Abstract:

The lack of an ideal antifungal drug or completely successful agent, suggests that combination therapy may be an appropriate option for the management of fungal infections. In this review, different antifungal combination therapy approaches will be discussed. In brief, the rationale for combination therapy is to maximize antifungal effects by attacking different fungal targets at the same time. However, the scientific basis for this approach requires evidence from prospective clinical trials of antifungal combinations. It is possible that real advantages will be seen for particular combinations only in particular mycoses and/or particular types of patient. Combination tends to reduce clinical failure when resistant strains could be recovered from patients, although drug interactions and cross-resistance may result. Synergy has been established between conventional antifungal agents and also between investigational molecules. Alternatively, combination of fluconazole and cyclosporine results fungicidal for fluconazole-susceptible strains of Candida albicans. An overall enhanced susceptibility is reached in intrinsically resistant Candida when combination of azole antifungal drugs or terbinafine with calcineurin inhibitors is used. Azoles, such as voriconazole, itraconazole, and fluconazole are being tested in combination with other antifungal agents such as amphotericin B, caspofungin, or terbinafine and. In addition, amphotericin B is actually administered in combined therapy with caspofungin. The traditional combinations of amphotericin B plus 5-fluorocytosine or amphotericin B plus rifampicin have been replaced by these newer combinations. Other combinations such as caspofungin plus amphotericin B or voriconazole have also been synergic against clinical isolates of Aspergillus and Fusarium. This has been confirmed in animal models in the case of caspofungin plus itraconazole in the treatment of invasive pulmonary aspergillosis and caspofungin plus liposomal amphotericin B in the management of invasive aspergillosis.

Author affiliation: Carrillo Muñoz, A. J.. Departamento de Micología; España

Author affiliation: Finquelievich, Jorge. Universidad de Buenos Aires. Facultad de Medicina; Argentina

Author affiliation: Tur Tur, Cristina. Departamento de Micología; España

Author affiliation: Eraso, Elena. Universidad del Pais Vasco; España

Author affiliation: Jaureguizar, Nerea. Universidad del Pais Vasco; España

Author affiliation: Quindós, Guillermo. Universidad del Pais Vasco; España

Author affiliation: Giusiano, Gustavo Emilio. Universidad Nacional del Nordeste. Instituto de Medicina Regional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Abstract:

Se ha estudiado el perfil de actividad antifúngica in vitrode amorolfina (AMR), bifonazol (BFZ), clotrimazol (CLZ), econazol(ECZ), fluconazol (FNZ), itraconazol (ITZ), ketoconazol(KTZ), miconazol (MNZ), oxiconazol (OXZ), tioconazol (TCZ) yterbinafina (TRB) frente a 26 aislamientos clínicos de Scopulariopsisbrevicaulis obtenidos de muestras clínicas de pacientescon onicomicosis, por medio de un método estandarizado demicrodilución. A pesar de que este hongo filamentoso ha sidodescrito como resistente frente a un amplio espectro de antifúngicos,los datos obtenidos muestran una mejor actividadfungistática in vitro de AMR, OXZ y TRB (0,08; 0,3 y 0,35 mg/L,respectivamente) en comparación con la de CLZ (0,47 mg/L),ECZ (1,48 mg/L), MNZ (1,56 mg/L, BFZ (2,8 mg/L), TCZ (3,33mg/L), KTZ (3,73 mg/L). FNZ (178,47 mg/L) e ITZ (4,7 mg/L) mostraronuna reducida actividad antifúngica in vitro. Las CMIs obtenidasmuestran la reducida sensibilidad in vitro en general deS. brevicaulis a los antifúngicos utilizados y que son de posibleuso para el tratamiento de las onicomicosis con la excepción deAMR, OXZ y TRB.

Author affiliation: Carrillo Muñoz, Alfonso Javier. ACIAM; España

Author affiliation: Tur Tur, Cristina. Cap Manso; España

Author affiliation: Cárdenes, Délia. ACIAM; España

Author affiliation: Rojas, Florencia Dinorah. Universidad Nacional del Nordeste. Instituto de Medicina Regional; Argentina

Author affiliation: Giusiano, Gustavo Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Nordeste. Instituto de Medicina Regional; Argentina