AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Coccidioides immitis (CI), the etiologic agent responsible for coccidioidomycosis and the more well-known San Joaquin Valley Fever, is a dimorphic fungus, existing in both mold and a yeast form, endemic to the Southwestern United States and other lower Sonoran climates of Central America and South America. It was first described in the late 1800s; however, most cases at this time were consistent with more severe cases of C immitis infection, and many of the more benign cases were not recognized until 1929 with an unintentional exposure of a medical student at Stanford University. The medical student subsequently developed a respiratory tract infection and lived, thus sparking interest and the eventual connection between C immitis and Valley Fever.

Pathophysiology

C immitis infections occur when inhaled arthroconidia (spores) are deposited in the lower airways and subsequently change morphology to a spherule. These spherules enlarge, divide, and rupture to release hundreds of 2-5 micron spherule particles, which reproduce similarly. During primary infection, a mononuclear infiltrate may develop followed by subsequent conversion to PMN predominance.

Important in the development of effective immunity is the role of Th1-helper cells. Observational data and experimental models show that lack of Th1 or predominance of Th2 cells results in higher rates of disseminated disease (ie, in HIV/AIDS, certain lymphomas, transplant patients, chronically steroid dependent patients). C immitis infection can also occur by direct inoculation such as in contaminated penetrating objects. Other rare case reports have been documented such an infected lung transplant and sexually transmitted cases. It has also been theorized that some of the phagocytized arthroconidia are transported back to draining lymph nodes by macrophages and can cause a lymphangitis. It is generally accepted that the inoculating dose responsible for infection is small and may be 10 or less arthroconidia.

Frequency

United States

C immitis infection rates are typically quoted in the 100,000 per year range within the United States. Peak incidence occurs during the summer to early fall months and is related to the variations in weather and spore formation. In particular, outbreaks have been documented during earthquakes and wind storms, which agitate arthroconidia causing them to become airborne.

Historically, people at greatest risk for contact are farmers, construction workers, and archaeologists. In fact, in recent time, the Northridge earthquake and outbreaks among archaeologists highlight these events. Thus, otherwise healthy persons exposed to high spore burdens have a higher likelihood of more severe disease. C immitis cases are by no means confined to the southwestern United States, and, in fact, cases have been reported in travelers visiting endemic areas. This illustrates the need for careful history taking and possible exposure in endemic areas.

International

Affected areas are in the lower Sonoran areas, which are characterized by semiarid climates with hot summers and alkaline soil. These areas include northern Mexico, Central America, and South America.

Mortality/Morbidity

C immitis infection is rarely fatal except in those who may be extremely immunocompromised. Five to 10 percent of patients will harbor residual pulmonary disease, and only about 1% of patients progress to have disseminated CI disease.

Any person with impaired cellular immunity has a greater risk for disseminated CI disease. HIV/AIDS patients are particularly susceptible to more severe CI disease, especially at CD4 counts less than 250. Also there is an increased risk of dissemination during pregnancy, with each trimester at slightly higher risk. Patients with lymphoma, those with solid organ transplantation, and patients on long-term corticosteroid treatment are also at higher risk of dissemination. Recent advances in immunosuppressive therapy with TNF-alpha inhibitors have also been proposed as a risk factor for advanced or disseminated disease.

Race

Filipinos, blacks, and Hispanics have an increased risk of disseminated disease as compared with Caucasians. Studies have shown that genotypic variations in HLA either confer increased or reduced risk of dissemination. Hispanics with A or B type blood groups are also at slightly higher risk for advanced and/or disseminated disease when compared with the population as a whole.

• Low income has been associated with a predisposition for severe pulmonary infection and disseminated disease. Although it is unclear what role health care access has in this observation.

Sex

Incidence is equal in males and females.

Age

All age groups can be affected.

• Congenital infection is rarely a factor in childhood coccidioidomycosis. In disseminated disease, the mortality rates in neonates and infants are much higher than those in children, adolescents, and adults.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The natural history of C immitis infection is usually one of a self-limited respiratory tract infection, which occurs 1-3 weeks after exposure. Most cases (60%) are subclinical, never reaching the attention of a physician.

Common complaints of those cases making it to clinical attention are nonspecific and consist of fever, cough, chest pain, fatigue, dyspnea, headache, arthralgias, and/or myalgias. Skin manifestations are also seen in a small percentage of cases. In addition to the above clinical scenarios, CI can progress to a variety of presentations. The triad of fever, erythema nodosum, and arthralgias is commonly referred to as San Joaquin Valley Fever or desert rheumatism.

Primary pulmonary infection may progress to overt pneumonia, chronic lung infections, hematogenous spread, disseminated disease, and meningitis. Important in the diagnosis of CI is clinical suspicion and eliciting a history of possible exposure or travel to an endemic area.

Physical

• Pulmonary
• • In addition to the asymptomatic infection and benign/unrecognized respiratory infections, CI can also go on to a progressive disease forming pneumonias of varying degree. Infiltrates can range from segmental or lobar pneumonias to diffuse reticulonodular infiltrates, but it can also progress to complete respiratory failure.
  • A small percentage of patients may present with asymptomatic pulmonary nodules, which may be confused with malignancy. Nodules, although asymptomatic, may persist over time and can degenerate into thin-walled cavitations, which may erode into adjacent small airways resulting in hemoptysis or pneumothorax.
  • Chronic pulmonary patterns may also develop including chronic fibrocavitary lesions.
  • Physical examination findings are generally nonspecific but can include rales, pleural rubs, wheezing, and decreased breath sounds from effusions.
• Dermatologic
• • A variety of dermatologic sequelae can result from CI infection. The best known of these is erythema nodosum, which presents as tender, erythematous nodules on the anterior lower extremities. These nodules are immune complexes consistent with immune complex phenomena.
  • Disseminated infection can also result in ulceration and fistulas from underlying infection. Lesions can also present as ulcerations or verrucous lesions with a predilection for the nasolabial area.
• CNS
• • As in other organ systems, CI can present in a variety of ways and CNS is no exception. The most serious form of disseminated CI is meningitis. As with other etiologies of meningitis, symptoms typically include fever, headache, meningismus, nausea, vomiting, and altered mental status.
  • Basilar meninges are often affected, and inflammation may result in a noncommunicating hydrocephalus, increased ICP, and subsequent death if left untreated. Cranial nerve palsies, abscesses, and vasculitides are also described complications of CNS infection.
• Cardiovascular
• • Cardiovascular complications of CI are rare and account for an extremely small percentage of clinical presentations. However, when they do occur they can be devastating.
  • Pericardial effusions are a rare but recognized occurrence in CI, and they can produce cardiovascular compromise and tamponade in extreme cases.
• Musculoskeletal
• • The most common manifestations of CI with respect to the musculoskeletal system are osteomyelitis, septic arthritis, and synovitis. The latter two often need to be differentiated clinically.
  • Arthritis is usually monoarticular, but it can be migratory in nature. Typically, the weightbearing joints, such as the knee, are affected. Arthrocentesis samples typically show an exudative effusion. Presence of organisms varies, and literature shows that typically direct visualization of organisms is rare but can occur in up to half of cases.
  • Although osteomyelitis can occur from direct inoculation of bone from contaminated penetrating objects, it is more commonly a result of hematogenous spread and disproportionately affects the vertebra, and paraspinal abscesses are a possible complication. Other common sites of involvement include the tibia, femur, skull, and bones of the hands and feet. Lesions in the larger bones typically appear as radiopaque lesions, whereas smaller bones tend to have an appearance more typical ofosteomyelitis.
• Disseminated CI
• • CI can virtually present in any organ system. In addition to the above, patients with disseminated CI may present in septic shock.

Causes

Coccidioides immitis, a soil fungus particularly adapted to arid conditions, causes coccidioidomycosis.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Histoplasmosis
Blastomycosis
Paracoccidioidomycosis
Other fungi
Lung abscess
Lymphoma
Other causes of cough, fever, and fatigue
Old granuloma

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Guide diagnostic evaluation by index of suspicion and patient's clinical presentation. A variety of testing may aid or confirm the diagnosis.
• • CBC may reveal a leukocytosis with a eosinophilia, lymphocytosis, or monocytosis.
  • Direct observation: Observe for direct evidence of spherules of C immitis from various aspirates/body fluids or biopsies. Various fungal stains may increase sensitivity.
  • Skin testing: Delayed-type hypersensitivity reactions may become positive as early as 1-3 weeks. Although reactivity may endure for a lifetime, it may wane in some individuals particularly those who may be anergic.
  • Serology tube precipitin assays for IgM may detect acute infection. IgM reactivity usually does not persist for more than 6 months. Complement fixation is useful in detecting IgG immunity and is particularly useful in evaluating the extent and response to meningeal disease.
  • Culture may be performed, but results are usually delayed given a 5- to 7-day incubation.
  • Immunoprecipitant assays
  • Immunodiffusion

Imaging Studies

• Chest x-ray should be done routinely to check for signs of pulmonary infection.
• • May be normal
  • Infiltrates
  • Nodules
  • Cavity
  • Mediastinal or hilar adenopathy
  • Pleural effusion
• Radiographs of affected areas of the body are done to check for osteomyelitis.

Procedures

• If unable to obtain a diagnosis by skin testing or serology, consider performing the following:
• • Bronchoscopy
  • Fine-needle biopsy
  • Open-lung biopsy
  • Pleural biopsy
  • Bone/skin/node biopsy

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Emergency Department Care

Rarely is therapy started in ED, but infectious disease consultants often expedite therapy in endemic areas. Therapies include amphotericin B and the azoles, including ketoconazole and fluconazole.

Consultations

Report cases to infectious disease and local health departments.

• Consult pulmonology.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

In general, severity and tempo of disease usually dictates tempo of treatment. In patients with suspected or documented uncomplicated primary CI, treatment opinion varies from careful observation to treatment with 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 exist on which uncomplicated infections need treatment. However, at risk groups for dissemination such as blacks, Filipinos, HIV/AIDS patients, DM, and third trimester pregnancies warrant more aggressive treatment. Typically, this may be accomplished with fluconazole except in pregnant women, as azole antifungals are teratogenic. Pregnant women with suspected CI infection may be treated with amphotericin B. To date, few RCTs have looked specifically at the efficacy of the different azoles for treatment of CI. Of note, Galgiani et al compared fluconazole and itraconazole in a RCT for treatment of CI. Although no statistically significant difference was noted, there was a trend in the better outcomes in musculoskeletal CI with itraconazole.

Patients with more advanced disease require more aggressive treatment. In particular, patients exhibiting signs of meningitis need either IV antibiotic therapy with amphotericin unless otherwise contraindicated or high-dose azole therapy with or without intrathecal amphotericin. Some recent case reports have suggested that voriconazole or posaconazole may be therapeutic options in these patients, although these are only anecdotal to date, and no comparative studies have been performed. The role of caspofungin in combination with fluconazole has recently been cited as beneficial in a case report of a Korean gentleman with CI pneumonia. Steroids may be of some benefit in patients with vasculitis.

Drug Category: Antifungal agents

Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Drug Name	Fluconazole (Diflucan)
Description	Synthetic bistriazole antifungal agent; highly selective inhibitor of fungal cytochrome P-450 and sterol C-14 alpha-demethylation with broad-spectrum activity.
Adult Dose	200-400 mg PO qd
Pediatric Dose	3-6 mg/kg PO qd for 14-28 d depending on severity of infection
Contraindications	Documented hypersensitivity
Interactions	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
Pregnancy	C - Safety for use during pregnancy has not been established.
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

Drug Name	Ketoconazole (Nizoral)
Description	Imidazole broad-spectrum antifungal agent. Impairs synthesis of ergosterol, allowing increased permeability and leakage of cellular components.
Adult Dose	200-400 mg PO qd
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; fungal meningitis
Interactions	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
Pregnancy	C - Safety for use during pregnancy has not been established.
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)

Drug Name	Itraconazole (Sporanox)
Description	Triazole analogue of ketoconazole
Adult Dose	400-600 mg PO qd
Pediatric Dose	Specific dosing in children with CI not studied; in other antifungal regimen recommend dose is 5 mg/kg/d PO divided qd/bid; max dose 10 mg/kg/d
Contraindications	Documented or suspected drug allergies or hypersensitivity; CHF or liver dysfunction
Interactions	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)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Use cautiously in patients with hepatic insufficiency

Drug Name	Voriconazole (Vfend)
Description	Triazole antifungal agent that inhibits fungal cytochrome P450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.
Adult Dose	200 mg PO bid or 3-6 mg/kg IV q12h
Pediatric Dose	Not established
Contraindications	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
Interactions	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)
Pregnancy	D - Unsafe in pregnancy
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

Drug Name	Posaconazole (Noxafil)
Description	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 oral susp (200 mg/5 mL). Indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.
Adult Dose	200 mg (5 mL) PO tid with food or liquid nutritional supplement to enhance absorption
Pediatric Dose	<13 years: Not established >13 years: Administer as in adults
Contraindications	Documented hypersensitivity; coadministration with ergot alkaloids; coadministration with CYP3A4 substrates likely to result in serious toxicities (eg, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine)
Interactions	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)
Pregnancy	C - Safety for use during pregnancy has not been established.
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

Drug Name	Caspofungin (Cancidas)
Description	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 Dose	Not established; typical antifungal regimens suggest starting at 70 mg IV on day 1 followed by 50 mg IV qd
Pediatric Dose	Not established
Contraindications	Documented or suspected drug allergies or hypersensitivity
Interactions	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)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in moderate hepatic dysfunction (ie, decrease dose to 35 mg/d); may exacerbate preexisting renal dysfunction or myelosuppression

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Indications for admission
• • Immunocompromised conditions
  • Dissemination
  • Any need for symptomatic support or intravenous therapy

Complications

• Severe cases are fatal, particularly if associated with meningitis.
• Obstruction of pulmonary tissue due to scarring or cavities may occur.

Prognosis

• Most cases are self-limited and resolve within a few months.
• Prognosis is poor if the patient has a weak cell-mediated immunity or high IgG.
• Relapse of extrapulmonary or disseminated disease is common.

Patient Education

• Educate populations at high risk (eg, immunocompromised, pregnant women, African Americans, Filipinos, those with diabetes) on avoidance of high-risk activities (eg, construction, archeological digs).

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to consider this or other fungal infections in patients in whom other therapies have failed and in those who appear to have a chronic illness or are resident of (or traveler to) endemic regions
• In recent times, CI has regained interest due to its potential as a bioterrorism weapon. CI is listed in some texts as a potential agent for biological warfare. Although the exact outcome of a CI attack cannot be known, CI possesses some properties that could make it attractive as a weapon. In particular, CI spores can be disseminated and aerosolized rather easily. However, the infectivity in this capacity is unknown and effects probably are limited.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Ampel NM. Combating opportunistic infections: coccidioidomycosis. Expert Opin Pharmacother. Feb 2004;5(2):255-61.
• Anstead GM, Corcoran G, Lewis J. Refractory coccidioidomycosis treated with posaconazole. Clin Infect Dis. Jun 15 2005;40(12):1770-6. [Medline].
• Bergstrom L, Yocum DE, Ampel NM. Increased risk of coccidioidomycosis in patients treated with tumor necrosis factor alpha antagonists. Arthritis Rheum. Jun 2004;50(6):1959-66. [Medline].
• Blair JE, Smilack JD, Caples SM. Coccidioidomycosis in patients with hematologic malignancies. Arch Intern Med. Jan 10 2005;165(1):113-7. [Medline].
• CDC. Increase in coccidioidomycosis--Arizona, 1998-2001. MMWR Morb Mortal Wkly Rep. Feb 14 2003;52(6):109-12. [Medline].
• CDC. From the Centers for Disease Control and Prevention. Coccidioidomycosis following the Northridge earthquake--California, 1994. JAMA. Jun 8 1994;271(22):1735. [Medline].
• Catanzaro A. Coccidioidomycosis. In: Manual of Clinical Problems in Pulmonary Medicine. 5th ed. Lippincott Williams & Wilkins;2000.
• Comrie AC. Climate factors influencing coccidioidomycosis seasonality and outbreaks. Environ Health Perspect. Jun 2005;113(6):688-92. [Medline].
• Deresinski S. Coccidioides immitis as a potential bioweapon. Semin Respir Infect. Sep 2003;18(3):216-9. [Medline].
• Deresinski SC, Mirels LF, Kemper CA. Coccidioides immitis. In: Infectious Diseases. Philadelphia: Lippincott Williams & Wilkins;2004:2227-46.
• Galgiani J. Coccidioides immitis. In: Principles and Practice of Infectious Diseases. New York: Churchill Livingstone;2000:2746-57.
• Galgiani JN, Catanzaro A, Cloud GA. Comparison of oral fluconazole and itraconazole for progressive, nonmeningeal coccidioidomycosis. A randomized, double-blind trial. Mycoses Study Group. Ann Intern Med. Nov 7 2000;133(9):676-86. [Medline].
• Jones JL, Fleming PL, Ciesielski CA. Coccidioidomycosis among persons with AIDS in the United States. J Infect Dis. Apr 1995;171(4):961-6. [Medline].
• Louie L, Ng S, Hajjeh R. Influence of host genetics on the severity of coccidioidomycosis. Emerg Infect Dis. Sep-Oct 1999;5(5):672-80. [Medline].
• Park DW, Sohn JW, Cheong HJ. Combination therapy of disseminated coccidioidomycosis with caspofungin and fluconazole. BMC Infect Dis. 2006;6:26. [Medline].
• Prabhu RM, Bonnell M, Currier BL. Successful treatment of disseminated nonmeningeal coccidioidomycosis with voriconazole. Clin Infect Dis. Oct 1 2004;39(7):e74-7. [Medline].
• Rosenstein NE, Emery KW, Werner SB. Risk factors for severe pulmonary and disseminated coccidioidomycosis: Kern County, California, 1995-1996. Clin Infect Dis. Mar 1 2001;32(5):708-15. [Medline].
• Schneider E, Hajjeh RA, Spiegel RA. A coccidioidomycosis outbreak following the Northridge, Calif, earthquake. JAMA. Mar 19 1997;277(11):904-8. [Medline].

Article Last Updated: Sep 28, 2006