Luana Rossato

Synergysm of voriconazole or itraconazole with other antifungal agents against species of Fusarium.

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

Fusarium 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.

In vitro interaction of antifungal and antibacterial drugs against Cryptococcus neoformans var. grubii before and after capsular induction

This study evaluated the synergistic interactions between amphotericin B (AMB) and azithromycin (AZM), daptomycin (DAP), linezolid (LNZ), minocycline (MINO), fluconazole (FLZ), flucytosine (5FC), linezolid (LZD), or tigecycline (TIG) against clinical isolates of Cryptococcus neoformans var. grubii before and after capsule induction. High synergism (>75%) was observed for the combinations, AMB+5FC, AMB+TIG, AMB+AZM, AMB+LZD and AMB+MINO but only in the strains after capsule induction. The results show that the presence of the capsule may lower the minimum inhibitory concentrations (MICs) of antifungal agents, but antimicrobial activity can be improved by combining antifungal and antibacterial agents.

INFECÇÕES CAUSADAS POR MALASSEZIA: NOVAS ABORDAGENS

O genero Malassezia compreende fungos leveduriformes lipofilicos e lipodependentes que recentemente sofreram mudancas em sua classificacao taxonomica, com a introducao de quatro novas especies: M. globosa, M. obtusa, M. slooffiae e M. restricta, alem das especies M. furfur, M. pachydermatis e M. sympodialis, anteriormente descritas. Estes fungos estao associados a varios quadros patologicos que incluem infeccoes como a pitiriase versicolor, dermatite seborreica, dermatite atopica, fungemia, entre outros. Estes quadros eram, ate pouco tempo atras, considerados exclusivamente causados pela especie M. furfur. As mudancas na classificacao taxonomica do genero Malassezia levaram a uma reavaliacao dos procedimentos laboratoriais utilizados para a identificacao deste agente etiologico. Entre eles podemos citar o estudo e a caracterizacao morfologica das especies, sua tolerância termica, suas necessidades nutricionais para determinados tipos de acidos graxos, bem como a composicao e as caracteristicas do DNA de cada uma delas.

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.