Approach

The main goal of treatment is to relieve clinical symptoms and signs, reduce anticoccidioidal antibodies, and return organ function to normal.[5] Preventing relapse is also a goal, but not always achievable with current treatment.[5] Treatment depends on the presentation and host category. Many coccidioidal infections are self-limited, mild, or asymptomatic, and do not require treatment.[5][46]​ However, some pulmonary‚ and nearly all extrapulmonary‚ infections will require treatment.[5][46]​ Non-resolving, progressive, or severe symptoms also warrant treatment.[5][46]

If patients are asymptomatic or have mild infection‚ but are at risk for disseminated infection (such as African-Americans, Filipinos, people who are immunocompromised, pregnant women, or patients with diabetes mellitus), they should either be monitored very closely or treated with antifungal therapy.[5] The patient is usually involved in the decision-making process. If the patient has symptomatic infection and is at risk for disseminated infection, treatment should be considered.[5]

Acute coccidioidal pneumonia: mild symptoms

For patients with no risk factors for dissemination, no treatment is required.[5][46]​ Often, by the time the diagnosis is made, symptoms have improved or resolved. Close clinical, serological, and radiographic follow-up is indicated, and treatment in the form of an azole antifungal (e.g., fluconazole or itraconazole) should be considered if symptoms are worsening with time.[5]

Patients with risk factors for dissemination (e.g., African-Americans, Filipinos, people who are immunocompromised, pregnant women‚ or patients with diabetes mellitus) are either monitored very closely or may be treated prophylactically with fluconazole or itraconazole.[5]

Acute coccidioidal pneumonia: severe and/or diffuse symptoms

Indicators of severe infection include:[5]

  • Symptoms lasting >2 months

  • Weight loss of >10%

  • Night sweats lasting >3 weeks

  • Extensive pulmonary infiltrates (bilateral disease, persistent hilar adenopathy)

  • Inability to work

  • Age >55 years

  • Serology titre >1:16.

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][46] 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.

Pulmonary nodule

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]

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]

A common differential for a pulmonary nodule is a malignant lesion, and therefore the nodule is often removed by a local wedge or, if necessary, lobar resection. If a nodule is determined to be due to coccidioidomycosis, a subsequent clinical assessment should be performed. Patients with risk factors for dissemination (such as immunosuppression) should have a directed evaluation for evidence of such dissemination, by review of symptoms, physical examination, and serology. If there is no evidence of another focus of coccidioidomycosis, no treatment is indicated.

Coccidioidal pulmonary cavity

Symptomatic cavities may be accompanied by local pain or discomfort, haemoptysis, secondary bacterial or fungal infection, or cavity rupture. Fluconazole or itraconazole may alleviate symptoms but are unlikely to result in cavity closure and symptoms may recur with treatment cessation.[5] Surgical resection may be considered to alleviate symptoms.[41]​​

For an asymptomatic cavity‚ no treatment is indicated, but periodic follow-up should be performed to assure stability, over an indefinite period of time.[5][46]​ Some cavities will close over time with no need for treatment.

For asymptomatic cavities that persist longer than 2 years, are adjacent to the pleura, or are enlarging, resection can be considered to avoid complications associated with the cavity.[41]

Chronic progressive fibrocavitary coccidioidomycosis

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][46]

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][46][47][48][49][50][51][52]

Skin and soft tissue coccidioidomycosis

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][46] Surgical excision or debridement is often needed as an adjunctive measure, especially if lesions are large, destructive, or impinging on critical structures.[5][53] 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][46][47][48][49][50][51][52] 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

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.[46] Fluconazole is an alternative.

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]

If there is 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][46][47][48][49][50][51][52]

Coccidioidal meningitis

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][46][56] If treatment is failing with either of these, then voriconazole is recommended. Azole treatment is continued indefinitely.[5][46] Intrathecal amphotericin-B (ITAMB) should then 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]

Pregnancy

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 coccidioidomycosis in a pregnant woman outweigh the risks, 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.

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