Fungal meningitis
- 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
cryptococcal meningitis
antifungal induction therapy
Treatment is started as soon as the diagnosis is made, because untreated disease is uniformly fatal.
Initial induction combination therapy with an amphotericin-B formulation and flucytosine is recommended in both HIV- and non-HIV-associated infection. The preferred regimen recommended by US guidelines for patients with HIV is 2 weeks of intravenous liposomal amphotericin-B plus oral flucytosine.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new Amphotericin-B deoxycholate can be used as an alternative formulation if risk of renal dysfunction is low or if cost is prohibitive.
For patients with HIV, especially in resource-limited settings, the World Health Organization (WHO) recommends an induction regimen that consists of a single high dose of liposomal amphotericin-B combined plus 14 days of flucytosine and fluconazole.[66]World Health Organization. Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV. June 2022 [internet publication]. https://www.who.int/publications/i/item/9789240052178 http://www.ncbi.nlm.nih.gov/pubmed/35797432?tool=bestpractice.com
Where liposomal amphotericin-B is not available, the WHO recommends 1 week of amphotericin-B deoxycholate and flucytosine, followed by 1 week of fluconazole.[66]World Health Organization. Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV. June 2022 [internet publication]. https://www.who.int/publications/i/item/9789240052178 http://www.ncbi.nlm.nih.gov/pubmed/35797432?tool=bestpractice.com Alternative induction regimens recommended by US guidelines and the WHO are 2 weeks of intravenous or oral fluconazole plus oral flucytosine, 2 weeks of intravenous amphotericin-B deoxycholate plus oral fluconazole, or 2 weeks of liposomal amphotericin-B plus oral fluconazole.[66]World Health Organization. Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV. June 2022 [internet publication]. https://www.who.int/publications/i/item/9789240052178 http://www.ncbi.nlm.nih.gov/pubmed/35797432?tool=bestpractice.com [67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new Other options included in US guidelines are amphotericin-B lipid complex plus flucytosine; amphotericin-B deoxycholate plus flucytosine followed by fluconazole; amphotericin-B deoxycholate plus flucytosine.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
Lipid formulations of amphotericin-B may be preferred for patients with, or at risk of, clinically significant renal dysfunction.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new [92]Botero Aguirre JP, Restrepo Hamid AM. Amphotericin B deoxycholate versus liposomal amphotericin B: effects on kidney function. Cochrane Database Syst Rev. 2015 Nov 23;(11):CD010481. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010481.pub2/full http://www.ncbi.nlm.nih.gov/pubmed/26595825?tool=bestpractice.com Renal and haematological profiles must be monitored closely (especially in HIV-related nephropathy). Renal impairment may be reduced by saline and fluid loading, provided that there are no contraindications.[114]Branch RA. Prevention of amphotericin B-induced renal impairment. A review on the use of sodium supplementation. Arch Intern Med. 1988 Nov;148(11):2389-94. http://www.ncbi.nlm.nih.gov/pubmed/3056312?tool=bestpractice.com
Potassium and magnesium must be monitored and replaced if necessary.
A fall in haemoglobin of around 20% occurs within 2 weeks of starting amphotericin-B, and transfusion may be required.[115]Bicanic T, Wood R, Meintjes G, et al. High-dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV-infected patients: a randomized trial. Clin Infect Dis. 2008 Jul 1;47(1):123-30. https://academic.oup.com/cid/article/47/1/123/375282 http://www.ncbi.nlm.nih.gov/pubmed/18505387?tool=bestpractice.com Thrombophlebitis is common.
Some experts recommend measurement of serum peak concentrations of flucytosine 2 hours after dosing after 3-5 doses have been administered, with optimal concentrations being 25-100 mg/L.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
The combination of amphotericin-B and flucytosine, compared with amphotericin-B alone, was associated with improved survival in cryptococcal meningitis; however, there was no survival benefit from combining amphotericin-B and fluconazole.[93]Day JN, Chau TT, Wolbers M, et al. Combination antifungal therapy for cryptococcal meningitis. N Engl J Med. 2013 Apr 4;368(14):1291-1302. http://www.nejm.org/doi/full/10.1056/NEJMoa1110404#t=article http://www.ncbi.nlm.nih.gov/pubmed/23550668?tool=bestpractice.com WHO guidelines note that flucytosine-containing regimens are superior and should be used where possible.[66]World Health Organization. Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV. June 2022 [internet publication]. https://www.who.int/publications/i/item/9789240052178 http://www.ncbi.nlm.nih.gov/pubmed/35797432?tool=bestpractice.com
Treatment of cryptococcal meningitis in HIV-infected patients is complicated by the development of immune reconstitution inflammatory syndrome in nearly 1 in 8 patients.[19]Jarvis JN, Bicanic T, Loyse A, et al. Determinants of mortality in a combined cohort of 501 patients with HIV-associated cryptococcal meningitis: implications for improving outcomes. Clin Infect Dis. 2014 Mar;58(5):736-45. https://academic.oup.com/cid/article/58/5/736/365633 http://www.ncbi.nlm.nih.gov/pubmed/24319084?tool=bestpractice.com
Primary options
amphotericin B liposomal: 3-4 mg/kg intravenously once daily for 2 weeks
-- AND --
flucytosine: 25 mg/kg orally four times daily for 2 weeks
OR
amphotericin B liposomal: 10 mg/kg intravenously as a single dose on day 1
-- AND --
flucytosine: 25 mg/kg orally four times daily for 2 weeks
and
fluconazole: 1200 mg orally once daily for 2 weeks
Secondary options
amphotericin B lipid complex: 5 mg/kg intravenously once daily for 2 weeks
and
flucytosine: 25 mg/kg orally four times daily for 2 weeks
OR
amphotericin B liposomal: 3-4 mg/kg intravenously once daily for 2 weeks
and
fluconazole: 800-1200 mg orally once daily for 2 weeks
OR
fluconazole: 1200 mg orally/intravenously once daily for 2 weeks
and
flucytosine: 25 mg/kg orally four times daily for 2 weeks
OR
amphotericin B deoxycholate: 0.7 to 1 mg/kg intravenously once daily for 2 weeks
and
fluconazole: 800-1200 mg orally once daily for 2 weeks
OR
amphotericin B deoxycholate: 0.7 to 1 mg/kg intravenously once daily for 2 weeks
and
flucytosine: 25 mg/kg orally four times daily for 2 weeks
OR
amphotericin B deoxycholate: 1 mg/kg intravenously once daily for 1 week
and
flucytosine: 25 mg/kg orally four times daily for 1 week
and
fluconazole: 1200 mg orally once daily for 1 week (after 1-week course of amphotericin B deoxycholate and flucytosine)
antiretroviral therapy (ART)
Additional treatment recommended for SOME patients in selected patient group
For patients with HIV infection, immediate initiation of ART is not recommended as there is an increased risk of mortality, thought to be caused by immune reconstitution inflammatory syndrome.[98]Boulware DR, Meya DB, Muzoora C, et al; COAT Trial Team. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med. 2014 Jun 26;370(26):2487-98. http://www.nejm.org/doi/full/10.1056/NEJMoa1312884#t=article http://www.ncbi.nlm.nih.gov/pubmed/24963568?tool=bestpractice.com [99]Eshun-Wilson I, Okwen MP, Richardson M, et al. Early versus delayed antiretroviral treatment in HIV-positive people with cryptococcal meningitis. Cochrane Database Syst Rev. 2018 Jul 24;(7):CD009012. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009012.pub3/full http://www.ncbi.nlm.nih.gov/pubmed/30039850?tool=bestpractice.com World Health Organization (WHO) and US guidelines recommend that ART should be started 4-6 weeks after initiation of antifungal treatment.[66]World Health Organization. Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV. June 2022 [internet publication]. https://www.who.int/publications/i/item/9789240052178 http://www.ncbi.nlm.nih.gov/pubmed/35797432?tool=bestpractice.com [67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
therapeutic drainage of cerebrospinal fluid (CSF)
Additional treatment recommended for SOME patients in selected patient group
The management of patients with raised intracranial pressure is an important aspect of the management of cryptococcal meningitis.[100]Graybill JR, Sobel J, Saag M, et al. Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis. Clin Infect Dis. 2000 Jan;30(1):47-54. https://academic.oup.com/cid/article/30/1/47/323550 http://www.ncbi.nlm.nih.gov/pubmed/10619732?tool=bestpractice.com
Current guidelines recommend therapeutic drainage of CSF if the CSF opening pressure is >25 cm H₂O.[66]World Health Organization. Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV. June 2022 [internet publication]. https://www.who.int/publications/i/item/9789240052178 http://www.ncbi.nlm.nih.gov/pubmed/35797432?tool=bestpractice.com The aim is to reduce the CSF closing pressure to <20 cm H₂O or 50% of the opening pressure, by serial daily lumbar punctures with withdrawal of large volumes of CSF (up to 30 mL/day; pressure checked after removal of each 10 mL of CSF).
If serial lumbar punctures over a number of days fail to control elevated intracranial pressure, a temporary lumbar drain or ventriculoperitoneal shunt may be considered.[101]Macsween KF, Bicanic T, Brouwer AE, et al. Lumbar drainage for control of cerebrospinal fluid pressure in cryptococcal meningitis: case report and review. J Infect. 2005 Nov;51(4):e221-4. http://www.ncbi.nlm.nih.gov/pubmed/16291274?tool=bestpractice.com
Medical approaches including the use of corticosteroids, acetazolamide, or mannitol are not recommended.
antifungal consolidation therapy
Treatment recommended for ALL patients in selected patient group
Consolidation therapy is with fluconazole.[66]World Health Organization. Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV. June 2022 [internet publication]. https://www.who.int/publications/i/item/9789240052178 http://www.ncbi.nlm.nih.gov/pubmed/35797432?tool=bestpractice.com [67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new Less toxic oral therapy facilitates continued treatment and prevention of relapse, while minimising the dose-dependent toxicity of amphotericin-B.
The optimal consolidation phase of treatment is an 8-week course of oral fluconazole.[66]World Health Organization. Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV. June 2022 [internet publication]. https://www.who.int/publications/i/item/9789240052178 http://www.ncbi.nlm.nih.gov/pubmed/35797432?tool=bestpractice.com [67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
US guidelines advise that patients with positive CSF cultures but who have clinically improved after 2 weeks of induction therapy should receive a higher dose (1200 mg/day) of fluconazole for consolidation therapy, and have repeat lumbar puncture in another 2 weeks.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new Alternatively, non-hospitalised patients can receive flucytosine plus fluconazole for an additional 2 weeks before starting single-drug consolidation therapy.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new The duration of consolidation therapy should be 8 weeks from the point at which CSF cultures are negative.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
Primary options
fluconazole: clinically stable and negative CSF cultures: 400 mg orally once daily; positive CSF cultures: 800 mg orally once daily, may increase to 1200 mg once daily after 2 weeks if CSF remains positive and patient is clinically stable
Secondary options
fluconazole: 1200 mg orally once daily
and
flucytosine: 25 mg/kg orally four times daily
antifungal maintenance therapy
Treatment recommended for ALL patients in selected patient group
After the 8-week consolidation phase, the patient should be switched to low-dose fluconazole for long-term maintenance therapy.[66]World Health Organization. Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV. June 2022 [internet publication]. https://www.who.int/publications/i/item/9789240052178 http://www.ncbi.nlm.nih.gov/pubmed/35797432?tool=bestpractice.com [67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
In patients with HIV-associated cryptococcal meningitis, maintenance therapy should be continued for at least 1 year. Treatment may be stopped in asymptomatic patients once the patient's CD4 count is 100 cells/microlitre or above and the viral RNA is undetectable on antiretroviral therapy (ART).[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
It is unclear how long patients with non-HIV-associated cryptococcal meningitis should receive maintenance therapy. In the absence of data, most patients, depending on response to antifungal treatment and reversibility of immunosuppression, are maintained on fluconazole for 6 to 12 months.
Primary options
fluconazole: 200 mg orally once daily
histoplasmal meningitis
liposomal amphotericin-B
May be isolated or as a component of disseminated histoplasmosis.
Initial therapy is with liposomal amphotericin-B for 4 to 6 weeks.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
Electrolytes are monitored (replace as required) and also renal function; however, nephrotoxicity is less with liposomal formulation compared with deoxycholate formulation.
Saline and fluid loading equivalent to 1 L normal saline may reduce nephrotoxicity.
Primary options
amphotericin B liposomal: 5 mg/kg/day intravenously for 4-6 weeks
maintenance therapy with azole antifungal
Treatment recommended for ALL patients in selected patient group
May be isolated or as a component of disseminated histoplasmosis.
Maintenance therapy is with itraconazole. Voriconazole may be given to people who are intolerant to itraconazole and are only moderately unwell. Fluconazole may be given if there is intolerance to both itraconazole and voriconazole.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
Given for at least 1 year and until resolution of cerebrospinal fluid (CSF) abnormalities and of CSF antigen (and serum and urine antigen if initially positive).
Itraconazole can be safely discontinued in people with HIV after at least 1 year if all of the following apply: HIV viral load is undetectable on stable antiretroviral therapy (ART), CD4 count is ≥150 cells/microlitre for at least 6 months in response to ART, fungal blood cultures are negative, and serum or urine Histoplasma antigen is below the level of quantification.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
Random itraconazole concentrations and trough voriconazole concentrations should be measured during treatment to reduce severity and frequency of adverse effects.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new Drug levels of itraconazole are usually monitored to also ensure adequate drug absorption and assess adherence. Low levels may prompt a dose increase, a switch to liquid formulation, or switch to an alternative azole antifungal.[27]Wheat LJ, Musial CE, Jenny-Avital E. Diagnosis and management of central nervous system histoplasmosis. Clin Infect Dis. 2005 Mar 15;40(6):844-52. https://academic.oup.com/cid/article/40/6/844/347054 http://www.ncbi.nlm.nih.gov/pubmed/15736018?tool=bestpractice.com
Primary options
itraconazole: 200 mg orally twice to three times daily
Secondary options
voriconazole: 400 mg orally twice daily initially on day 1, followed by 200 mg twice daily
Tertiary options
fluconazole: 800 mg orally once daily
coccidioidal meningitis
azole antifungal therapy
First-line therapy is usually fluconazole.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new [104]Galgiani JN, Catanzaro A, Cloud GA, et al. Fluconazole therapy for coccidioidal meningitis. The NIAID-Mycoses Study Group. Ann Intern Med. 1993 Jul 1;119(1):28-35. http://www.ncbi.nlm.nih.gov/pubmed/8498760?tool=bestpractice.com
Itraconazole is an acceptable alternative.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new Alternative oral agents for patients intolerant or unresponsive to fluconazole or itraconazole are posaconazole, voriconazole, and isavuconazole.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new [105]Restrepo A, Tobón A, Clark B, et al. Salvage treatment of histoplasmosis with posaconazole. J Infect. 2007 Apr;54(4):319-27. http://www.ncbi.nlm.nih.gov/pubmed/16824608?tool=bestpractice.com [106]Cortez KJ, Walsh TJ, Bennett JE. Successful treatment of coccidioidal meningitis with voriconazole. Clin Infect Dis. 2003 Jun 15;36(12):1619-22. https://academic.oup.com/cid/article/36/12/1619/299153 http://www.ncbi.nlm.nih.gov/pubmed/12802765?tool=bestpractice.com [107]Proia LA, Tenorio AR. Successful use of voriconazole for treatment of Coccidioides meningitis. Antimicrob Agents Chemother. 2004 Jun;48(6):2341. http://aac.asm.org/content/48/6/2341.full http://www.ncbi.nlm.nih.gov/pubmed/15155250?tool=bestpractice.com
Patients who respond to azole antifungal therapy should continue this treatment indefinitely.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
Primary options
fluconazole: 800-1200 mg orally/intravenously once daily
OR
itraconazole: 200 mg orally two to four times daily
Secondary options
posaconazole: 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily
OR
voriconazole: 200-400 mg orally twice daily
OR
isavuconazole: 200 mg orally three times daily for 6 doses, followed by 200 mg once daily
intravenous liposomal amphotericin-B
Additional treatment recommended for SOME patients in selected patient group
Consultation with a specialist is required prior to administration. Intravenous amphotericin-B on its own is ineffective as treatment for coccidioidal meningitis. However, it can be used as an adjunct to oral azole antifungal therapy in patients who are critically unwell or have evidence of widespread extrameningeal dissemination.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new [108]Mathisen G, Shelub A, Truong J, et al. Coccidioidal meningitis: clinical presentation and management in the fluconazole era. Medicine (Baltimore). 2010 Sep;89(5):251-84. https://journals.lww.com/md-journal/fulltext/2010/09000/coccidioidal_meningitis__clinical_presentation_and.1.aspx http://www.ncbi.nlm.nih.gov/pubmed/20827104?tool=bestpractice.com
Primary options
amphotericin B liposomal: 3-5 mg/kg intravenously every 24 hours
ventricular shunt replacement
Additional treatment recommended for SOME patients in selected patient group
Patients with hydrocephalus usually require ventricular shunt placement.
intrathecal amphotericin-B
Patients who do not respond to azole therapy may be treated with intrathecal amphotericin-B which should be used in consultation with a specialist and administered by a clinician experienced in this drug delivery technique.[67]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association of the Infectious Disease Society of America. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Jul 2025 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
Primary options
amphotericin B deoxycholate: consult specialist for guidance on intrathecal dose
ventricular shunt replacement
Additional treatment recommended for SOME patients in selected patient group
Patients with hydrocephalus usually require ventricular shunt placement.
candidal meningitis
amphotericin-B + flucytosine
Treatment should be started immediately after diagnosis, or empirically pending diagnostic test results in severely ill patients where candidal meningitis is suspected.
Flucytosine achieves good levels in the cerebrospinal fluid, and is additive with amphotericin-B against Candida species in vitro and in experimental infection. Liposomal amphotericin-B is preferred in patients with renal impairment.
Flucytosine's toxic effects on bone marrow and liver must be carefully monitored, preferably with frequent serum flucytosine levels.[70]Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Feb 15;62(4):e1-50. https://academic.oup.com/cid/article/62/4/e1/2462830 http://www.ncbi.nlm.nih.gov/pubmed/26679628?tool=bestpractice.com
Renal and haematological profiles of patients receiving amphotericin-B must be monitored closely. Renal impairment may be reduced by saline and fluid loading, provided no contraindication.[114]Branch RA. Prevention of amphotericin B-induced renal impairment. A review on the use of sodium supplementation. Arch Intern Med. 1988 Nov;148(11):2389-94. http://www.ncbi.nlm.nih.gov/pubmed/3056312?tool=bestpractice.com Electrolytes (potassium and magnesium) need monitoring and replacement if necessary.
A fall in haemoglobin of around 20% occurs within 2 weeks of starting amphotericin-B.[115]Bicanic T, Wood R, Meintjes G, et al. High-dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV-infected patients: a randomized trial. Clin Infect Dis. 2008 Jul 1;47(1):123-30. https://academic.oup.com/cid/article/47/1/123/375282 http://www.ncbi.nlm.nih.gov/pubmed/18505387?tool=bestpractice.com
Transfusion may be required in those with low baseline haemoglobin. Thrombophlebitis is common.
Primary options
amphotericin B deoxycholate: 0.7 to 1 mg/kg/day intravenously for 2-6 weeks
or
amphotericin B liposomal: 4-6 mg/kg/day intravenously for 2-6 weeks
-- AND --
flucytosine: 50-100 mg/kg/day orally given in divided doses every 6 hours for 2-6 weeks
removal of prosthesis
Additional treatment recommended for SOME patients in selected patient group
In neurosurgical patients with candidaemia, prosthetic devices and infected intravascular catheters should be removed, if at all possible.
maintenance therapy with fluconazole or voriconazole
Treatment recommended for ALL patients in selected patient group
Continuation of treatment with fluconazole may be considered, especially in patients with ongoing immunosuppression, or in patients who have responded to amphotericin-B and flucytosine but have developed drug-related toxicity. Maintenance therapy has been used in HIV-infected patients.
Voriconazole is an alternative for fluconazole-resistant isolates.
Due to the high risk of relapse, therapy should be continued for a minimum of 4 weeks after the resolution of all signs and symptoms associated with the infection. All cerebrospinal fluid analysis and radiological findings should also normalise prior to stopping antifungal therapy.
Primary options
fluconazole: 800 mg orally once daily
Secondary options
voriconazole: 200 mg orally twice daily
Exserohilum rostratum meningitis
antifungal therapy
Before the 2012 outbreak from contaminated methylprednisolone in the US, human infections with E rostratumwere exceedingly rare. Little is known about its management, especially when the central nervous system (CNS) is involved.
For patients with E rostratum meningitis, a minimum of 3 months of antifungal therapy is recommended, with up to 1 year of treatment recommended for patients with severe CNS involvement (e.g., arachnoiditis).[109]Centers for Disease Control and Prevention. Multistate outbreak of fungal meningitis and other infections: resources for clinicians. Oct 2015 [internet publication]. http://www.cdc.gov/hai/outbreaks/clinicians/index.html#rationale
However, despite an optimum course of therapy, relapse of E rostratum meningitis has been reported after resolution of symptoms and normalisation of CSF white blood cell count.[110]Smith RM, Tipple M, Chaudry MN, et al. Relapse of fungal meningitis associated with contaminated methylprednisolone. N Engl J Med. 2013 Jun 27;368(26):2535-6. http://www.nejm.org/doi/full/10.1056/NEJMc1306560 http://www.ncbi.nlm.nih.gov/pubmed/23718153?tool=bestpractice.com
Prolonged or lifelong antifungal therapy may be required with relapsing fungal meningitis, depending on the nature of infection, the frequency of relapsing meningitis after cessation of antifungal therapy, the severity of CNS involvement, and the underlying immune status of the individual.
Treatment should be undertaken in consultation with an infectious diseases specialist.[109]Centers for Disease Control and Prevention. Multistate outbreak of fungal meningitis and other infections: resources for clinicians. Oct 2015 [internet publication]. http://www.cdc.gov/hai/outbreaks/clinicians/index.html#rationale
Aspergillus meningitis
voriconazole or amphotericin-B
Voriconazole is considered the primary treatment choice; lipid formulations of amphotericin-B are reserved for those intolerant or refractory to voriconazole.[111]Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Aug 15;63(4):e1-60. https://academic.oup.com/cid/article/63/4/e1/2595039 http://www.ncbi.nlm.nih.gov/pubmed/27365388?tool=bestpractice.com Long-term treatment is usually required depending on clinical response and immune status.
Primary options
voriconazole: 6 mg/kg intravenously every 12 hours on day 1, followed by 4 mg/kg intravenously every 12 hours, switch to oral therapy when clinical improvement; 200 mg orally twice daily
Secondary options
amphotericin B lipid complex: 5 mg/kg intravenously once daily
debridement of paranasal sinuses
Treatment recommended for ALL patients in selected patient group
Aggressive surgical debridement of paranasal fungal infection is a key to successful outcome of medical therapy.
mucormycosal meningitis
antifungal therapy
Liposomal amphotericin-B is the first-line agent in central nervous system (CNS) mucormycosis.[46]Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. 2019 Dec;19(12):e405-e421. http://www.ncbi.nlm.nih.gov/pubmed/31699664?tool=bestpractice.com Isavuconazole and posaconazole may be considered as second-line agents.[46]Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. 2019 Dec;19(12):e405-e421. http://www.ncbi.nlm.nih.gov/pubmed/31699664?tool=bestpractice.com [112]Marty FM, Ostrosky-Zeichner L, Cornely OA, et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis. 2016 Jul;16(7):828-37. http://www.ncbi.nlm.nih.gov/pubmed/26969258?tool=bestpractice.com [113]Vehreschild JJ, Birtel A, Vehreschild MJ, et al. Mucormycosis treated with posaconazole: review of 96 case reports. Crit Rev Microbiol. 2013 Aug;39(3):310-24. http://www.ncbi.nlm.nih.gov/pubmed/22917084?tool=bestpractice.com
Aggressive surgical debridement of paranasal fungal infection is key to the successful outcome of medical therapy.[46]Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. 2019 Dec;19(12):e405-e421. http://www.ncbi.nlm.nih.gov/pubmed/31699664?tool=bestpractice.com
Primary options
amphotericin B liposomal: 5-10 mg/kg intravenously every 24 hours
Secondary options
isavuconazole: 200 mg intravenously/orally every 8 hours for 6 doses, followed by 200 mg every 24 hours
OR
posaconazole: 300 mg intravenously every 12 hours on day 1, followed by 300 mg every 24 hours; 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily
debridement of paranasal sinuses
Treatment recommended for ALL patients in selected patient group
Aggressive surgical debridement of paranasal fungal infection is a key to successful outcome of medical therapy.[46]Cornely OA, Alastruey-Izquierdo A, Arenz D, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. 2019 Dec;19(12):e405-e421. http://www.ncbi.nlm.nih.gov/pubmed/31699664?tool=bestpractice.com
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