J Clin Med Res

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

Journal website http://www.jocmr.org

Review

Volume 9, Number 6, June 2017, pages 451-456

Combination Antifungal Therapy: A Review of Current Data

Tables

**Table 1.** Suggested Mechanisms of Synergism and Antagonism [14-19, 24-26]
Combination of antifungals	Synergism (S) or antagonism (A)	Mechanism	Reference
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 + azole	S	Inhibition of ergosterol biosynthesis	Barchiesi 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 + flucytosine	S	Cell wall damage (AmB or azole) and increase uptake of flucytosine	Yamamoto et al [18] (pulmonary cryptococcosis) Polak [19] (septicemic candidiasis)
AmB + azole	A	Modification 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 + flucytosine	A	Changing of the cell membrane function	Shadomy 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 candidiasis	AmB + flucytosine	Pappas et al [10], 2016 IDSA guidelines*
	AmB + azole	Rex et al [33]
	Echinocandin + azole	Cui et al [34] Chen et al [35]
Invasive aspergillosis	Azole or AmB + echinocandin	Patterson et al [9], 2016 IDSA guidelines **Panackal et al [41]
Invasive aspergillosis	Voriconazole + anidulafungin	Marr et al [43]
Mucormycosis	AmB + posaconazole or caspofungin	Cornely et al [11]***