eMedicine Specialties > Emergency Medicine > Infectious Diseases
Coccidioidomycosis: Treatment & Medication
Updated: May 27, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Emergency Department Care
- Therapy is rarely started in the emergency department (ED); however, infectious disease consultants often expedite therapy in endemic areas.
- Therapies include amphotericin B and azoles, including ketoconazole and fluconazole.
Consultations
- Report cases to infectious disease and local health departments.
- Consultation with a pulmonologist is indicated.
Medication
In general, the severity and tempo of the disease usually dictates tempo of treatment. In patients with suspected or documented uncomplicated primary infection, treatment varies from careful observation to long-term azole therapy.
Some authors have suggested that empiric treatment may decrease the rate of disseminated infection, but this has not been proven in any controlled studies and no conclusive guidelines specify which uncomplicated infections need treatment. However, groups who are at risk for dissemination (eg, blacks, Filipinos, individuals with HIV or AIDS, individuals with diabetes mellitus, women in the third trimester of pregnancy) warrant more aggressive treatment. Typically, this may be accomplished with fluconazole except in pregnant women because azole antifungals are teratogenic. Pregnant women with suspected infection may be treated with amphotericin B. Currently, few randomized controlled trials have specifically looked at the efficacy of the different azoles. Galgiani et al compared fluconazole with itraconazole in a randomized controlled trial.7 Although no statistically significant difference was noted, itraconazole was associated with better outcomes in musculoskeletal disease.
Patients with more advanced disease require more aggressive treatment. In particular, patients who exhibit signs of meningitis need either intravenous antibiotic therapy with amphotericin unless otherwise contraindicated or high-dose azole therapy with or without intrathecal amphotericin. Some case reports have suggested that voriconazole or posaconazole may be therapeutic options in these patients;8,9 however, these reports are only anecdotal to date, and no comparative studies have been performed. Caspofungin in combination with fluconazole has been cited as beneficial in a case report of a 31-year-old Korean man with coccidioidal pneumonia.10 Steroids may be somewhat beneficial in patients with vasculitis.
Antifungal agents
The mechanism of action in these agents may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.
Amphotericin B (AmBisome, Fungizone)
Depending on concentration attained in body fluids and on fungal susceptibility, agent can be fungistatic or fungicidal. This polyene antibiotic produced by strain of Streptomyces nodosus changes membrane permeability by binding to sterols in fungal cell membrane; fungal cell death results.
Adult
0.5-1 mg/kg/d IV; not to exceed 2-4 g/dose
Pediatric
2.5 mg/kg/d IV
Antineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity increased with cyclosporine
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 such as magnesium and potassium, liver function, CBC count, and hemoglobin concentrations; resume therapy at lowest dose (eg, 0.25 mg/kg) when interrupted for >7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients with neutropenia receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion)
Fluconazole (Diflucan)
Synthetic bistriazole antifungal agent; highly selective inhibitor of fungal cytochrome P-450 and sterol C-14 alpha-demethylation with broad-spectrum activity.
Adult
200-400 mg PO qd
Pediatric
3-6 mg/kg PO qd for 14-28 d depending on severity of infection
Levels may increase with hydrochlorothiazides; levels may decrease with long-term coadministration of rifampin; may decrease phenytoin concentrations; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; may increase effects of anticoagulants; may increase cyclosporine concentration
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
Not recommended for breastfeeding mothers
Monitor closely if rashes develop and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis and fulminant hepatic failure (including death) with underlying medical conditions such as AIDS or a malignancy and while taking multiple concomitant medications
Ketoconazole (Nizoral)
Imidazole broad-spectrum antifungal agent. Impairs synthesis of ergosterol, allowing increased permeability and leakage of cellular components.
Adult
200-400 mg PO qd
Pediatric
Not established
Isoniazid may decrease bioavailability; coadministration with rifampin decreases effects of either drug; 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 dose of 200-400 mg/d)
Testosterone levels are reduced by doses of 800 mg/d and abolished by doses of 1600 mg/d (once therapy discontinued, levels return to baseline values); decreases ACTH-induced corticosteroid serum levels at high doses (to avoid these effects, closely follow recommended dose of 200-400 mg/d)
Requires acidity for dissolution and absorption (if antacids, anticholinergics, or H2-blockers are needed, give >2 h after ketoconazole)
Itraconazole (Sporanox)
Triazole analogue of ketoconazole
Adult
400-600 mg PO qd
Pediatric
Specific dosing in children with coccidioidomycosis not studied; in other antifungal regimen recommend dose is 5 mg/kg/d PO divided qd/bid; max dose 10 mg/kg/d
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 (lovastatin or 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 or suspected drug allergies or hypersensitivity; CHF or liver dysfunction
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
Use cautiously in patients with hepatic insufficiency
Voriconazole (Vfend)
Triazole antifungal agent that inhibits fungal cytochrome P450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.
Adult
200 mg PO bid or 3-6 mg/kg IV q12h
Pediatric
Not established
CYP450 2C19 (highest affinity), 2C9, and 3A4 (minor) substrate and inhibitor; CYP450 inducers (eg, rifampin) have shown to decrease steady state peak plasma levels by up to 93%; may increase serum levels of drugs metabolized by CYP450 2C19 or 2C9, of which some are contraindicated (eg, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids), others may need more frequent monitoring (eg, cyclosporine, tacrolimus, warfarin, HMG-CoA inhibitors, benzodiazepines, calcium channel blockers)
Documented hypersensitivity; CrCl <50 mL/min (decreased excretion of IV vehicle) if administering IV; coadministration with rifampin, rifabutin, carbamazepine, barbiturates, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Decrease maintenance dose in hepatic dysfunction; common adverse effects include visual disturbances, fever, rash, vomiting, nausea, diarrhea, headache, sepsis, peripheral edema, abdominal pain, rash (including Stevens-Johnson syndrome and phototoxicity), and respiratory disorder; rare cases of severe hepatotoxicity reported; administer PO dosage form 1 h ac or pc
Posaconazole (Noxafil)
Triazole antifungal agent that possesses structural similarities to itraconazole. Blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption. Available as PO susp (200 mg/5 mL). Indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.
Adult
200 mg (5 mL) PO tid with food or liquid nutritional supplement to enhance absorption
Pediatric
<13 years: Not established
>13 years: Administer as in adults
Metabolized via UDP glucuronidation; P-gp efflux substrate; CYP3A4 inhibitor
UDP-G inducers (eg, rifabutin, phenytoin) and drugs that increase gastric pH (eg, cimetidine) decrease serum levels (avoid concomitant use unless benefit outweighs risk)
Inhibits CYP3A4 and may elevate serum levels of cyclosporine, tacrolimus, sirolimus, rifabutin, midazolam, phenytoin, calcium channel blockers (eg, nifedipine, bepridil), HMG-CoA reductase inhibitors (eg, lovastatin, pravastatin), ergot alkaloids, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine, or vinca alkaloids (eg, vincristine, vinblastine)
Documented hypersensitivity; coadministration with ergot alkaloids; coadministration with CYP3A4 substrates likely to result in serious toxicities (eg, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine)
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
Common adverse effects include nausea, vomiting, diarrhea, rash, hypokalemia, thrombocytopenia, and elevated liver enzyme levels; closely monitor patients with severe diarrhea or vomiting for breakthrough fungal infections; rare adverse events include arrhythmias caused by QTc prolongation, bilirubinemia, or liver function impairment; caution with preexisting cardiac risk factors (eg, history of arrhythmia, hypokalemia, hypomagnesemia); food improves absorption and provides optimal serum concentration; shake well before use; administer with measuring spoon provided in package; avoid if breastfeeding
Caspofungin (Cancidas)
First of a new class of antifungal drugs (glucan synthesis inhibitors). Inhibits synthesis of beta-(1,3)-D-glucan, an essential component of fungal cell wall.
Adult
Not established; typical antifungal regimens suggest starting at 70 mg IV on day 1 followed by 50 mg IV qd
Pediatric
Not established
Coadministration with cyclosporine may increase risk of hepatotoxicity; carbamazepine, nelfinavir, efavirenz, or dexamethasone may decrease levels of caspofungin; caspofungin may decrease levels of tacrolimus; rifampin decreases caspofungin levels by 30% (ie, adjust dose to 70 mg/d)
Documented or suspected drug allergies or 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 moderate hepatic dysfunction (ie, decrease dose to 35 mg/d); may exacerbate preexisting renal dysfunction or myelosuppression
More on Coccidioidomycosis |
| Overview: Coccidioidomycosis |
| Differential Diagnoses & Workup: Coccidioidomycosis |
 Treatment & Medication: Coccidioidomycosis |
| Follow-up: Coccidioidomycosis |
| References |
| « Previous Page | Next Page » |
References
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Further Reading
Keywords
coccidioidomycosis, desert fever, Posadas-Wernicke disease, San Joaquin fever, San Joaquin Valley Fever, cocci fungal infection, Coccidioides immitis, CI, arthroconidia, extrapulmonary coccidioidomycosis disease, human immunodeficiency virus, HIV, acquired immunodeficiency syndrome, AIDS, certain lymphomas, posttransplant states, chronic steroid dependence, severe pulmonary infection, erythema nodosum, desert rheumatism, pneumonia, hemoptysis, pneumothorax, noncommunicating hydrocephalus, increased intracranial pressure, pericardial effusion, tamponade, osteomyelitis, septic arthritis, synovitis
