South American Blastomycosis Medication

Antifungal medications are the mainstay of treatment for South American blastomycosis. Most conditions respond well to these agents. Itraconazole, ketoconazole, fluconazole, amphotericin B, trimethoprim and sulfamethoxazole (TMP-SMZ), and sulfadiazine have all been successfully used to treat South American blastomycosis.^[16] Itraconazole and ketoconazole have become the drugs of choice in treatment; itraconazole is generally considered the superior of the two.^{[17, 18]}

Historically, the sulfonamides have been the most widely used medications for the treatment of P braziliensis; their advantage is their low cost. However, relapses are more common with the sulfonamides than with other mediations, and longer courses of therapy are required. The percentage of patients who have a relapse after receiving sulfonamides is 20-30%, whereas with itraconazole it is 3.5-10% and with ketoconazole it is 7-11%. Further, 3-5 years of sulfonamide therapy may be required, whereas 6-10 months and 6-12 months are recommended with itraconazole and ketoconazole, respectively.

Fluconazole is not as effective as either itraconazole or ketoconazole. Its main advantages are that it is available in both oral and intravenous forms and that it penetrates into the cerebrospinal fluid (CSF) well.

Amphotericin B is used in patients with severe disease who cannot tolerate oral medications. It generally is given for 4-8 weeks and followed by sulfonamides for 2-3 years. Because of its high rate of adverse reactions and low patient tolerance, its use is reserved for the most ill patients. Its low cost is an advantage in Central America and South America. Amphotericin B is the only medication in this list in pregnancy category B; all the other medications are pregnancy category C or D.

At this time, sulfadiazine and TMP-SMZ are still used for South American blastomycosis because of their low cost.

Reports have documented successful treatment with voriconazole, posaconazole, and terbinafine.^[19]

These guidelines may be helpful: Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America.

Class Summary

The mechanism of action may involve an alteration of RNA or DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Itraconazole (Sporanox)

Considered DOC. Triazole antifungal agent that blocks the synthesis of ergosterol, an integral component of the fungal cell membrane.

IV formulation now available but no IV dose established for P brasiliensis treatment.

Ketoconazole (Nizoral)

Fungistatic activity. Imidazole broad-spectrum antifungal agent; inhibits synthesis of ergosterol, causing cellular components to leak and result in fungal cell death.

Fluconazole (Diflucan)

Fungistatic activity. Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. Not considered DOC in the treatment of South American blastomycosis.

Amphotericin B (Amphocin, Fungizone)

Antifungal agent that binds to sterols in fungal cell membrane. Binding changes membrane permeability, which results in intracellular components to leak out of fungal cells. Indicated for the treatment of life-threatening fungal infections or when oral antifungal medications cannot be tolerated.

Terbinafine (Lamisil)

Fungicidal activity. Inhibits squalene epoxidase, which decreases ergosterol synthesis, causing fungal cell death. Clinical experience with terbinafine is limited in the treatment of South American blastomycosis.

Voriconazole (Vfend)

A triazole antifungal agent that inhibits fungal cytochrome P450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.

Posaconazole (Noxafil)

Triazole antifungal agent. Blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation, which results in cell membrane disruption. Available as oral susp (200 mg/5 mL). Indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Trimethoprim and sulfamethoxazole (Septra, Bactrim)

Sulfamethoxazole competes with para-aminobenzoic acid (PABA) and thereby inhibits microbial synthesis of dihydrofolate. Trimethoprim binds to and reversibly inhibits the enzyme dihydrofolate reductase, thereby blocking the production of tetrahydrofolic acid from dihydrofolic acid. Thus, 2 consecutive steps in the synthesis of essential nucleic acids and proteins are blocked. Used to treat South American blastomycosis in Central America and South America primarily because of its low cost. Not DOC.

Sulfadiazine (Microsulfon)

Sulfonamide antimicrobial agent that exerts bacteriostatic action through competitive antagonism with PABA.

Microorganisms that require exogenous folic acid and do not synthesize folic acid are not susceptible to the action of sulfonamides. Used for the treatment of South American blastomycosis in Central America and South America primarily because of its low cost. Not DOC.