eMedicine Specialties > Dermatology > Fungal Infections
Coccidioidomycosis: Treatment & Medication
Updated: Jun 12, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
The management of primary respiratory infections resulting from C immitis is controversial because of the lack of prospective controlled trials. For many (if not most) patients, care may involve the periodic reassessment of symptoms and radiographic findings to ensure the resolution of the disease without antifungal treatment. Conversely, some authorities propose treatment in all symptomatic patients. Antifungal therapy should be initiated in the presence of concurrent risk factors (eg, HIV infection, organ transplant, high doses of corticosteroids) or unusually severe infections.
Desired outcomes of treatment include the resolution of signs and symptoms of infection, a reduction of serum concentrations of antibodies to C immitis, and the return of function in the involved organs. Also desirable is the prevention of a relapse of the illness when therapy is discontinued, although current therapy is often unable to achieve this goal.
The 3 components of the management of coccidioidal infections include the following: (1) assessing the need for intervention, (2) selecting the antifungal agents, and (3) selecting the surgical procedures.
The need for intervention, either medical or surgical, should be assessed. The severity of the disease should be determined in each patient. The particular lesion location, signs of adjacent tissue and organ involvement, and signs of disseminated disease should be evaluated. Common indicators of the severity of the disease include the following:
- Weight loss of more than 10%
- Intense night sweats persisting for longer than 3 weeks
- Infiltrates involving more than one half of 1 lung or portions of both lungs
- Prominent or persistent hilar adenopathy
- Concentrations of CF antibody to C immitis in a ratio of more than 1:16, as determined by using a reference method or an equivalent titer
- Failure to develop dermal hypersensitivity to coccidioidal antigens
- An inability to work
- Symptoms that persist for longer than 2 months
- African American, Filipino, or Mexican race
Antifungal agents should be selected for patients who may benefit from treatment. Before antifungal therapy was available, the natural history of initial pulmonary infections resulting from C immitis revealed that these infections spontaneously resolved in at least 95% of patients. To the authors' knowledge, randomized prospective clinical trails of antifungals have not been completed to determine whether drug therapy hastens the resolution of immediate symptoms or prevents subsequent complications.
Although most patients with primary infection recover without therapy, those with severe primary infection should generally receive chemotherapy. Patients with high CF titers require chemotherapy as well. Other criteria in determining the need for chemotherapy include the following:
- Symptoms persisting for longer than 6 weeks
- Prostration
- Extensive, enlarging, or persisting pulmonary involvement
- Persisting precipitins
- Negative skin test result
- Infancy
- Pregnancy (see Special Concerns)
- Debilitation
- Concurrent diseases likely to be adversely affected by coccidioidal infection (eg, diabetes, asthma, emphysema)
- Impairment of immune system
- Filipino, African American, or Hispanic race (see Race)
Once the disease has spread beyond the lungs, chemotherapy is always indicated. Surgical procedure may include the debridement and reconstruction of destructive lesions (see Surgical Care below). An effective vaccine needs to be developed. Dendritic cell – based and other vaccines against Coccidioides infection are being explored.
Surgical Care
The need for surgery is determined by the nature of specific lesions on a case-by-case basis because the manifestations, locations, and severity of progressive forms of coccidioidomycosis vary greatly among patients.
- In some patients, especially those with extensive skeletal or dermal involvement, debridement and drainage of the infected sites may be critical in controlling the infection.
- A reason for performing this procedure may be that the spherule wall, a strong stimulus for inflammation, cannot be degraded easily or cleared from large coccidioidal lesions by macrophages and other elements of the reticuloendothelial system.
- Therefore, even if therapy is effective in arresting fungal proliferation, fungal debris that is already present may continue to cause tissue destruction until it is surgically removed.
- Chronic pulmonary cavities respond poorly to antifungal therapy.
- Bacterial superinfection or hemoptysis due to the development of a fungus ball caused by Aspergillus species or C immitis itself may be complications.
- Cavitations may be progressive despite chemotherapy. In such cases, surgical resection may be valuable.
Consultations
Consultation with an infectious disease specialist is appropriate, especially in patients with concomitant HIV infection and in patients with CNS involvement.
Medication
In coccidioidomycosis, selection between amphotericin B and azole antifungals is based primarily on the severity of the infectious process, the degree of respiratory compromise in pulmonary infections, or the rate of progression of disseminated infections. Amphotericin B has more rapid onset of action compared with that of azole antifungals; therefore, despite its well-known toxicities, amphotericin B is the preferred initial therapy for patients with respiratory compromise or those whose condition is deteriorating rapidly. No evidence suggests that lipid formulations improve the effectiveness of amphotericin B suspended with deoxycholate. Azole antifungals are often used in patients with chronic disease because the ease of administration and lack of significant toxicities outweigh possible differences in the rates of response. During pregnancy, amphotericin B is the treatment of choice because fluconazole medications, and probably other azole antifungals, are teratogenic.
Patients with mild disease may not require treatment, and those with severe symptoms may experience disseminated disease during lapses in treatment.19
Clinical treatment guidelines are available from the Infectious Diseases Society of America.20 See Coccidioidomycosis for a summary.
Coccidioidomycosis therapy can be challenging in persons infected with HIV-1.21 Drug interactions between triazoles and antiretrovirals are a concern. The duration of treatment of coccidioidomycosis in those with HIV-1 infection should be either prolonged or life-long. Adherence to antiretroviral therapy may prevent recurrence of coccidioidomycosis. Clinical treatment guidelines for treating opportunistic infections are available from the Centers for Disease Control and Prevention and the Infectious Diseases Society of America for both children with HIV infection and adults and adolescents with HIV infection.22,23
A clinical trial, POS vs FLU for First Line Treatment of Coccidioidomycosis (Study P04558), is ongoing, but recruiting is complete.
Antifungal agents
Mechanism of action usually involves inhibiting pathways (enzymes, substrates, transport) necessary for sterol/cell membrane synthesis or altering the permeability of the cell membrane (polyenes) of the fungal cell. Fluconazole is most widely used because of its tolerability.24,25,26
Amphotericin B (Amphocin)
Polyene antibiotic produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols, such as ergosterol, in the fungal cell membrane, causing leakage of intracellular components with subsequent fungal cell death.
Adult
0.3-1 mg/kg/d IV; start with 0.25 mg/kg/d and increase by 5-10 mg/d; not to exceed 1.5 mg/kg/d
Severe infections: Start with maintenance dose; not to exceed 1.5 mg/kg/d
Pediatric
Administer as in adults
Antineoplastic agents may enhance potential for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; cyclosporine increases risk of renal toxicity
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor renal function, serum electrolytes (eg, magnesium, potassium), liver function, CBC counts, and hemoglobin concentrations; resume therapy at lowest dose (eg, 0.25 mg/kg) when therapy is interrupted >7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients who have neutropenia and are receiving leukocyte transfusions (separate administration of amphotericin infusion from leukocyte transfusion); fever and chills not uncommon after first few administrations; rare acute reactions include hypotension, bronchospasm, arrhythmias, and shock
Ketoconazole (Nizoral)
Fungistatic activity. Imidazole broad-spectrum antifungal agent; inhibits synthesis of ergosterol, causing leakage of cellular components and resulting in fungal cell death.
Adult
200 mg PO qd; increase to 400 mg PO qd if clinically indicated
Pediatric
<2 years: Not established
>2 years: 3.3-6.6 mg/kg/d PO once
Isoniazid may decrease bioavailability; rifampin coadministration decreases effects of either; may increase effect of anticoagulants; may increase toxicity of corticosteroids and cyclosporine (cyclosporine dosage can be adjusted); may decrease theophylline levels
Documented hypersensitivity; fungal meningitis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hepatotoxicity may occur; may reversibly decrease corticosteroid serum levels (adverse effects avoided with 200-400 mg/d); administer antacid, anticholinergics, or H2 blockers at least 2 h after administration
Fluconazole (Diflucan)
Fungistatic activity. Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, preventing conversion of lanosterol to ergosterol and thereby disrupting cellular membranes.
Adult
150 mg PO once or 400 mg qd, depending on severity of infection
Pediatric
3-6 mg/kg PO qd for 14-28 d or 6-12 mg/kg qd, depending on severity of infection
Hydrochlorothiazides may increase levels; long-term coadministration of rifampin may decrease levels; coadministration may decrease phenytoin clearance; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; coadministration may increase effects of anticoagulants; concurrent administration may increase cyclosporine concentrations
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adjust dose in renal insufficiency; monitor closely if rashes develop, and discontinue if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) with underlying medical conditions such as AIDS or malignancy and with multiple concomitant medications; not recommended in breastfeeding
Itraconazole (Sporanox)
Fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.
Adult
200 mg PO qd; not to exceed 400 mg/d; increase in 100-mg increments if no improvement (administer >200 mg/d in divided doses)
Alternatively, 200 mg IV bid for 4 doses, followed by 200 mg/d IV
Nail infections: 200 mg/d PO for 3-4 mo or pulse dosing of 400 mg/d PO for 1 wk each mo for 3-4 mo
Pediatric
Systemic fungal infection: 100 mg/d PO
Antacids may reduce absorption; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; high doses may increase tacrolimus and cyclosporine plasma concentrations; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (eg, lovastatin, simvastatin); coadministration with cisapride can cause cardiac rhythm abnormalities and death; may increase digoxin levels; coadministration may increase plasma levels of midazolam or triazolam; phenytoin and rifampin may reduce levels (phenytoin metabolism may be altered)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hepatic insufficiency
More on Coccidioidomycosis |
| Overview: Coccidioidomycosis |
| Differential Diagnoses & Workup: Coccidioidomycosis |
 Treatment & Medication: Coccidioidomycosis |
| Follow-up: Coccidioidomycosis |
| References |
| « Previous Page | Next Page » |
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Further Reading
Keywords
Valley fever, San Joaquin Valley fever, Coccidioides immitis, C immitis, arthroconidia, primary cutaneous coccidioidomycosis, respiratory infection, coccidioidal pneumonia, coccidioidal meningitis
