Histoplasmosis
- Overview
- Theory
- Diagnosis
- Management
- Follow up
- Resources
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
latent asymptomatic disease (non-pregnant)
observation
In otherwise healthy people with small exposure to fungal spores, histoplasmosis manifests as an asymptomatic or clinically insignificant infection.
Localised, healed pulmonary histoplasmosis infection can calcify and persist long term as pulmonary nodules which are asymptomatic and are found incidentally during lung imaging. Antifungal therapy for pulmonary nodules is not recommended.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
acute pulmonary disease (non-pregnant)
observation
In immunocompetent patients, the symptoms are mild, usually abate within weeks of onset, and tend to resolve without specific treatment.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
azole antifungal
Data for treatment of pulmonary histoplasmosis in immunocompetent patients with symptoms lasting ≥4 weeks are lacking. Itraconazole may be given, particularly in the presence of ongoing symptoms that raise concern for the development of progressive, disseminated histoplasmosis.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com People with HIV who have a CD4 count ≥300 cells/mm3 should be managed in the same way an immunocompetent person without HIV.[25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
Voriconazole and posaconazole have good in vitro activity against histoplasmosis. They have been successfully used to treat a limited number of immunocompromised individuals with histoplasmosis.[25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis They can be considered as alternatives for individuals intolerant to itraconazole.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
Fluconazole demonstrates lower activity against the fungus and is less effective than itraconazole, and there have been reports of resistance emerging among patients receiving fluconazole therapy.[4]Thompson GR 3rd, Le T, Chindamporn A, et al. Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology. Lancet Infect Dis. 2021 Dec;21(12):e364-74. https://pmc.ncbi.nlm.nih.gov/articles/PMC9450022 http://www.ncbi.nlm.nih.gov/pubmed/34364529?tool=bestpractice.com Fluconazole is therefore reserved for patients who are intolerant to other azoles.
Therapeutic drug monitoring is recommended with azole antifungals. Serum levels of itraconazole are generally higher with the solution formulation, and this should be used for treatment whenever possible.
Azole antifungals are hepatotoxic. Therefore, liver enzymes should be checked before initiation of therapy; at weeks 1, 2, and 4 after initiating treatment; and every 3 months thereafter (if applicable) until end of therapy.
Azole antifungals have a number of potential drug-drug interactions; review the patient's drug history prior to administration.
Treatment course: 6 to 12 weeks.
Primary options
itraconazole: children: 2.5 to 5 mg/kg orally twice daily, maximum 200 mg/dose; adults: 200 mg orally three times daily for 3 days, followed by 200 mg once or twice daily
Secondary options
voriconazole: children: consult specialist for guidance on dose; adults: 400 mg orally twice daily on day 1, followed by 200 mg twice daily
OR
posaconazole: children: consult specialist for guidance on dose; adults: 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily
Tertiary options
fluconazole: children: 3-6 mg/kg orally once daily, maximum 200 mg/dose; adults: 800 mg orally once daily
azole antifungal
Immunocompromised patients should be started on antifungal therapy as soon as active histoplasmosis infection is suspected, due to their high risk of progression to disseminated histoplasmosis and the attendant complications.
Azole antifungals are recommended for these patients. Itraconazole is the preferred option. Voriconazole and posaconazole show good in vitro activity against histoplasmosis, and have been successfully used to treat a more limited number of immunocompromised patients with acute disease. They can be considered as alternative agents for individuals who cannot tolerate itraconazole.[4]Thompson GR 3rd, Le T, Chindamporn A, et al. Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology. Lancet Infect Dis. 2021 Dec;21(12):e364-74. https://pmc.ncbi.nlm.nih.gov/articles/PMC9450022 http://www.ncbi.nlm.nih.gov/pubmed/34364529?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
Fluconazole demonstrates lower activity against the fungus, and there have been reports of resistance emerging among patients receiving fluconazole therapy.[4]Thompson GR 3rd, Le T, Chindamporn A, et al. Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology. Lancet Infect Dis. 2021 Dec;21(12):e364-74. https://pmc.ncbi.nlm.nih.gov/articles/PMC9450022 http://www.ncbi.nlm.nih.gov/pubmed/34364529?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis Fluconazole is therefore reserved for patients who are intolerant of or refractory to other azoles.
Therapeutic drug monitoring is recommended with azole antifungals. Serum levels of itraconazole are generally higher with the solution formulation, and this should be used for treatment whenever possible.
Azole antifungals are hepatotoxic. Therefore, liver enzymes should be checked before initiation of therapy; at weeks 1, 2, and 4 after initiating treatment; and every 3 months thereafter (if applicable) until end of therapy.
Azole antifungals have a number of potential drug-drug interactions; review the patient's drug history prior to administration.
Treatment course: 6 to 12 weeks for people without HIV.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com People with HIV and acute pulmonary histoplasmosis who have a CD4 count <300 cells/mm3 are treated with itraconazole for at least 12 months.[25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis People with HIV who have a CD4 count ≥300 cells/mm3 should be managed in the same way an immunocompetent person without HIV.[25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
Primary options
itraconazole: children (without HIV): 2.5 to 5 mg/kg orally twice daily, maximum 200 mg/dose; children (with HIV): 2-5 mg/kg orally three times daily for 3 days, followed by 2-5 mg/kg twice daily, maximum 200 mg/dose; adults: 200 mg orally three times daily for 3 days, followed by 200 mg twice daily
Secondary options
voriconazole: children: consult specialist for guidance on dose; adults: 400 mg orally twice daily on day 1, followed by 200 mg twice daily
OR
posaconazole: children: consult specialist for guidance on dose; adults: 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily
Tertiary options
fluconazole: children: 3-6 mg/kg orally once daily, maximum 200 mg/dose; adults: 800 mg orally once daily
amphotericin-B
For these patients, intravenous amphotericin-B is required for 1 to 2 weeks before transitioning to an oral azole antifungal once stabilised.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
Liposomal amphotericin-B is the preferred formulation in adults, although other formulations may be used if liposomal amphotericin-B is unavailable or not tolerated.[4]Thompson GR 3rd, Le T, Chindamporn A, et al. Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology. Lancet Infect Dis. 2021 Dec;21(12):e364-74. https://pmc.ncbi.nlm.nih.gov/articles/PMC9450022 http://www.ncbi.nlm.nih.gov/pubmed/34364529?tool=bestpractice.com
In patients with HIV, liposomal amphotericin-B has been associated with a higher response rate and lower mortality than amphotericin-B deoxycholate.[33]World Health Organization. Guidelines for diagnosing and managing disseminated histoplasmosis among people living with HIV. 1 April 2020 [internet publication]. https://www.who.int/publications/i/item/9789240006430 [50]Murray M, Hine P. Treating progressive disseminated histoplasmosis in people living with HIV. Cochrane Database Syst Rev. 2020 Apr 28;(4):CD013594. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013594/full http://www.ncbi.nlm.nih.gov/pubmed/32343003?tool=bestpractice.com
Amphotericin-B deoxycholate is well tolerated in children and lipid formulations are not necessarily preferred.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
Amphotericin-B is associated with nephrotoxicity, hypokalaemic, anaemia, and infusion-related adverse reactions.
Primary options
amphotericin B liposomal: children and adults: 3-5 mg/kg/day intravenously
Secondary options
amphotericin B lipid complex: children and adults: 5 mg/kg/day intravenously
OR
amphotericin B deoxycholate: children and adults: 0.7 to 1 mg/kg/day intravenously
azole antifungal
Treatment recommended for ALL patients in selected patient group
Patients should be transitioned to an oral azole antifungal once they have stabilised. Itraconazole is the preferred option.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis After discharge from hospital, patients require continued treatment with itraconazole for at least 12 weeks or until the pulmonary infiltrates have resolved on chest x-ray.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
Voriconazole and posaconazole show good in vitro activity against histoplasmosis, and have been successfully used to treat a limited number of immunocompromised patients with acute disease. They can be considered as alternative agents for individuals who are unable to tolerate itraconazole.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
Fluconazole has a reduced efficacy as chronic maintenance therapy, but can be used in patients intolerant of, or refractory to, other azoles.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
Therapeutic drug monitoring is recommended with azole antifungals. Serum levels of itraconazole are generally higher with the solution formulation, and this should be used for treatment whenever possible.
Azole antifungals are hepatotoxic. Liver enzymes should be checked before initiation of therapy; at weeks 1, 2, and 4 after initiating treatment; and every 3 months thereafter (if applicable) until end of therapy.
Azole antifungals have a number of potential drug-drug interactions; review the patient's drug history prior to administration.
Primary options
itraconazole: children (without HIV) 2.5 to 5 mg/kg orally twice daily, maximum 200 mg/dose; children (with HIV): 2-5 mg/kg orally three times daily for 3 days, followed by 2-5 mg/kg twice daily, maximum 200 mg/dose; adults: 200 mg orally three times daily for 3 days, followed by 200 mg twice daily
Secondary options
voriconazole: children: consult specialist for guidance on dose; adults: 400 mg orally twice daily on day 1, followed by 200 mg twice daily
OR
posaconazole: children: consult specialist for guidance on dose; adults: 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily
Tertiary options
fluconazole: children: 3-6 mg/kg orally once daily, maximum 200 mg/dose; adults: 800 mg orally once daily
ventilatory support
Additional treatment recommended for SOME patients in selected patient group
Patients may become hypoxaemic and require ventilatory support.
chronic pulmonary disease (non-pregnant)
azole antifungal
In contrast to other infections, the distinction between acute and chronic histoplasmosis is determined by the presence or absence of underlying lung disease rather than duration of symptoms. Chronic histoplasmosis arises in a pre-existing lung cavity, and symptoms take months to years to become clinically obvious.
Treatment is the same for immunocompetent and immunocompromised patients. Chronic pulmonary histoplasmosis has not been described in paediatric populations.
For ambulatory patients with mild to moderate disease (i.e., those who do not require ventilator support), itraconazole has been found to be safe and effective in the treatment of chronic pulmonary histoplasmosis.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [24]Dismukes WE, Bradsher RW Jr, Cloud GC, et al. Itraconazole therapy for blastomycosis and histoplasmosis. NIAID Mycoses Study Group. Am J Med. 1992 Nov;93(5):489-97. http://www.ncbi.nlm.nih.gov/pubmed/1332471?tool=bestpractice.com However, relapse rates are high (9% to 15%); hence, long-term treatment is recommended.
Voriconazole and posaconazole show good in vitro activity against histoplasmosis, and have been successfully used to treat a limited number of immunocompromised patients with acute disease. They can be considered as alternative agents for individuals who are unable to tolerate itraconazole. [1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis Fluconazole can be used in patients intolerant of or refractory to other azoles.[4]Thompson GR 3rd, Le T, Chindamporn A, et al. Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology. Lancet Infect Dis. 2021 Dec;21(12):e364-74. https://pmc.ncbi.nlm.nih.gov/articles/PMC9450022 http://www.ncbi.nlm.nih.gov/pubmed/34364529?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
Therapeutic drug monitoring is recommended with azole antifungals. Serum levels of itraconazole are generally higher with the solution formulation, and this should be used for treatment whenever possible. Blood levels of itraconazole should be measured once steady state is reached (i.e., 2 weeks after initiation of therapy). Random serum concentrations should be between 1 and 10 micrograms/mL.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
Azole antifungals are hepatotoxic. Liver enzymes should be checked before initiation of therapy; at weeks 1, 2, and 4 after initiating treatment; and every 3 months thereafter (if applicable) until end of therapy.
Azole antifungals have a number of potential drug-drug interactions; review the patient's drug history prior to administration.
Chest x-ray should be obtained at 4- to 6-month intervals, and treatment should be continued for at least 12 months or until complete resolution on chest x-ray, whichever comes later.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
Primary options
itraconazole: adults: 200 mg orally three times daily for 3 days, followed by 200 mg once or twice daily
Secondary options
voriconazole: adults: 400 mg orally twice daily on day 1, followed by 200 mg twice daily
OR
posaconazole: adults: 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily
Tertiary options
fluconazole: adults: 800 mg orally once daily
amphotericin-B
In contrast to other infections, the distinction between acute and chronic histoplasmosis is determined by the presence or absence of underlying lung disease rather than duration of symptoms. Chronic histoplasmosis arises in a pre-existing lung cavity, and symptoms take months to years to become clinically obvious.
Treatment is the same for immunocompetent and immunocompromised patients. Chronic pulmonary histoplasmosis has not been described in paediatric populations.
For patients with severe disease (i.e., who become hypoxaemic and require ventilatory support (and are therefore hospitalised), intravenous amphotericin-B is recommended for 1 to 2 weeks before transitioning to an oral azole antifungal once stabilised.[33]World Health Organization. Guidelines for diagnosing and managing disseminated histoplasmosis among people living with HIV. 1 April 2020 [internet publication]. https://www.who.int/publications/i/item/9789240006430
Liposomal amphotericin-B is the preferred formulation, although other formulations may be used if liposomal amphotericin-B is unavailable or not tolerated.[4]Thompson GR 3rd, Le T, Chindamporn A, et al. Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology. Lancet Infect Dis. 2021 Dec;21(12):e364-74. https://pmc.ncbi.nlm.nih.gov/articles/PMC9450022 http://www.ncbi.nlm.nih.gov/pubmed/34364529?tool=bestpractice.com
Amphotericin-B is associated with nephrotoxicity, hypokalaemia, anaemia, and infusion-related adverse reactions.
Primary options
amphotericin B liposomal: adults: 3-5 mg/kg/day intravenously
Secondary options
amphotericin B lipid complex: adults: 5 mg/kg/day intravenously
OR
amphotericin B deoxycholate: adults: 0.7 to 1 mg/kg/day intravenously
azole antifungal
Treatment recommended for ALL patients in selected patient group
Patients should be transitioned toan oral azole antifungal once they have stabilised. Itraconazole is the preferred option.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis After discharge from hospital, patients require continued treatment with itraconazole for at least 12 months or until the pulmonary infiltrates have resolved on chest x-ray.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
Voriconazole and posaconazole show good in vitro activity against histoplasmosis, and have been successfully used to treat a limited number of immunocompromised patients with acute disease. They can be considered as alternative agents for individuals who are unable to tolerate itraconazole.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
Fluconazole has a reduced efficacy as chronic maintenance therapy, but can be used in patients intolerant of, or refractory to, other azoles.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
Therapeutic drug monitoring is recommended with azole antifungals. Serum levels of itraconazole are generally higher with the solution formulation, and this should be used for treatment whenever possible.
Azole antifungals are hepatotoxic. Liver enzymes should be checked before initiation of therapy; at weeks 1, 2, and 4 after initiating treatment; and every 3 months thereafter (if applicable) until end of therapy.
Azole antifungals have a number of potential drug-drug interactions; review the patient's drug history prior to administration.
Due to high rates of relapse, patients should be closely monitored for at least 1 year after treatment is discontinued.
Primary options
itraconazole: adults: 200 mg orally three times daily for 3 days, followed by 200 mg once or twice daily
Secondary options
voriconazole: adults: 400 mg orally twice daily on day 1, followed by 200 mg twice daily
OR
posaconazole: adults: 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily
Tertiary options
fluconazole: adults: 800 mg orally once daily
ventilatory support
Additional treatment recommended for SOME patients in selected patient group
Patients may become hypoxaemic and require ventilatory support.
disseminated disease (non-pregnant)
azole antifungal
Disseminated disease is defined as clinical illness that fails to improve after 3 weeks of observation and is accompanied by signs and symptoms of extrapulmonary involvement. Progressive disseminated histoplasmosis has a high fatality rate without therapy. Treatment is the same for immunocompetent and immunocompromised patients.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
Azole antifungals are recommended for patients with mild to moderate disseminated disease. Itraconazole for at least 12 months is the preferred treatment.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
Voriconazole and posaconazole show good in vitro activity against histoplasmosis, and have been successfully used to treat a limited number of immunocompromised patients with acute disease. They can be considered as alternative agents for individuals who cannot tolerate itraconazole.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
Fluconazole demonstrates lower activity against the fungus and is less effective than itraconazole, and there have been reports of resistance emerging among patients receiving fluconazole therapy.[4]Thompson GR 3rd, Le T, Chindamporn A, et al. Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology. Lancet Infect Dis. 2021 Dec;21(12):e364-74. https://pmc.ncbi.nlm.nih.gov/articles/PMC9450022 http://www.ncbi.nlm.nih.gov/pubmed/34364529?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis Fluconazole is therefore reserved for patients who are intolerant of or refractory to other azoles.
Therapeutic drug monitoring is recommended with azole antifungals. Serum levels of itraconazole are generally higher with the solution formulation, and this should be used for treatment whenever possible.
Azole antifungals are hepatotoxic. Liver enzymes should be checked before initiation of therapy; at weeks 1, 2, and 4 after initiating treatment; and every 3 months thereafter (if applicable) until end of therapy.
Azole antifungals have a number of potential drug-drug interactions; review the patient's drug history prior to administration.
Chest x-ray should be obtained at 4- to 6-month intervals, and treatment should be continued for at least 12 months or until complete resolution on chest x-ray, whichever comes later.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
Long-term treatment with itraconazole may be required after completion of treatment in immunocompromised patients.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com In people with HIV, itraconazole can safely be discontinued after at least 1 year if they are receiving highly active antiretroviral therapy, CD4 count is >150 cells/mL, blood culture results are negative, and Histoplasma serum and urine antigen levels are <2 nanograms/mL.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [33]World Health Organization. Guidelines for diagnosing and managing disseminated histoplasmosis among people living with HIV. 1 April 2020 [internet publication]. https://www.who.int/publications/i/item/9789240006430 [51]Goldman M, Zackin R, Fichtenbaum CJ, et al. Safety of discontinuation of maintenance therapy for disseminated histoplasmosis after immunologic response to antiretroviral therapy. Clin Infect Dis. 2004 May 15;38(10):1485-9. https://academic.oup.com/cid/article/38/10/1485/347524 http://www.ncbi.nlm.nih.gov/pubmed/15156489?tool=bestpractice.com [52]Myint T, Anderson AM, Sanchez A, et al. Histoplasmosis in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): multicenter study of outcomes and factors associated with relapse. Medicine (Baltimore). 2014 Jan;93(1):11-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616326 http://www.ncbi.nlm.nih.gov/pubmed/24378739?tool=bestpractice.com
Primary options
itraconazole: children (without HIV) 2.5 to 5 mg/kg orally twice daily, maximum 200 mg/dose; children (with HIV): 2-5 mg/kg orally three times daily for 3 days, followed by 2-5 mg/kg twice daily, maximum 200 mg/dose; adults: 200 mg orally three times daily for 3 days, followed by 200 mg twice daily
Secondary options
voriconazole: children: consult specialist for guidance on dose; adults: 400 mg orally twice daily on day 1, followed by 200 mg twice daily
OR
posaconazole: children: consult specialist for guidance on dose; adults: 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily
Tertiary options
fluconazole: children: 5-6 mg/kg orally twice daily, maximum 600 mg/day; adults: 800 mg orally once daily
amphotericin-B
Disseminated disease is defined as clinical illness that fails to improve after 3 weeks of observation and is accompanied by signs and symptoms of extrapulmonary involvement. Progressive disseminated histoplasmosis has a high fatality rate without therapy. Treatment is the same for immunocompetent and immunocompromised patients.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis Amphotericin-B for 1 to 2 weeks is the recommended initial treatment for patients with severe disseminated disease before transitioning to an oralzole antifungal once stabilised.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
Liposomal amphotericin-B is the preferred formulation in adults, although other formulations may be used if liposomal amphotericin-B is unavailable or not tolerated.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [4]Thompson GR 3rd, Le T, Chindamporn A, et al. Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology. Lancet Infect Dis. 2021 Dec;21(12):e364-74. https://pmc.ncbi.nlm.nih.gov/articles/PMC9450022 http://www.ncbi.nlm.nih.gov/pubmed/34364529?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
In patients with HIV, liposomal amphotericin-B has been associated with a higher response rate and lower mortality than amphotericin-B deoxycholate.[33]World Health Organization. Guidelines for diagnosing and managing disseminated histoplasmosis among people living with HIV. 1 April 2020 [internet publication]. https://www.who.int/publications/i/item/9789240006430 [50]Murray M, Hine P. Treating progressive disseminated histoplasmosis in people living with HIV. Cochrane Database Syst Rev. 2020 Apr 28;(4):CD013594. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013594/full http://www.ncbi.nlm.nih.gov/pubmed/32343003?tool=bestpractice.com
Amphotericin-B deoxycholate is well tolerated in children and lipid formulations are not necessarily preferred.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
Amphotericin-B is associated with nephrotoxicity, hypokalaemia, anaemia, and infusion-related adverse reactions.
Primary options
amphotericin B liposomal: children and adults: 3 mg/kg/day intravenously
Secondary options
amphotericin B lipid complex: children and adults: 5 mg/kg/day intravenously
OR
amphotericin B deoxycholate: children and adults: 0.7 to 1 mg/kg/day intravenously
azole antifungal
Treatment recommended for ALL patients in selected patient group
Patients should be transitioned to an oral azole antifungal once they have stabilised. Itraconazole is the preferred option.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis After discharge from hospital, patients require continued treatment with itraconazole for at least 12 months or until the pulmonary infiltrates have resolved on chest x-ray.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
Voriconazole and posaconazole show good in vitro activity against histoplasmosis, and have been successfully used to treat a limited number of immunocompromised patients with acute disease. They can be considered as alternative agents for individuals who cannot tolerate itraconazole.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
Fluconazole demonstrates lower activity against the fungus and is less effective than itraconazole, and there have been reports of resistance emerging among patients receiving fluconazole therapy.[4]Thompson GR 3rd, Le T, Chindamporn A, et al. Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology. Lancet Infect Dis. 2021 Dec;21(12):e364-74. https://pmc.ncbi.nlm.nih.gov/articles/PMC9450022 http://www.ncbi.nlm.nih.gov/pubmed/34364529?tool=bestpractice.com Fluconazole is therefore reserved for patients who are intolerant of or refractory to other azoles.
Therapeutic drug monitoring is recommended with azole antifungals. Serum levels of itraconazole are generally higher with the solution formulation, and this should be used for treatment whenever possible.
Azole antifungals are hepatotoxic. Liver enzymes should be checked before initiation of therapy; at weeks 1, 2, and 4 after initiating treatment; and every 3 months thereafter (if applicable) until end of therapy.
Azole antifungals have a number of potential drug-drug interactions; review the patient's drug history prior to administration.
Due to high rates of relapse, patients should be closely monitored for at least 1 year after treatment is discontinued.
Long-term treatment with itraconazole may be required after completion of treatment in immunocompromised patients.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com In people with HIV, itraconazole can safely be discontinued after at least 1 year if they are receiving highly active antiretroviral therapy, CD4 count is >150 cells/mL, blood culture results are negative, and Histoplasma serum and urine antigen levels are <2 nanograms/mL.[25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis [33]World Health Organization. Guidelines for diagnosing and managing disseminated histoplasmosis among people living with HIV. 1 April 2020 [internet publication]. https://www.who.int/publications/i/item/9789240006430 [51]Goldman M, Zackin R, Fichtenbaum CJ, et al. Safety of discontinuation of maintenance therapy for disseminated histoplasmosis after immunologic response to antiretroviral therapy. Clin Infect Dis. 2004 May 15;38(10):1485-9. https://academic.oup.com/cid/article/38/10/1485/347524 http://www.ncbi.nlm.nih.gov/pubmed/15156489?tool=bestpractice.com [52]Myint T, Anderson AM, Sanchez A, et al. Histoplasmosis in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): multicenter study of outcomes and factors associated with relapse. Medicine (Baltimore). 2014 Jan;93(1):11-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616326 http://www.ncbi.nlm.nih.gov/pubmed/24378739?tool=bestpractice.com
Primary options
itraconazole: children (without HIV) 2.5 to 5 mg/kg orally twice daily, maximum 200 mg/dose; children (with HIV): 2-5 mg/kg orally three times daily for 3 days, followed by 2-5 mg/kg twice daily, maximum 200 mg/dose; adults: 200 mg orally three times daily for 3 days, followed by 200 mg twice daily
Secondary options
voriconazole: voriconazole: children: consult specialist for guidance on dose; adults: 400 mg orally twice daily on day 1, followed by 200 mg twice daily
OR
posaconazole: children: consult specialist for guidance on dose; adults: 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily
Tertiary options
fluconazole: children: 5-6 mg/kg orally twice daily, maximum 600 mg/day; adults: 800 mg orally once daily
ventilatory support
Additional treatment recommended for SOME patients in selected patient group
Patients may become hypoxaemic and require ventilatory support.
mediastinal granuloma (non-pregnant)
observation
In some patients, mediastinal lymph nodes can coalesce over months to years to form a large, caseating, encapsulated mass following acute pulmonary histoplasmosis. Treatment is not indicated for asymptomatic patients.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
azole antifungal
In some patients, mediastinal lymph nodes can coalesce over months to years to form a large, caseating, encapsulated mass following acute pulmonary histoplasmosis. Symptomatic patients can be treated with itraconazole.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
Therapeutic drug monitoring is recommended with azole antifungals. Serum levels of itraconazole are generally higher with the solution formulation, and this should be used for treatment whenever possible.
Azole antifungals are hepatotoxic. Liver enzymes should be checked before initiation of therapy; at weeks 1, 2, and 4 after initiating treatment; and every 3 months thereafter (if applicable) until end of therapy.
Azole antifungals have a number of potential drug-drug interactions; review the patient's drug history prior to administration.
Primary options
itraconazole: adults: 200 mg orally three times daily for 3 days, followed by 200 mg once or twice daily for 6-12 weeks
corticosteroid + azole antifungal
Reactive structures can cause symptoms secondary to compression of mediastinal structures or form fistulous tracts with a bronchus, the oesophagus, or skin. In this situation, treatment with a corticosteroid such as prednisone in combination with itraconazole is required.[53]Massachusetts General Hospital. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 15-1991. A 48-year-old man with dysphagia, chest pain, fever, and a subcarinal mass. N Engl J Med. 1991 Apr 11;324(15):1049-56. http://www.ncbi.nlm.nih.gov/pubmed/2005943?tool=bestpractice.com
Therapeutic drug monitoring is recommended with azole antifungals. Serum levels of itraconazole are generally higher with the solution formulation, and this should be used for treatment whenever possible.
Azole antifungals are hepatotoxic. Liver enzymes should be checked before initiation of therapy; at weeks 1, 2, and 4 after initiating treatment; and every 3 months thereafter (if applicable) until end of therapy.
Azole antifungals have a number of potential drug-drug interactions; review the patient's drug history prior to administration.
Primary options
prednisolone: adults: 0.5 to 1 mg/kg/day orally once daily, taper dose gradually over 1-2 weeks, maximum 80 mg/day
and
itraconazole: adults: 200 mg orally three times daily for 3 days, followed by 200 mg once or twice daily for 6-12 weeks
surgery
Additional treatment recommended for SOME patients in selected patient group
Surgery may be indicated to relieve obstructive symptoms.[53]Massachusetts General Hospital. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 15-1991. A 48-year-old man with dysphagia, chest pain, fever, and a subcarinal mass. N Engl J Med. 1991 Apr 11;324(15):1049-56. http://www.ncbi.nlm.nih.gov/pubmed/2005943?tool=bestpractice.com
mediastinal fibrosis (non-pregnant)
observation + consideration of azole antifungal
Invasive fibrosis can sometimes encase mediastinal or hilar lymph nodes and cause airway and great vessel occlusion. Bilateral disease is uncommon but highly fatal.[54]Mocherla S, Wheat LJ. Treatment of histoplasmosis. Semin Respir Infect. 2001 Jun;16(2):141-8. http://www.ncbi.nlm.nih.gov/pubmed/11521246?tool=bestpractice.com
Antifungal and anti-inflammatory treatments are generally not considered helpful. Some clinicians recommend a 12-week course of itraconazole, although efficacy is not demonstrated.[55]Limper AH, Knox KS, Sarosi GA, et al; American Thoracic Society Fungal Working Group. An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011 Jan 1;183(1):96-128. https://www.atsjournals.org/doi/full/10.1164/rccm.2008-740ST?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed http://www.ncbi.nlm.nih.gov/pubmed/21193785?tool=bestpractice.com
Corticosteroids are not recommended and the role of antifibrotics is unknown.
intravascular stent
Additional treatment recommended for SOME patients in selected patient group
Intravascular stents can be used to ameliorate symptoms of superior vena cava compression.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [55]Limper AH, Knox KS, Sarosi GA, et al; American Thoracic Society Fungal Working Group. An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011 Jan 1;183(1):96-128. https://www.atsjournals.org/doi/full/10.1164/rccm.2008-740ST?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed http://www.ncbi.nlm.nih.gov/pubmed/21193785?tool=bestpractice.com
broncholithiasis (non-pregnant)
bronchoscopic or surgical removal of stones
Calcified lymph nodes from prior histoplasmosis infection can sometimes erode into the adjacent bronchus, causing haemoptysis and spitting of small chalk-like pieces (lithoptysis).[56]Goodwin RA, Loyd JE, Des Prez RM. Histoplasmosis in normal hosts. Medicine (Baltimore). 1981 Jul;60(4):231-66. http://www.ncbi.nlm.nih.gov/pubmed/7017339?tool=bestpractice.com
Bronchoscopic and sometimes surgical removal of stones is the treatment of choice.[56]Goodwin RA, Loyd JE, Des Prez RM. Histoplasmosis in normal hosts. Medicine (Baltimore). 1981 Jul;60(4):231-66. http://www.ncbi.nlm.nih.gov/pubmed/7017339?tool=bestpractice.com Antifungal therapy is not indicated.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [55]Limper AH, Knox KS, Sarosi GA, et al; American Thoracic Society Fungal Working Group. An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011 Jan 1;183(1):96-128. https://www.atsjournals.org/doi/full/10.1164/rccm.2008-740ST?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed http://www.ncbi.nlm.nih.gov/pubmed/21193785?tool=bestpractice.com
pericarditis (non-pregnant)
non-steroidal anti-inflammatory drug (NSAID)
Symptoms are typically caused by the host inflammatory response to pulmonary infection, rather than due to infection of the pericardial sac itself.[57]Young EJ, Vainrub B, Musher DM. Pericarditis due to histoplasmosis. JAMA. 1978 Oct 13;240(16):1750-1. http://www.ncbi.nlm.nih.gov/pubmed/691177?tool=bestpractice.com
Treatment with NSAIDs is sufficient for mild symptoms. NSAIDs are associated with an increased risk of cardiovascular thrombotic events and gastrointestinal toxicity (bleeding, ulceration, perforation). NSAIDs should be used at the lowest effective dose for the shortest effective treatment course. Gastroprotection (e.g., a proton-pump inhibitor) may be required.
Primary options
ibuprofen: adults: 600-800 mg orally every 8 hours or 600 mg every 6 hours initially for at least 24 hours until resolution of symptoms (typically up to 2 weeks), then decrease dose by 200-400 mg/dose every 1-2 weeks according to response, maximum 2400 mg/day
OR
aspirin: adults: 650-1000 mg orally every 8 hours for at least 24 hours until resolution of symptoms (typically up to 2 weeks), then decrease dose by 250-500 mg/dose every 1-2 weeks according to response, maximum 4000 mg/day
corticosteroid + azole antifungal
Patients with moderate to severe symptoms require treatment with a corticosteroid; in this circumstance, itraconazole should be co-administered to prevent any dissemination of the infection that may result from the immunosuppression.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
Therapeutic drug monitoring is recommended with azole antifungals. Serum levels of itraconazole are generally higher with the solution formulation, and this should be used for treatment whenever possible.
Azole antifungals are hepatotoxic. Liver enzymes should be checked before initiation of therapy; at weeks 1, 2, and 4 after initiating treatment; and every 3 months thereafter (if applicable) until end of therapy.
Azole antifungals have a number of potential drug-drug interactions; review the patient's drug history prior to administration.
Primary options
prednisolone: adults: 0.5 to 1 mg/kg/day orally once daily, taper dose gradually over 1-2 weeks, maximum 80 mg/day
and
itraconazole: adults: 200 mg orally three times daily for 3 days, followed by 200 mg once or twice daily for 6-12 weeks
pericardiocentesis
Additional treatment recommended for SOME patients in selected patient group
Pericardiocentesis may be needed in patients with haemodynamic compromise.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
rheumatological syndrome (non-pregnant)
non-steroidal anti-inflammatory drug (NSAID)
The host inflammatory response to acute pulmonary histoplasmosis can cause polyarthritis or arthralgia in up to 10% of patients.[58]Rosenthal J, Brandt KD, Wheat LJ, et al. Rheumatologic manifestations of histoplasmosis in the recent Indianapolis epidemic. Arthritis Rheum. 1983 Sep;26(9):1065-70. http://www.ncbi.nlm.nih.gov/pubmed/6615561?tool=bestpractice.com Affected patients may also develop erythema nodosum.
Treatment is usually with NSAIDs alone.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com NSAIDs are associated with an increased risk of cardiovascular thrombotic events and gastrointestinal toxicity (bleeding, ulceration, perforation). NSAIDs should be used at the lowest effective dose for the shortest effective treatment course. Gastroprotection (e.g., a proton-pump inhibitor) may be required.
Primary options
ibuprofen: adults: 400-800 mg orally every 6-8 hours when required, maximum 2400 mg/day
OR
naproxen: adults: 250-500 mg orally twice daily when required, maximum 1250 mg/day
OR
diclofenac potassium: adults: 50 mg orally (immediate-release) three times daily when required, maximum 150 mg/day
OR
indometacin: adults: 25-50 mg orally (immediate-release) three times daily when required, maximum 200 mg/day
corticosteroid + azole antifungal
Corticosteroids are rarely needed but have been used for symptoms refractory to non-steroidal anti-inflammatory drugs (NSAIDs). If corticosteroids are given, itraconazole should be co-administered to prevent any dissemination of the infection.[58]Rosenthal J, Brandt KD, Wheat LJ, et al. Rheumatologic manifestations of histoplasmosis in the recent Indianapolis epidemic. Arthritis Rheum. 1983 Sep;26(9):1065-70. http://www.ncbi.nlm.nih.gov/pubmed/6615561?tool=bestpractice.com [59]Medeiros AA, Marty SD, Tosh FE, et al. Erythema nodosum and erythema multiforme as clinical manifestations of histoplasmosis in a community outbreak. N Engl J Med. 1966 Feb 24;274(8):415-20. http://www.ncbi.nlm.nih.gov/pubmed/5904279?tool=bestpractice.com
Therapeutic drug monitoring is recommended with azole antifungals. Serum levels of itraconazole are generally higher with the solution formulation, and this should be used for treatment whenever possible.
Azole antifungals are hepatotoxic. Liver enzymes should be checked before initiation of therapy; at weeks 1, 2, and 4 after initiating treatment; and every 3 months thereafter (if applicable) until end of therapy.
Azole antifungals have a number of potential drug-drug interactions; review the patient's drug history prior to administration
Primary options
prednisolone: adults: 0.5 to 1 mg/kg/day orally once daily, taper dose gradually over 1-2 weeks, maximum 80 mg/day
and
itraconazole: adults: 200 mg orally three times daily for 3 days, followed by 200 mg once or twice daily for 6-12 weeks
meningoencephalitis (non-pregnant)
amphotericin-B
Up to 20% of patients with disseminated histoplasmosis demonstrate signs and symptoms of central nervous system involvement that include meningitis, encephalitis, and mass lesions of the brain or spinal cord.[60]Wheat LJ, Batteiger BE, Sathapatayavongs B. Histoplasma capsulatum infections of the central nervous system. A clinical review. Medicine (Baltimore). 1990 Jul;69(4):244-60. http://www.ncbi.nlm.nih.gov/pubmed/2197524?tool=bestpractice.com
Initial treatment is with liposomal amphotericin-B for 4 to 6 weeks, followed by transition to an oral azole antifungal.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
Amphotericin-B is associated with nephrotoxicity, hypokalaemia, anaemia, and infusion-related adverse reactions.
Primary options
amphotericin B liposomal: adults: 5 mg/kg/day intravenously for 4-6 weeks
azole antifungal
Treatment recommended for ALL patients in selected patient group
Following completion of amphotericin-B treatment, transition to oral azole antifungal maintenance therapy is required for at least 1 year and until resolution of cerebrospinal fluid abnormalities, including Histoplasma antigen levels.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
The preferred option is itraconazole.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis Voriconazole or fluconazole may be considered for patients who cannot tolerate itraconazole and are only moderately ill; clinical data is limited.[25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis
Therapeutic drug monitoring is recommended with azole antifungals. Serum levels of itraconazole are generally higher with the solution formulation, and this should be used for treatment whenever possible. Blood levels of itraconazole should be obtained to ensure adequate drug exposure.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com
Azole antifungals are hepatotoxic. Liver enzymes should be checked before initiation of therapy; at weeks 1, 2, and 4 after initiating treatment; and every 3 months thereafter (if applicable) until end of therapy.
Azole antifungals have a number of potential drug-drug interactions; review the patient's drug history prior to administration.
Primary options
itraconazole: adults: 200 mg orally three times daily for 3 days, followed by 200 mg two to three times daily
Secondary options
voriconazole: adults: 400 mg orally twice daily on day 1, then 200 mg orally twice daily
Tertiary options
fluconazole: adults: 800 mg orally once daily
pregnant
amphotericin-B
Azole antifungals are teratogenic in pregnancy; therefore, the preferred treatment for pregnant women is amphotericin-B for 4 to 6 weeks.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [25]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and the Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: histoplasmosis. Oct 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/histoplasmosis The baby should be monitored for clinical and laboratory evidence of histoplasmosis after birth.[1]Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25. https://academic.oup.com/cid/article/45/7/807/541502 http://www.ncbi.nlm.nih.gov/pubmed/17806045?tool=bestpractice.com [62]Moudgal VV, Sobel JD. Antifungal drugs in pregnancy: a review. Expert Opin Drug Saf. 2003 Sep;2(5):475-83. http://www.ncbi.nlm.nih.gov/pubmed/12946248?tool=bestpractice.com
Liposomal or lipid formulations are recommended. The deoxycholate formulation is an alternative in patients who are at a low risk for nephrotoxicity.
Amphotericin-B is associated with nephrotoxicity, hypokalaemia, anaemia, and infusion-related adverse reactions.
Primary options
amphotericin B liposomal: adults: 3-5 mg/kg/day intravenously
Secondary options
amphotericin B lipid complex: adults: 5 mg/kg/day intravenously
OR
amphotericin B deoxycholate: adults: 0.7 to 1 mg/kg/day intravenously
ventilatory support
Additional treatment recommended for SOME patients in selected patient group
Patients may become hypoxaemic and require ventilatory support.
Choose a patient group to see our recommendations
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
Use of this content is subject to our disclaimer