal activity in combination with polymorphonuclear leucocytes against Scedosporium prolificans and Scedosporium apiospermum.

Scedosporium prolificans and Scedosporium apiospermum are resistant to most antifungal agents and cause refractory pulmonary and disseminated infections. The combined effects of deoxycholate amphotericin B, amphotericin B lipid complex and liposomal amphotericin B with human polymorphonuclear leucocytes (PMNs) in damaging hyphae of these fungi were evaluated by XTT assay. Amphotericin B lipid complex displayed a significant additive effect with PMNs against both Scedosporium species (22% for S. prolificans and 81% for S. apiospermum; P < 0.04). None of the formulations adversely affected the PMN antifungal activity. These findings may be important in designing better strategies for management of infections due to these organisms.

Amphotericin B formulations exert additive antifungal activity in combination with pulmonary alveolar macrophages and polymorphonuclear leukocytes against Aspergillus fumigatus.

Deoxycholate amphotericin B (DAMB) and amphotericin B lipid complex (ABLC) additively augmented the fungicidal activity of pulmonary alveolar macrophages against the conidia of Aspergillus fumigatus. DAMB, ABLC, and liposomal amphotericin B similarly displayed additive effects with polymorphonuclear leukocytes in damaging the hyphal elements of A. fumigatus.

Endochitinase fromGliocladium virens: Isolation, Characterization, and Synergistic Antifungal Activity in Combination with Gliotoxin

The culture filtrate from the biocontrol agent Gliocladium virens strain 41 grown in chitin-containing medium was strongly inhibitory to mycelial growth of different plant-pathogenic fungi. The antibiotic gliotoxin was isolated from the culture liquid. The culture filtrate also contained different types of chitinolytic enzyme activities, including endochitinase, chitin 1,4β-chitobiosidase, and glucan N-acetyl-β-D-glucosaminidase, as well as glucan 1,3-β-glucosidase activity. An endochitinase was purified to homogeneity []