Histoplasmosis Medication

Updated: Sep 15, 2020
  • Author: Jazeela Fayyaz, DO; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Amphotericin B is indicated for pregnant women with histoplasmosis who require treatment.


The current Infectious Diseases Society of America guidelines recommend itraconazole for mild-to-moderate infection and amphotericin B for severe infection. [28] Itraconazole levels should be monitored starting two weeks after the start of treatment. levels greater than 10 mcg/mL should raise concern about toxicity. In addition, hepatic enzymes should be monitored as hepatotoxicity can occur. [27] The treatment success rate with itraconazole is 80-100%. [15]

Fluconazole is recommended as a second-line agent. Treatment success is approximately 63% with fluconazole; relapse rates may also be higher. [11] Resistance to fluconazole may be seen in AIDS patients with histoplasmosis.

Voriconazole and posaconazole are also second-line agents; currently, no clinical trials demonstrate benefit with voriconazole and posaconazole.

Ketoconazole is no longer recommended because of its toxicity.

Echinocandins are not active against histoplasmosis and should not be used. [28]

Patients with chronic cavitary pulmonary histoplasmosis should be treated for 1 year. [12]

Amphotericin B is the drug of choice for treating overwhelming acute pulmonary histoplasmosis, chronic pulmonary histoplasmosis, and all forms of progressive disseminated pulmonary histoplasmosis. If using amphotericin B for maintenance therapy for acute progressive disseminated histoplasmosis, continue weekly intravenous treatment in an outpatient setting.

Liposomal amphotericin B is preferred over the deoxycholate formulation.

The current Infectious Disease Society of America (IDSA) and American Thoracic Society (ATS) guidelines recommend the addition of intravenous methylprednisolone for severe acute pulmonary histoplasmosis.

Treatment is recommended for at least 1 year; immunosuppressed patients may need a longer duration of treatment. [15]

Patients with relapse of infection (10-15% of patients) after completion of therapy may require lifelong therapy. [15]

Anti-inflammatory drugs

Use NSAIDs when pericarditis is present.

Use steroids to decrease the severe hypersensitivity inflammatory response to histoplasmal antigens. Carefully monitor patients with systemic infections or sepsis and those who are immunosuppressed. Assess for signs of superinfection and worsening sepsis.



Class Summary

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

Amphotericin B (Fungizone)

Amphotericin B is the drug of choice for overwhelming acute pulmonary histoplasmosis, chronic pulmonary histoplasmosis, all forms of progressive disseminated histoplasmosis, meningitis, and endovascular histoplasmosis. It can be used as maintenance therapy for acute progressive disseminated histoplasmosis. Treatment with amphotericin alone without surgical intervention in endovascular histoplasmosis rarely is effective. It is also used after treatment failure with azoles.

Itraconazole (Sporanox, Tolsura)

Itraconazole has fungistatic activity. It is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP450-dependent synthesis of ergosterol, a vital component of fungal cell membranes.

Itraconazole can be used as a substitute for ketoconazole. Itraconazole can be used for mildly symptomatic or prolonged acute pulmonary histoplasmosis. It is used to treat cutaneous or rheumatologic manifestations in patients who are immunocompromised and in prolonged courses of illness. It can be used as an alternative to amphotericin B in the treatment of chronic pulmonary histoplasmosis or chronic and subacute progressive disseminated histoplasmosis. Unlike ketoconazole, it can be used as an alternate maintenance therapy after induction with amphotericin B in acute progressive disseminated histoplasmosis.

Voriconazole (Vfend)

Voriconazole is a triazole antifungal agent that inhibits fungal CYP450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.


Posaconazole is a triazole antifungal agent. It blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption. Posaconazole is available as an oral suspension (200 mg/5 mL). It is indicated for prophylaxis of invasive Aspergillus infections in patients at high risk because of severe immunosuppression.

Fluconazole (Diflucan)

Fluconazole is a second-line agent and generally does not have sufficient activity for histoplasmosis. It is a 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. Fluconazole has little affinity for mammalian cytochromes, which is believed to explain its low toxicity. It is available as a tablet for oral administration, as powder for oral suspension, and as a sterile solution for intravenous use. Fluconazole has fewer adverse effects and better tissue distribution than older systemic imidazoles.


Nonsteroidal Anti-inflammatory Drugs

Class Summary

Nonsteroidal anti-inflammatory drugs 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 exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions. They are commonly used to alleviate inflammation associated with pericarditis, as in histoplasmal pericarditis.

Ibuprofen (Motrin, Advil)

Ibuprofen inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.



Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Prednisone (Sterapred)

Prednisone is commonly used to decrease the hypersensitivity response to histoplasmal infection. High-dose steroids are used in patients with extensive maculopathy.