Medication Summary
Always consult the latest information regarding the drugs of choice (DOCs), the dosages, and the routes of administration. Consultation with infectious diseases specialists can be helpful in choosing appropriate therapy.
Antifungal agents
Class Summary
Systemic antifungal treatment is indicated for severe acute pulmonary histoplasmosis, chronic pulmonary histoplasmosis (CPH), progressive disseminated histoplasmosis (PDH), and any manifestation in an immunocompromised patient (see Treatment).
Amphotericin B is the mainstay of therapy for most systemic fungal infections. It is highly effective but has potential adverse effects. New lipid formulations of amphotericin B reduce renal toxicity; however, they are expensive and their improvements in efficacy are not proven. A double-blind randomized trial performed to compare liposomal amphotericin B (L-AMB) with the standard formulation (AmB) in patients with AIDS showed that L-AMB was at least as effective as AmB, with marked reduction in renal toxicity. [21]
Echinocandins (eg, caspofungin) should not be used.
Amphotericin B (Amphocin, Fungizone)
Produced by strain of Streptomyces nodosus. Fungistatic or fungicidal. Binds to sterols (eg, ergosterol) in fungal cell membrane, causing intracellular components to leak, with subsequent fungal cell death. DOC for severe or disseminated histoplasmosis.
Antifungal agents, azoles
Class Summary
The azole antifungal agents are divided into 2 groups: imidazoles and triazoles. The imidazoles are an older group and include miconazole, ketoconazole, and clotrimazole. The triazoles consist of fluconazole; itraconazole; and the new second-generation azoles ravuconazole (investigational in the United States), voriconazole, and posaconazole.
Itraconazole is more effective than ketoconazole or fluconazole for treatment of histoplasmosis. It is also effective for long-term suppression of histoplasmosis in patients with AIDS.
Voriconazole and posaconazole may be useful in patients who are intolerant of or who fail treatment with AmB or itraconazole. In vitro studies with voriconazole and posaconazole have shown the activity of these agents against H capsulatum, Blastomyces dermatitidis, and Coccidioides immitis. Data from a few animal studies have verified their efficacy in vivo. [22, 23]
Posaconazole is reported to be effective for histoplasmosis in a small number of patients. In a case series, 6 of 7 patients were successfully treated with posaconazole. [24] Four of these 6 patients had disseminated infection, and, in all, other therapy failed or was intolerable.
Phase 3 clinical trials for the treatment of invasive fungal infections have been completed, and the US Food and Drug Administration recently approved posaconazole for the prophylaxis of invasive Aspergillus and Candida infections in high-risk, severely immunocompromised patients aged 13 years or older.
Itraconazole (Sporanox)
Synthetic triazole antifungal agent. Can be used in CPH, but relapse rate higher than with amphotericin B.
Ketoconazole (Nizoral)
Synthetic imidazole antifungal agent. Can be used for CPH, but relapse rate higher than that of amphotericin B.
Fluconazole (Diflucan)
Synthetic triazole antifungal with low plasma protein binding. CNS penetration better than that of imidazoles.
Posaconazole (Noxafil)
Triazole antifungal agent. Blocks ergosterol synthesis by inhibiting lanosterol 14-alpha-demethylase and the accumulation of sterol precursors. Action disrupts cell membrane. Available as PO susp 200 mg/5 mL. Indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.
NSAIDs
Class Summary
NSAIDs have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may include inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions. A brief course of NSAIDs may be required for patients who develop rheumatologic symptoms.
Naproxen (Aleve, Naprosyn)
For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.
Ibuprofen (Motrin, Advil, Ibuprin)
Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
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Hilar lymphadenopathy in an 11-year-old child.
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Map demonstrates the distribution of histoplasmin skin-test positivity by region. Used with permission from the American Thoracic Society.
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Hematoxylin and eosin stain of infected lung tissue. Histoplasma organisms appear to have a false capsule.
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Starling roost in Alabama.
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Acute pulmonary syndrome in a 16-year-old female adolescent.
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Fibrosing mediastinitis with mediastinal widening and tracheal deviation.
