Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc
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Volume 9, Number 6, June 2017, pages 451-456

Combination Antifungal Therapy: A Review of Current Data


Table 1. Suggested Mechanisms of Synergism and Antagonism [14-19, 24-26]
Combination of antifungalsSynergism (S) or antagonism (A)MechanismReference
Note that AmB combined with flucytosine had been reported to have synergy both in vitro and in vivo, but in some in vitro studies, partial antagonism was reported. This aspect of the interaction of Amphotericin and flucytosine is still not well clarified.
Terbinafine + azoleSInhibition of ergosterol biosynthesisBarchiesi et al [14] (C. albicans)
Guerra et al [15] (C. neoformans)
Ashley and Johnson [16] (Dermatophytes)
Perea et al [17] (C. glabrata)
AmB or azole + flucytosineSCell wall damage (AmB or azole) and increase uptake of flucytosineYamamoto et al [18] (pulmonary cryptococcosis)
Polak [19] (septicemic candidiasis)
AmB + azoleAModification of a target in the fungal cell (prevention of ergosterol synthesis by the azole)Sugar and Liu [24] (invasive candidiasis)
Baddley et al [26] (invasive candidiasis)
AmB + flucytosineAChanging of the cell membrane functionShadomy et al [25] (C. neoformans and C. tropicalis)


Table 2. Commonly Used CAF Therapy [9-11, 33-35, 41, 43]
Commonly used CAF therapy
*Amphotericin B with or without flucytosine for initial therapy for candida native valve endocarditis, candida CNS infection, azole-resistant Candida glabrata, ascending pyelonephritis and fluconazole-resistant candida endophthalmitis. **Salvage therapy with echinocandin either alone or in combination against invasive aspergillosis. Uncertainty of the CAF still exists. ***Intent to cure therapy for refractory disease or in case of intolerance to prior antifungal therapy.
Invasive candidiasisAmB + flucytosinePappas et al [10], 2016 IDSA guidelines*
AmB + azoleRex et al [33]
Echinocandin + azoleCui et al [34]
Chen et al [35]
Invasive aspergillosisAzole or AmB + echinocandinPatterson et al [9], 2016 IDSA guidelines
**Panackal et al [41]
Voriconazole + anidulafunginMarr et al [43]
MucormycosisAmB + posaconazole or caspofunginCornely et al [11]***