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Drugs of Choice
This page summarizes primary and alternative drugs for the treatment of specific fungal infections. This page focuses on medical therapeutic approaches and it must be remembered that other therapeutic measures (most commonly, surgical excision and debridement) are required in combination with antifungal therapy for some fungal infections. Please refer to the related page about each fungal infection for additional data.
Please also see our discussion on cost analysis and pharmacoeconomic analysis of antifungal therapy.
The tables are presented in two sections. The first table shows drugs of choice and the second table shows suitable dosages. These abbreviations are used throughout the tables:
- AMB: Amphotericin B deoxycholate (Fungizone)
- ABLC: Amphotericin B lipid complex (Abelcet)
- ABCD: Amphotericin B colloidal dispersion (Amphotec)
- LAMB: Liposomal amphotericin B (AmBisome)
- Echinocandin: Caspofungin, micafungin or anidulafungin
The following table summarizes the therapeutic options in the more frequent systemic fungal infections [85, 99, 114, 291, 421, 525, 795, 946, 1000, 1001, 1003, 1168, 1406, 1623, 1737, 1915, 1934, 1993, 2163, 2290, 2415]. Some of the treatment modalities have not been formally approved by the US Food and Drug Administation.
| MYCOSES |
DRUG OF CHOICE |
ALTERNATIVE(S) |
| Aspergillosis |
Voriconazole |
Itraconazole |
| An AMB preparationa |
Echinocandin |
| Itraconazole (used in milder forms or after more severe disease is stabilized with an AMB preparation)a |
Posaconazole |
| Blastomycosis |
An AMB preparationa |
Ketoconazole |
| Itraconazole capsule (for mild to moderate disease) |
Fluconazole PO |
| Candidiasisb |
|
|
| Candidemia and invasive candidiasis |
Echinocandin
An AMB preparationa |
ABLC |
| Fluconazoleb IV or PO |
ABCD
LAMB |
| Oropharyngeal candidiasis |
Fluconazoleb PO |
Ketoconazole
Itraconazole
Clotrimazole troche
Nystatin oral suspension
AMB oral suspension
AMB IVc |
| Esophageal candidiasis |
Fluconazoleb PO |
Ketoconazole
Itraconazole
AMB IVc
Echinocandind |
| Vulvovaginal candidiasis |
Fluconazoleb, e PO single dose |
Ketoconazole |
| Topical azole preparations |
Itraconazole |
| Nystatin vaginal tablet |
Boric acid |
| Coccidioidomycosis |
An AMB |
Ketoconazole |
| preparationa (for rapidly progressive disease) |
Itraconazole
Voriconazole
Posaconazole |
| Fluconazole PO or IV (for subacute/chronic disease or coccidioidal meningitis) |
AMB intrathecalf |
| Cryptococcosis |
An AMB preparationa+Flucytosine |
LAMB
Voriconazole
Posaconazole |
| Chronic suppressive therapy with fluconazole PO in AIDS patients (lifelong) |
Itraconazole capsule
Chronic suppressive therapy with itraconazole capsule or AMB (weekly) in AIDS patients (lifelong) |
| Dermatophytosisg (other than dermatophytic onychomycosis) |
Terbinafine |
Griseofulvin |
| Itraconazole capsule |
Fluconazole Topical therapy |
| Histoplasmosis |
AMB (for severe disease) |
ABLC |
| Itraconazole (for mild to moderate disease) |
ABCD
LAMB
Ketoconazole
Fluconazole |
| Chronic suppressive therapy with itraconazole capsule in AIDS patients (lifelong) |
Chronic suppression therapy with itraconazole capsule, fluconazole PO or AMB (weekly) in AIDS patients (lifelong) |
| Onychomycosis |
|
|
| Candida onychomycosis |
Itraconazole capsule |
|
| Dermatophytic onychomycosis |
Terbinafine |
Griseofulvin |
| Itraconazole oral capsule |
Topical cicloprox olamine
Fluconazole |
| Paracoccidioidomycosis |
An AMB preparationa
Itraconazole (for mild to moderate disease) |
Ketoconazole |
| Pseudallescheriasis |
Voriconazole
Itraconazole
Ketoconazole
Posaconazole |
|
| Sporotrichosis |
|
|
| Cutaneous and lymphocutaneous sporotrichosis |
Itraconazole |
Potassium iodide
Fluconazole PO |
| Systemic sporotrichosis |
An AMB preparationa (for severe disease)
Itraconazole (for mild to moderate disease)
Chronic suppressive therapy with itraconazole capsule in AIDS patients (lifelong) |
Fluconazole PO |
| Zygomycosis |
An AMB preparationa |
Posaconazole |
a. The lipid formulations of amphotericin B are licensed for use in patients whose infection is intolerant or refractory to amphotericin B deoxycholate treatment. However, a lipid AMB (ABLC, ABCD, or LAMB) can generally be substituted and is often preferred for mould infections.
b. Fluconazole should not be used in any clinical form of candidiasis due to Candida krusei as this species is felt to be intrinsically resistant to fluconazole. For other Candida spp., such as Candida glabrata, in vitro antifungal susceptibility test results may be used to determine whether the infecting strain is susceptible to fluconazole. See our discussion of the usual susceptibility patterns of Candida spp.
c. Indicated only in azole-refractory or azole-resistant infections.
d. Caspofungin has activity here, but is not licensed for this indication. Limited safety data exist for caspofungin and the risk/benefit ratio for its use here would need to be carefully evaluated.
e. 150 mg single dose therapy.
f. May be indicated in patients who do not respond to fluconazole.
g. In patients with widespread skin lesions and tinea capitis, oral therapy is indicated since topical therapy frequently fails.
Below are the generally recommended doses of systemically administered antifungal agents. The optimal dose may need to be modified depending on the severity of the infection as well as the immune status of the host. Thus, the recommendations below are not strict and their use requires cautious individual evaluation of each patient.
| DRUG |
USUAL DOSE |
| AMB |
0.6-1.5 mg/kg/day IV (doses above 1 mg/kg/d tend to be highly nephrotoxic and must be administered with great caution)
10 µg intravitreal
Oral suspension
100 mg (1 ml) four times daily |
| ABCD |
3-4 mg/kg/day IV |
| ABLC |
5 mg/kg/day IV |
| LAMB |
3-6 mg/kg/day IV |
| Boric acid |
600 mg gelatin capsule once daily intravaginal |
Caspofungin
Micafungin
Anidulafungin |
Loading dose of 70 mg/day, followed by 50 mg/day IV
50-150 mg/day
Loading dose of 100-200 mg/day, followed by 50-100 mg/day
|
| Clotrimazole troche |
10 mg five times daily PO |
| Fluconazole |
100-800 mg once/bid PO
150 mg PO single dose therapy (for vulvovaginal candidiasis)
400-800 mg IV |
| Flucytosine |
25 mg/kg qid PO |
| Griseofulvin |
10-20 mg/kg/day PO tablet/syrup |
| Itraconazole |
200-400 mg capsule once/bid PO
Oral solution 200 mg (20 ml) once daily |
| Voriconazole |
6 mg/kg q12h day#1, the 3-4 mg/kg/q12h IV
200 mg qid PO |
| Posaconazole |
800 mg/day PO divided doses (bid-qid) |
| Ketoconazole |
400-800 mg once/bid PO |
| Nystatin |
500,000 U (5 ml) oral suspension four times daily PO
100,000 U vaginal tablet once daily |
| Potassium iodide (saturated solution) |
1-5 ml tid PO |
| Terbinafine |
250 mg/day PO |
|
|
References
85. Anonymous. 2000. Cicloprox (Penlac) nail lacquer for onychomycosis. The Medical Letter. 42:51.
99. Anonymous. 1997. Systemic Antifungal Drugs. The Medical Letter. 39:86-88.
114. Arenas, R., J. Dominguez-Cherit, and L. M. Fernandez. 1995. Open randomized comparison of itraconazole versus terbinafine in onychomycosis. Int. J. Dermatol. 34:138-43.
291. Boogaerts, M., and J. Maertens. 2001. Clinical experience with itraconazole in systemic fungal infections. Drugs. 61:39-47.
421. Chapman, S. W., R. W. Bradsher, G. D. Campbell, P. G. Pappas, and C. A. Kauffman. 2000. Practice guidelines for the management of patients with blastomycosis. Clin. Infect. Dis. 30:679-683.
525. de Doncker, P., A. K. Gupta, G. Marynissen, P. Stoffels, and A. Heremans. 1997. Itraconazole pulse therapy for onychomycosis and dermatomycoses: An overview. J. Am. Acad. Dermatol. 37:969-974.
795. Galgiani, J. N., N. M. Ampel, A. Catanzaro, R. H. Johnson, D. A. Stevens, and P. L. Williams. 2000. Practice guidelines for the treatment of coccidioidomycosis. Clin. Infect. Dis. 30:658-661.
946. Gupta, A. K., P. Fleckman, and R. Baran. 2000. Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis. J Amer Acad Dermatol. 43:S70-S80.
1000. Havu, V., H. Brandt, H. Heikkila, A. Hollmen, R. Oksman, T. Rantanen, S. Saari, S. Stubb, K. Turjanmaa, and T. Piepponen. 1997. A double-blind, randomized study comparing itraconazole pulse therapy with continuous dosing for the treatment of toe-nail onychomycosis. Br. J. Dermatol. 136:230-4.
1001. Havu, V., H. Heikkila, K. Kuokkanen, M. Nuutinen, T. Rantanen, S. Saari, S. Stubb, R. Suhonen, and K. Turjanmaa. 2000. A double-blind, randomized study to compare the efficacy and safety of terbinafine (Lamisil (R)) with fluconazole (Diflucan (R)) in the treatment of onychomycosis. Brit J Dermatol. 142:97-102.
1003. Hay, R. J. 2000. Dermatophytosis and other superficial mycoses, p. 2757-2768. In G. L. Mandell, J. E. Bennett, and R. Dolin (ed.), Mandell, Douglas & Bennett's Principles and Practice of Infectious Diseases, 5th ed. ed, vol. 2. Churchill Livingstone, London.
1168. Kauffman, C. A., R. Hajjeh, S. W. Chapman, and Mycoses Study Group. 2000. Practice guidelines for the management of patients with sporotrichosis. Clin. Infect. Dis. 30:684-687.
1406. Maertens, J., I. Raad, C. A. Sable, A. Ngai, R. Berman, T. F. Patterson, D. Denning, and T. Walsh. 2000. Multicenter, noncomparative study to evaluate safety and efficacy of caspofungin in adults with aspergillosis refractory or intolerant to amphotericin B, amphotericin B lipid formulations, or azoles. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract No. 1103.
1623. National Committee for Clinical Laboratory Standards. 1997. Reference method for broth dilution antifungal susceptibility testing of yeasts; Approved standard NCCLS document M27-A. National Committee for Clinical Laboratory Standards, Wayne, Pa.
1737. Patterson, T. F., W. R. Kirkpatrick, M. White, J. W. Hiemenz, J. R. Wingard, B. Dupont, M. G. Rinaldi, D. A. Stevens, and J. R. Graybill. 2000. Invasive aspergillosis - Disease spectrum, treatment practices, and outcomes. Medicine. 79:250-260.
1915. Rex, J. H., T. J. Walsh, J. D. Sobel, S. G. Filler, P. G. Pappas, W. E. Dismukes, and J. E. Edwards. 2000. Practice guidelines for the treatment of candidiasis. Clin. Infect. Dis. 30:662-678.
1934. Roberts, D. T. 1994. Oral therapeutic agents in fungal nail disease. J. Amer. Acad. Dermatol. 31:S78-81.
1993. Saag, M. S., R. J. Graybill, R. A. Larsen, P. G. Pappas, J. R. Perfect, W. G. Powderly, J. D. Sobel, W. E. Dismukes, and the Mycoses Study Group Cryptococcal Subproject. 2000. Practice guidelines for the management of cryptococcal disease. Clin. Infect. Dis. 30:710-718.
2163. Stevens, D. A., V. L. Kan, M. A. Judson, V. A. Morrison, S. Dummer, D. W. Denning, J. E. Bennett, T. J. Walsh, T. F. Patterson, and G. A. Pankey. 2000. Practice guidelines for diseases caused by Aspergillus. Clin. Infect. Dis. 30:696-709.
2290. van Gool, R. 2001. The cost of treating systemic fungal infections. Drugs. 61:49-56.
2415. Wheat, J., G. Sarosi, D. McKinsey, R. Hamill, R. Bradsher, P. Johnson, J. Loyd, and C. Kauffman. 2000. Practice guidelines for the management of patients with histoplasmosis. Clin. Infect. Dis. 30:688-695.
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