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

ACUTE

mild to moderate coccidioidal pneumonia (non-pregnant; without HIV)

1st line – observation

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ACUTE
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mild to moderate coccidioidal pneumonia (non-pregnant; without HIV)
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without risk factors for dissemination; symptoms improving
1st line – 

observation

For patients without risk factors for dissemination no treatment is required. Often, by the time the diagnosis is made‚ symptoms have improved or resolved.[5][46]

Close clinical, serological, and radiographic follow-up is indicated and treatment in the form of an azole antifungal (e.g., fluconazole, itraconazole) should be considered if symptoms are increasing with time.[5]

1st line – azole antifungal

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ACUTE
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mild to moderate coccidioidal pneumonia (non-pregnant; without HIV)
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without risk factors for dissemination; symptoms worsening
1st line – 

azole antifungal

Following close clinical, serological, and radiographic follow-up, treatment in the form of an azole antifungal (e.g., fluconazole or itraconazole) should be considered if symptoms are increasing with time.[5]

Treatment course is typically for 3-6 months.[5]

Primary options

fluconazole: 400-800 mg orally/intravenously once daily

OR

itraconazole: 200 mg orally twice daily

1st line – observation ± azole antifungal

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ACUTE
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mild to moderate coccidioidal pneumonia (non-pregnant; without HIV)
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with risk factors for dissemination (African-American, Filipino, immunocompromised, or diabetes mellitus)
1st line – 

observation ± azole antifungal

Patients with risk factors for dissemination (African-Americans, Filipinos, immunocompromised patients, or patients with diabetes mellitus) should be closely monitored with clinical, serological, and radiographic follow-up, or may be treated prophylactically with fluconazole or itraconazole.[5]

Treatment course is typically for 3-6 months.[5]

Primary options

fluconazole: 400-800 mg orally/intravenously once daily

OR

itraconazole: 200 mg orally twice daily

mild to moderate coccidioidal pneumonia (non-pregnant; with HIV)

1st line – azole antifungal

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ACUTE
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mild to moderate coccidioidal pneumonia (non-pregnant; with HIV)
1st line – 

azole antifungal

​For clinically mild to moderate pulmonary coccidioidomycosis (e.g., focal coccidioidal pneumonia), oral fluconazole or itraconazole are the preferred options for immunocompetent and immunocompromised individuals.[23]

Alternative azoles include isavuconazole, voriconazole, and posaconazole, although data are limited.[23]

Treatment course is typically for 3-6 months.[5]

Primary options

fluconazole: 400 mg orally once daily

OR

itraconazole: 200 mg orally three times daily for 3 days, followed by 200 mg twice daily

Secondary options

voriconazole: ​400 mg orally twice daily on day 1, followed by 200 mg twice daily

OR

posaconazole: 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily

OR

isavuconazole: 200 mg orally three times daily for 6 doses, followed by 200 mg once daily

severe or diffuse coccidioidal pneumonia (non-pregnant; without HIV)

1st line – azole antifungal or amphotericin-B

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ACUTE
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severe or diffuse coccidioidal pneumonia (non-pregnant; without HIV)
1st line – 

azole antifungal or amphotericin-B

Indicators of severe infection include: symptoms lasting >2 months; weight loss >10% of body weight; night sweats lasting >3 weeks; extensive pulmonary infiltrates (bilateral disease, persistent hilar adenopathy); inability to work, age >55 years; and serology titre >1:16.[5]

The goal of therapy is to gain control of the infection as quickly as possible and ideally prevent the establishment of an extrapulmonary focus of infection.[5] The risks of not treating include progressive pulmonary and extrapulmonary infection that may result in severe morbidity or death.

Patients are treated with either fluconazole or itraconazole daily for 3 to 6 months.[5] If a patient's symptoms are not improving with an azole antifungal, therapy can be switched to amphotericin-B.[5]

Azole antifungal therapy is recommended for ongoing treatment and, therefore, if amphotericin-B was used initially, treatment can be switched to fluconazole or itraconazole after several weeks or when the patient is stable.

Treatment course is typically for 3-6 months, but can vary.[5]

Primary options

fluconazole: 400-800 mg orally/intravenously once daily

OR

itraconazole: 200 mg orally twice daily

Secondary options

amphotericin B lipid complex: 3-5 mg/kg intravenously every 24 hours

OR

amphotericin B liposomal: 3-5 mg/kg intravenously every 24 hours

OR

amphotericin B deoxycholate: 0.7 to 1 mg/kg/day intravenously every 24 hours

severe or diffuse coccidioidal pneumonia (non-pregnant; with HIV)

1st line – amphotericin-B + azole antifungal

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ACUTE
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severe or diffuse coccidioidal pneumonia (non-pregnant; with HIV)
1st line – 

amphotericin-B + azole antifungal

​For severe pulmonary coccidioidomycosis (e.g., diffuse pulmonary infiltrates) or for extrapulmonary nonmeningeal coccidioidomycosis, intravenous amphotericin-B deoxycholate or liposomal amphotericin-B should be considered.[23]

Therapy should be switched to an oral azole after clinical improvement and should be continued for at least 12 months. The decision to discontinue therapy should be made by an infectious diseases consultant, based on clinical and serological response.[23]

Treatment course is typically for at least 12 months.[5]

Primary options

amphotericin B deoxycholate: 0.7 to 1 mg/kg intravenously every 24 hours

OR

amphotericin B liposomal: 3-5 mg/kg intravenously every 24 hours

Secondary options

fluconazole: 400 mg orally once daily

OR

itraconazole: 200 mg orally twice daily

pulmonary nodule (non-pregnant)

1st line – observation

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ACUTE
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pulmonary nodule (non-pregnant)
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radiographically stable in healthy patient
1st line – 

observation

A radiographically stable nodule (not enlarging with time) due to coccidioidomycosis (as determined by non-invasive or invasive means such as fine-needle biopsy or nodule resection) in an otherwise healthy (non-immunosuppressed) person who is asymptomatic requires no treatment.[5][46]​ Treatment is the same regardless of HIV status.​​​

If the abnormality can be seen and measured on chest x-ray, then no further imaging is necessary. If more precision is needed, or the abnormality cannot be seen on chest x-ray, CT is recommended.

Follow-up can be every 3 to 4 months for the first year, then every 6 months for the second year. If the lesion is radiographically stable, it will not require long-term follow-up.

1st line – azole antifungal

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ACUTE
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pulmonary nodule (non-pregnant)
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enlarging with active infection
1st line – 

azole antifungal

A patient with a coccidioidal pulmonary nodule that begins to enlarge should be evaluated by serology and sputum culture to assess whether the infection is active. If infection is active, treatment with fluconazole or itraconazole is recommended.[5]​ Treatment is the same regardless of HIV status.

Treatment is typically continued until a clinical or serological response is seen.[5]

Primary options

fluconazole: 400-800 mg orally/intravenously once daily

OR

itraconazole: 200 mg orally twice daily

asymptomatic pulmonary cavity (non-pregnant)

1st line – observation

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ACUTE
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asymptomatic pulmonary cavity (non-pregnant)
1st line – 

observation

For an asymptomatic coccidioidal cavity no treatment is indicated, but periodic follow-up should be performed to assure stability, over an indefinite period of time.[5] Some cavities will close over time with no need for treatment. Treatment is the same regardless of HIV status.

If the abnormality can be seen and measured on chest x-ray, then no further imaging is necessary. If more precision is needed, or the abnormality cannot be seen on chest x-ray, CT is recommended.

Follow-up can be every 3 to 4 months for the first year, then every 6 months for the second year. Periodic follow-up thereafter can be 6 to 12 months. The interval is judged on whether the patient is doing well, and if the cavity is stable or smaller over time.

Patients may require follow-up sooner in the event of any new or recurrent respiratory symptoms.

Consider – surgical resection

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ACUTE
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asymptomatic pulmonary cavity (non-pregnant)
Consider – 

surgical resection

Additional treatment recommended for SOME patients in selected patient group

For asymptomatic cavities that persist >2 years, are adjacent to the pleura, or are enlarging, resection can be considered to avoid complications associated with the cavity, such as secondary bacterial or fungal infection, or cavity rupture.[41]

symptomatic pulmonary cavity (non-pregnant)

1st line – azole antifungal

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ACUTE
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symptomatic pulmonary cavity (non-pregnant)
1st line – 

azole antifungal

Symptomatic cavities may be accompanied by local pain or discomfort, haemoptysis, secondary bacterial or fungal infection, or cavity rupture.​ Treatment is the same regardless of HIV status.

Fluconazole or itraconazole may alleviate symptoms but are unlikely to result in cavity closure and symptoms may recur with treatment cessation.[5]

Treatment is typically for 3-6 months or longer.[5]

Primary options

fluconazole: 400 mg orally/intravenously once daily

OR

itraconazole: 200 mg orally twice daily

Consider – surgical resection

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ACUTE
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symptomatic pulmonary cavity (non-pregnant)
Consider – 

surgical resection

Additional treatment recommended for SOME patients in selected patient group

Symptomatic cavities may be accompanied by local pain or discomfort, haemoptysis, secondary bacterial or fungal infection, or cavity rupture.

Surgical resection may be considered to alleviate symptoms.[41]

chronic progressive fibrocavitary coccidioidomycosis (non-pregnant)

1st line – azole antifungal or amphotericin-B

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ACUTE
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chronic progressive fibrocavitary coccidioidomycosis (non-pregnant)
1st line – 

azole antifungal or amphotericin-B

Initial treatment consists of fluconazole or itraconazole to alleviate symptoms, and to prevent further infection and fibrosis, and loss of lung function.[5]​ Treatment is the same regardless of HIV status.

If there is no response to initial treatment, options include increasing the dose, switching to an alternative azole such as voriconazole or posaconazole (both of which have been reported to have efficacy in selected patients failing traditional treatment), or switching to amphotericin-B.[5][47][48][49][50][51][52]

Treatment is typically continued for 12 months or until a response is seen.[5]

Primary options

fluconazole: 400-800 mg orally/intravenously once daily

OR

itraconazole: 200 mg orally twice daily

Secondary options

voriconazole: 400 mg orally twice daily on day 1, followed by 200 mg twice daily

OR

posaconazole: 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily; 400 mg orally (suspension) twice daily

OR

amphotericin B lipid complex: 3-5 mg/kg intravenously every 24 hours

OR

amphotericin B liposomal: 3-5 mg/kg intravenously every 24 hours

OR

amphotericin B deoxycholate: 0.7 to 1 mg/kg intravenously every 24 hours

skin and soft tissue coccidioidomycosis (non-pregnant)

1st line – azole antifungal or amphotericin-B

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ACUTE
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skin and soft tissue coccidioidomycosis (non-pregnant)
1st line – 

azole antifungal or amphotericin-B

Treatment is aimed at alleviating symptoms, controlling infection, and limiting the destruction of tissues and damage to organ function.[5] Treatment of skin and soft tissue infections is commonly associated with response rates ranging from 25% to 91%, with relapse rates as high as 50%.[53]​ Treatment is the same regardless of HIV status.

Initial treatment should include fluconazole or itraconazole.[5] Treatment is continued until a response is seen clinically and serologically, which can take months to years. After treatment is discontinued, close follow-up is needed to monitor for relapse.[5]

If there is no response to initial treatment, options include increasing the dose, switching to an alternative azole such as voriconazole or posaconazole (both of which have been reported to have efficacy in selected patients failing traditional treatment), or switching to amphotericin-B.[5][47][48][49][50][51][52]

Treatment is continued until a clinical or serological response is seen, typically for at least 6-12 months.[5]

Primary options

fluconazole: 400-800 mg orally/intravenously once daily

OR

itraconazole: 200 mg orally twice daily

Secondary options

voriconazole: 400 mg orally twice daily on day 1, followed by 200 mg twice daily

OR

posaconazole: 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily; 400 mg orally (suspension) twice daily

OR

amphotericin B lipid complex: 3-5 mg/kg intravenously every 24 hours

OR

amphotericin B liposomal: 3-5 mg/kg intravenously every 24 hours

OR

amphotericin B deoxycholate: 0.7 to 1 mg/kg intravenously every 24 hours

Consider – surgical excision or debridement

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ACUTE
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skin and soft tissue coccidioidomycosis (non-pregnant)
Consider – 

surgical excision or debridement

Additional treatment recommended for SOME patients in selected patient group

Surgical excision or debridement is often needed as an adjunctive measure, especially if lesions are large, destructive, or impinging on critical structures.[5][53]​​ Surgical excision or debridement may also be indicated if lesions do not respond to drug treatment alone, or if they recur after completion of antifungal therapy.

skeletal coccidioidomycosis (non-pregnant)

1st line – azole antifungal or amphotericin-B

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ACUTE
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skeletal coccidioidomycosis (non-pregnant)
1st line – 

azole antifungal or amphotericin-B

Skeletal coccidioidomycosis is a chronic and progressive infection.[54] Treatment is given to limit the destruction of involved bones and adjacent structures (muscle, joint, supporting structures) and to limit loss of function. Treatment is the same regardless of HIV status.

A comparison of fluconazole and itraconazole in the treatment of skeletal coccidioidomycosis demonstrated slight superiority of itraconazole.[55] Initial treatment should therefore include itraconazole, if the patient is able to tolerate it. Fluconazole is an alternative. 

If no response to initial treatment, options include increasing the dose, switching to an alternative azole such as voriconazole or posaconazole (both of which have been reported to have efficacy in selected patients failing traditional treatment), or switching to amphotericin-B.[5][47][48][49][50][51][52]

Treatment is typically continued until a clinical or serological response is seen (usually at least 3 years or lifelong depending on disease severity).[5]

Primary options

itraconazole: 200 mg orally twice daily

OR

fluconazole: 800 mg orally/intravenously once daily

Secondary options

voriconazole: 400 mg orally twice daily on day 1, followed by 200 mg twice daily

OR

posaconazole: 300 mg orally (delayed-release tablet) twice daily on day 1, followed by 300 mg once daily; 400 mg orally (suspension) twice daily

OR

amphotericin B lipid complex: 3-5 mg/kg intravenously once daily every 24 hours

OR

amphotericin B liposomal: 3-5 mg/kg intravenously once daily every 24 hours

OR

amphotericin B deoxycholate: 0.7 to 1 mg/kg intravenously every 24 hours

Consider – surgical excision or debridement

Back
ACUTE
|
skeletal coccidioidomycosis (non-pregnant)
Consider – 

surgical excision or debridement

Additional treatment recommended for SOME patients in selected patient group

Surgical excision or debridement is often needed as an adjunctive measure.[5][54]​ Treatment is continued until a response is seen clinically and serologically, which can take months to years.

After treatment is discontinued, close follow-up is needed to monitor for relapse.[5][54]

coccidioidal meningitis (non-pregnant)

1st line – azole antifungal

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ACUTE
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coccidioidal meningitis (non-pregnant)
1st line – 

azole antifungal

Treatment is required to alleviate symptoms, control infection, limit destruction of tissue and neurological function, and prevent hydrocephalus.[5]​ Consultation with an experienced specialist is recommended. Treatment is the same regardless of HIV status.

Fluconazole is the preferred treatment but itraconazole has also shown efficacy.[5][23]​​[56]​​ If treatment is failing with either of these, then posaconazole, voriconazole, or isavuconazole is recommended.[5][23]

Azole treatment is continued indefinitely.​[5][23][46]

Primary options

fluconazole: 800-1200 mg orally/intravenously once daily

Secondary options

itraconazole: 200 mg orally two to four times daily

OR

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

Consider – intravenous liposomal amphotericin-B

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ACUTE
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coccidioidal meningitis (non-pregnant)
Consider – 

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 ill or have evidence of widespread extrameningeal dissemination.[23][57]​​

Primary options

amphotericin B liposomal: 3-5 mg/kg intravenously every 24 hours

2nd line – intrathecal amphotericin-B

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ACUTE
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coccidioidal meningitis (non-pregnant)
2nd line – 

intrathecal amphotericin-B

​Intrathecal amphotericin-B should be considered if the patient does not show response to azole therapy.[5][23][56]

This should be administered by a clinician who is experienced in this drug delivery technique.[23]

Intrathecal administration of amphotericin-B may be complicated by the neurotoxicity associated with the amphotericin-B deoxycholate formulation, and complications of the application of treatment (such as cisternal bleeding or bacterial infection of an Ommaya reservoir).[56]

Primary options

amphotericin B deoxycholate: consult specialist for guidance on intrathecal dose

pregnant

1st line – observation or amphotericin-B

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ACUTE
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pregnant
1st line – 

observation or amphotericin-B

Pregnant women with mild or resolving illness may be observed closely without treatment. Serial evaluations are needed to reassess the decision to treat or not treat.

Treatment is given to alleviate severe symptoms, control infection, and prevent extrapulmonary dissemination. Poor outcome is correlated with diagnosis later in pregnancy.[12]

Pregnant women are at increased risk of disseminated infection. However, unlike treatment of all other patient groups, azoles are not considered first-line because foetal abnormalities have been described.[12] Instead, if it is decided that the potential benefits of treating the infection outweigh the risks in a pregnant woman, amphotericin-B is given first-line.[5]

In pregnant women living with HIV, amphotericin-B deoxycholate or a lipid formulation of amphotericin-B is the preferred treatment for non-meningeal coccidioidomycosis during the first trimester. For coccidioidal meningitis, an infectious diseases specialist should be consulted for guidance on treatment of pregnant women with HIV.[23]

Following delivery of the child, treatment may be changed to fluconazole or another azole, in conjunction with effective methods of birth control.

Primary options

amphotericin B lipid complex: 3-5 mg/kg intravenously every 24 hours

OR

amphotericin B liposomal: 3-5 mg/kg intravenously every 24 hours

OR

amphotericin B deoxycholate: 0.7 to 1 mg/kg intravenously every 24 hours

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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

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