Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans

Figures & data

Table 1. ^*Selected synergistic combinations against C. albicans in vitro and in vivo.

Data from	Wild type or resistance^#	Synergistic combination	Reference
In vitro Animal	Wild type and Resistance	Beauvericin + Clotrimazole, or Fluconazole, or Itraconazole, or Ketoconazole, or Miconazole	Unpublished
In vitro	Wild type and Resistance	Rapamycin + peptides	Unpublished
In vitro	Wild type and Resistance	Ketoconazole + Avilamycin	Unpublished
In vitro	Wild type and Resistance	Ketoconazole + Spinosad	Unpublished
In vitro	Wild type and Resistance	Nitroimidazoles + Amphotericin B	^Citation83
In vitro	Wild type and Resistance	Histatin 5 and its analogs Amphotericin B	^Citation84
In vitro	Wild type and Resistance	Tetrandrine + Ketoconazole	^Citation85
In vitro	Wild type and Resistance	Fluconazole + Thymol, or Carvacrol	^Citation86
In vitro	Wild type and Resistance	Geldanamycin + Fluconazole	^Citation87
In vitro	Wild type and Resistance	Pure polyphenol curcumin I + Fluconazole, or Miconazole, or Ketoconazole, or Itraconazole, or Voriconazole, or Nystatin or Amphotericin B	^Citation88
In vitro	Wild type and Resistance	Berberine + Fluconazole	^Citation89-91
In vitro	Wild type and Resistance	Fluconazole + alverine citrate, or Caspofungin, Latrunculin-A, or Wortmannin, or Fenpropimorph	^Citation92
In vitro	Wild type and Resistance	Tunicamycin + FK506, or Cyclosporine-A	^Citation92
In vitro	Wild type and Resistance	Wortmannin + Tunicamycin, or FK506	^Citation92
In vitro	Wild type and Resistance	Posaconazole + Caspofungin, or FK506	^Citation93
In vitro	Wild type and resistance	Amphotericin B + Terbinafine	^Citation94
In vitro	Wild type and Resistance	Flucytosine + Econazole, or Miconazole	^Citation95
In vitro	Wild type and Resistance	Fluvastatin + Fluconazole, or Itraconazole	^Citation96
In vitro	Wild type and Resistance	FK506 + Fluconazole, or Voriconazole, or Itraconazole	^Citation97
In vitro	Wild type and Resistance	Retigeric acid B + Fluconazole, or Ketoconazole, or Itraconazole	^Citation98
In vitro	Wild type and Resistance	Lactoferrin + Fluconazole, or Itraconazole	^Citation99
In vitro	Wild type and Resistance	Farnesol + Fluconazole, or Ketoconazole, or Miconazole, or Amphotericin B	^Citation100
In vitro	Wild type and Resistance	Amiodarone + Fluconazole, or Voriconazole, or Itraconazole	^Citation101
In vitro	Resistance	Eugenol + Amphotericin B, or Fluconazole	^Citation102
In vitro	Resistance	Honokiol + Fluconazole	^Citation103
In vitro	Resistance	Glabridin + Fluconazole	^Citation104
In vitro	Resistance	Tioconazole + Butylated hydroxyanisole	^Citation105
In vitro	Resistance	Baicalein + Amphotericin B	^Citation106
In vitro	Resistance	Curcumin+ R6G, or Ketoconazole, or Itraconazole, or Miconazole	^Citation107
In vitro	Resistance	Anidulafungin + Posaconazole, or Amphotericin B	^Citation108
In vitro	Resistance	Caspofungin + Posaconazole, or Micafungin	^Citation108
In vitro	Resistance	Minocycline + Fluconazole	^Citation109
In vitro	Resistance	Baicalein + Fluconazole	^Citation110
In vitro	Resistance	Ofloxacin + Fluconazole	^Citation111
In vitro	Biofilm and Planktonic cells	Fluconazole + FK506, or Cyclosporine A	^Citation112
In vitro	Biofilm and Planktonic cells	Berberine + Miconazole	^Citation113
In vitro	Biofilm and Planktonic cells	Aspirin + Amphotericin B	^Citation114
In vitro	Biofilm	Tyrocidines + Amphotericin B, or Caspofungin	^Citation115
In vitro	Biofilm	Amphotericin B + Drospirenone, or Perhexiline, or Toremifene	^Citation116
In vitro	Biofilm	Caspofungin + Drospirenone, or Perhexiline, or Toremifene	^Citation116
In vitro	Biofilm	Amphotericin B + N-acetylcysteine, or EDTA, or Ethanol, or Talactoferrin	^Citation117
In vitro	Biofilm	Fluconazole + N-acetylcysteine, or EDTA, or Ethanol, or Talactoferrin	^Citation117
In vitro	Biofilm	Terpenes + Fluconazole	^Citation118
In vitro	Biofilm	Doxycycline + Fluconazole	^Citation119
In vitro	Biofilm	Silver nanoparticles + nystatin, or chlorhexidine digluconate	^Citation120
In vitro	Biofilm	Doxycycline + Fluconazole	^Citation121
In vitro	Biofilm	Shearinines D (3) and E (4) + Amphotericin B	^Citation122
In vitro	Biofilm	Verapamil + Fluconazole, or Tunicamycin	^Citation123
In vitro	Biofilm	Cyclosporine A + Fluconazole, or Voriconazole, or Amphotericin B, or Caspofungin	^Citation124
In vitro	Biofilm	Amphotericin B + Rifampicin, or Clarithromycin	^Citation125
Animal	Wild type and resistance	Posaconazole + Caspofungin, or FK506	^Citation126
Animal	Resistance	Amphotericin B + Caspofungin	^Citation127
Animal	Resistance	Tetrandrine + Ketoconazole	^Citation128
Animal	Wild type	Berberine + Amphotericin B	^Citation129
Animal	Wild type	Cilofungin + Amphotericin B	^Citation130
Animal	Wild type	Antimicrobial peptides + Caspofungin	^Citation131
Animal	Wild type	Nikkomycin Z + R 3783	^Citation132
Animal	Wild type	Amphotericin B + Ketoconazole, or 5-Fluorocytosine	^Citation133
Animal	Wild type	5-Fluorocytosine + Fluconazole, or Itraconazole	^Citation133
Animal	Biofilm	Fluconazole + FK506, or Cyclosporine A	^Citation112
Clinic trials	Clinical	Amphotericin B + 5-Fluorocytosine	^Citation134-137
Clinic trials	Clinical	5-Fluorocytosine + Azoles	^Citation138
Clinic trials	Clinical	Amphotericin B + Azoles	^Citation139
Clinic trials	Clinical	Terbinafine + Itraconazole or Fluconazole	^Citation140
Clinic trials	Clinical	Mycograb + lipid-associated amphotericin B	^Citation141

^* Because strains, culture conditions, susceptibility testing methods and models used to define synergy in these studies were different, results from different literatures may be contrary to each other, only synergy reports were selected in this table.

^# Strains were labeled as wild type if they were not claimed as resistance explicitly in the reference. For clinical trials, the infection sources are not distinguished, all labeled as clinical.

Figure 1. Antifungal drug targets and related drug resistant mechanisms of C. albicans Antifungal drugs and their targets: (A) polyenes, target is ergosterol; (B) azoles, target is ergosterol biosynthesis; (C) echinocandins, target is β(1 3)-D-glucan synthesis; (D) fluoropyrimidine, target is nucleic acids synthesis; (E) sordarins, target is protein synthesis; (F) griseofulvin, target is mitosis; (G) and arylamidines, target is mitochondria. The general drug resistant mechanisms in C. albicans include: 1. target overexpression; 2. targets alteration; 3. drug sequestration; 4. enhanced drug efflux; and 5. blocking of antifungal drug entry.

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