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 coccidioidal pneumonia (non-pregnant)

1st line – observation

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ACUTE
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mild coccidioidal pneumonia (non-pregnant)
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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 coccidioidal pneumonia (non-pregnant)
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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]

Primary options

fluconazole: 400 mg orally/intravenously once daily for 3-6 months

OR

itraconazole: 200 mg orally twice daily for 3-6 months

1st line – observation ± azole antifungal

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ACUTE
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mild coccidioidal pneumonia (non-pregnant)
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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]

Primary options

fluconazole: 400 mg orally/intravenously once daily for 3-6 months

OR

itraconazole: 200 mg orally twice daily for 3-6 months

severe or diffuse coccidioidal pneumonia (non-pregnant)

1st line – azole antifungal or amphotericin-B

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ACUTE
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severe or diffuse coccidioidal pneumonia (non-pregnant)
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.

Primary options

fluconazole: 400 mg orally/intravenously once daily for 3-6 months

OR

itraconazole: 200 mg orally twice daily for 3-6 months

Secondary options

amphotericin B lipid complex: 2-5 mg/kg intravenously once daily for 1-6 months

OR

amphotericin B liposomal: 2-5 mg/kg intravenously once daily for 1-6 months

OR

amphotericin B deoxycholate: 0.5 to 1.5 mg/kg/day intravenously given once daily or on alternate days for 1-6 months

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]​​

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]

Primary options

fluconazole: 400-800 mg orally/intravenously once daily, continued until a clinical or serological response is seen

OR

itraconazole: 200 mg orally twice daily, continued until a clinical or serological response is seen

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.

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.[5]

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

Primary options

fluconazole: 400 mg orally/intravenously once daily for 3-6 months or longer

OR

itraconazole: 200 mg orally twice daily for 3-6 months or longer

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

Primary options

fluconazole: 400-800 mg orally/intravenously once daily for at least 1 year or until a clinical or serological response is seen

OR

itraconazole: 200-400 mg orally twice daily for at least 1 year or until a clinical or serological response is seen

Secondary options

voriconazole: 6 mg/kg intravenously every 12 hours for 2 doses, followed by 4 mg/kg every 12 hours

OR

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

OR

amphotericin B lipid complex: 2-5 mg/kg intravenously once daily

OR

amphotericin B liposomal: 2-5 mg/kg intravenously once daily

OR

amphotericin B deoxycholate: 0.5 to 1.5 mg/kg/day intravenously given once daily or on alternate days

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]

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.

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]

Primary options

fluconazole: 400 mg orally/intravenously once daily initially, continued until a clinical or serological response is seen, increase to 800 mg/day according to response

OR

itraconazole: 200 mg orally twice daily initially, continued until a clinical or serological response is seen, increase to 400 mg twice daily according to response

Secondary options

voriconazole: 6 mg/kg intravenously every 12 hours for 2 doses, followed by 4 mg/kg every 12 hours

OR

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

OR

amphotericin B lipid complex: 2-5 mg/kg intravenously once daily

OR

amphotericin B liposomal: 2-5 mg/kg intravenously once daily

OR

amphotericin B deoxycholate: 0.5 to 1.5 mg/kg/day intravenously given once daily or on alternate days

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 medication 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.

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 medicine 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]

Primary options

itraconazole: 200 mg orally twice daily initially, continued until a clinical or serological response is seen, increase to 400 mg twice daily according to response

OR

fluconazole: 400-800 mg orally/intravenously once daily, continued until a clinical response is seen

Secondary options

voriconazole: 6 mg/kg intravenously every 12 hours for 2 doses, followed by 4 mg/kg every 12 hours

OR

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

OR

amphotericin B lipid complex: 2-5 mg/kg intravenously once daily

OR

amphotericin B liposomal: 2-5 mg/kg intravenously once daily

OR

amphotericin B deoxycholate: 0.5 to 1.5 mg/kg/day intravenously given once daily or on alternate days

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 or intrathecal amphotericin-B

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

azole antifungal or intrathecal amphotericin-B

Treatment is required to alleviate symptoms, control infection, limit destruction of tissue and neurological function, and prevent hydrocephalus.[5]

Fluconazole is the preferred treatment but itraconazole has also shown efficacy.[5][56] If treatment is failing with either of these, then voriconazole is recommended. Azole treatment is continued indefinitely.[5]

Intrathecal amphotericin-B (ITAMB) should be considered if the patient does not show response to azole therapy.[5][56] ITAMB may be complicated by neurotoxicity of amphotericin-B deoxycholate and complications of the application of treatment (such as cisternal bleeding or bacterial infection of an Ommaya reservoir).[56]

Primary options

fluconazole: 400-800 mg orally/intravenously once daily, continued until a clinical response is seen

OR

itraconazole: 200 mg orally twice daily

Secondary options

voriconazole: 4 mg/kg orally/intravenously every 12 hours

Tertiary options

amphotericin B deoxycholate: consult specialist for guidance on intrathecal dosing

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]

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: 2-5 mg/kg intravenously once daily

OR

amphotericin B liposomal: 2-5 mg/kg intravenously once daily

OR

amphotericin B deoxycholate: 0.5 to 1.5 mg/kg/day intravenously given once daily or on alternate days

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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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