In vitro synergisms obtained by amphotericin B and voriconazole associated with non-antifungal agents against Fusarium spp

AbstractFusarium spp is an opportunistic fungal pathogen responsible for causing invasive hyalohyphomycosis in immunocompromised patients. Due to its susceptibility pattern with a remarkable resistance to antifungal agents the treatment failures and mortality rates are high. To overcome this situation, combination therapy may be considered which must be subjected to in vitro tests.In vitro activities of amphotericin B, itraconazole, and voriconazole associated with azithromycin, ciprofloxacin, fluvastatin, ibuprofen, metronidazole, and also the combination of amphotericin B plus rifampin against 23 strains of Fusarium spp. through the checkerboard technique based on M38-A2 [Clinical and Laboratory Standards Institute (2008). Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard, 2nd ed. (CLSI document M38-A2) (ISBN 1-56238-668-9). Wayne, PA: CLSI] were evaluated.The best synergistic interactions with amphotericin B were with ibuprofen (43.5%) (FICI [fractional inhibitory concentration index] range = 0.25–2). Combinations with voriconazole showed synergism, mainly with ciprofloxacin (30.4%) (FICI range = 0.25–3) and metronidazole (30.4%) (FICI range = 0.1–4); however, all the combinations with itraconazole were indifferent. In general, antagonistic interactions were not registered.Our results showed that in vitro synergisms obtained by some combinations studied deserve attention since they were better than those showed by the antimycotic

Revista Iberoamericana de Micología Synergysm of voriconazole or itraconazole with other antifungal agents against species of Fusarium

a b s t r a c t Background: Infections caused by Fusarium are difficult to treat because these fungi show in vitro and in vivo resistance to practically all the antifungal agents available, which explains the high mortality rates. An attempt to overcome fungal resistance is the combination of antifungal agents, especially those with different mechanisms of action. Aims: Evaluate the in vitro interactions of combinations of voriconazole or itraconazole with other antifungal agents against 32 isolates of Fusarium spp.: Fusarium chlamydosporum, Fusarium oxysporum, Fusarium proliferatum and Fusarium solani. Methods: Drug interactions were assessed by a checkerboard microdilution method that also included the determination of the MIC of each drug alone according to CLSI (Clinical and Laboratory Standards Institute) document M38-A2, 2008. Results: The best combinations were voriconazole + terbinafine which showed synergism against 84% of Fusarium strains. Other synergistic combinations were voriconazole + itraconazole (50%), voriconazole + fluconazole (50%), voriconazole + miconazole (38%), voriconazole + flucytosine (22%) and voriconazole + ketoconazole (25%). The synergisms observed with itraconazole combinations were: itraconazole + terbinafine (25%) and itraconazole + flucytosine (9.37%). The antagonisms observed were: voriconazole + fluconazole (3%) and itraconazole + flucytosine (12.5%). Conclusions: The synergism showed by voriconazole + terbinafine was remarkable. To better elucidate the potential usefulness of our findings, new in vivo and in vitro studies deserve be performed

In Vitro Activity of Terbinafine Combined with Caspofungin and Azoles against Pythium insidiosum▿

In this text we evaluated the in vitro antifungal activities of terbinafine combined with caspofungin, miconazole, ketoconazole, and fluconazole against 17 Pythium insidiosum strains by using the microdilution checkerboard method. Synergistic interactions were observed with terbinafine combined with caspofungin (41.2% of the strains), fluconazole (41.2%), ketoconazole (29.4%), and miconazole (11.8%). No antagonistic effects were observed. The combination of terbinafine plus caspofungin or terbinafine plus fluconazole may have significant therapeutic potential for treatment of pythiosis