Coccidioidomycosis Medication

  • Author: Duane R Hospenthal, MD, PhD; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Dec 8, 2011
 

Medication Summary

In general, the severity and tempo of coccidioidomycosis dictates the approach to 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.

Historically, amphotericin B has been the drug of choice to treat disseminated coccidioidomycosis. Oral azoles have provided a desirable alternative for both initial therapy and completion of courses after amphotericin therapy. The benefits of azoles include oral formulations and fewer adverse effects.

Azole antifungals are not used in pregnant women because these agents are teratogenic. Pregnant women may be treated with amphotericin B.

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. Steroids may be somewhat beneficial in patients with vasculitis.

Effective antifungal therapy can be given in an outpatient or inpatient setting. The initial use of amphotericin may require an inpatient stay, and long-term amphotericin therapy requires placement of an indwelling intravenous catheter, such as a peripherally inserted central catheter (PICC) line.

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Antifungals

Class Summary

Antifungal agents preferentially bind to the primary fungal cell membrane sterol (ergosterol). Amphotericin B increases the permeability of the cell membrane, which in turn causes intracellular components to leak. Azoles interfere with an enzyme in the sterol biosynthesis pathway production of cell membrane ergosterol. Echinocandins block fungal cell wall synthesis by inhibiting 1,3-beta glucan synthase.

Amphotericin B

 

Amphotericin B is the drug of choice for rapidly progressing coccidioidal infection and disease nonresponsive to oral azole therapy. It is administered IV or intrathecally. Intrathecal amphotericin B has been used for coccidioidal meningitis.

Amphotericin B is a polyene antifungal agent produced by a strain of Streptomyces nodosus. Depending on the concentration attained in body fluids and on fungal susceptibility, this agent can be fungistatic or fungicidal. It binds to sterols (eg, ergosterol) in the fungal cell membrane, causing intracellular components to leak, with subsequent cell death. Metabolic clearance is prolonged and not affected by renal or hepatic insufficiency.

Three lipid formulations (Ambisome, Abelcet, Amphotec) promising for reducing toxicity are currently licensed for use when amphotericin B fails or is unacceptably toxic. There is a significant reduction in nephrotoxicity and infusion-related reactions with continuous 24-h infusion vs conventional 2-h to 6-h infusion.

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Fluconazole (Diflucan)

 

Fluconazole is a synthetic triazole antifungal (broad-spectrum bistriazole) that selectively inhibits fungal CYP450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol. It is used to treat mild-to-moderate infections or severe or life-threatening infections in patients intolerant of amphotericin B. It may be used for maintenance after course of amphotericin B in coccidioidal meningitis. It penetrates CSF well. Metabolic clearance is prolonged in renal dysfunction.

Fluconazole is preferred over ketoconazole because of better response rates and less GI and endocrine adverse effects. It is available as an oral suspension.

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Ketoconazole

 

Ketoconazole is an imidazole broad-spectrum antifungal agent that inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.

This agent has been used in treatment of coccidioidomycosis, although fluconazole and itraconazole are preferred because of low response rates (< 40%) with ketoconazole. In addition, it may have greater GI and endocrine adverse effects at high doses.

Administer ketoconazole orally for mild-to-moderate infections that warrant treatment. It penetrates CSF poorly, but in unusual cases is used to treat coccidioidal meningitis.

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Itraconazole (Sporanox)

 

A triazole analogue of ketoconazole, itraconazole is preferred to its parent compound because of enhanced safety and efficacy. It is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP450-dependent synthesis of ergosterol, a vital component of fungal cell membranes. It is used for mild-to-moderate infections that warrant treatment. Despite poor CSF penetration, it is successfully used to treat coccidioidal meningitis.

An IV form is available, but long-term usage is not established. Itraconazole is also available in an oral solution, which provides better, more consistent absorption than the capsule. Take capsules with full meal to improve absorption, but take oral solution on empty stomach, if possible.

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Voriconazole (Vfend)

 

Voriconazole is a triazole antifungal agent that inhibits fungal CYP450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis. Case reports describe efficacy in disseminated disease or meningitis refractory to first-line agents.

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Posaconazole (Noxafil)

 

Posaconazole is a triazole antifungal agent that possesses structural similarities to itraconazole. It blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption.

Posaconazole is available as an oral suspension (200 mg/5 mL). It is indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.

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Caspofungin (Cancidas)

 

Caspofungin is the first of a new class of antifungal drugs (glucan synthesis inhibitors). It inhibits synthesis of beta-(1,3)-D-glucan, an essential component of fungal cell wall. It is used to treat refractory invasive aspergillosis.

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Contributor Information and Disclosures
Author

Duane R Hospenthal, MD, PhD  Professor of Medicine, Uniformed Services University of the Health Sciences; Physician, Infectious Disease Service, San Antonio Military Medical Center (formerly Brooke Army Medical Center)

Duane R Hospenthal, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Armed Forces Infectious Diseases Society, Association of Military Surgeons of the US, Infectious Diseases Society of America, International Society for Human and Animal Mycology, International Society for Infectious Diseases, International Society of Travel Medicine, and Medical Mycology Society of the Americas

Disclosure: Nothing to disclose.

Coauthor(s)

Kelley Struble, DO  Fellow, Department of Infectious Diseases, University of Oklahoma College of Medicine

Disclosure: Nothing to disclose.

Ana Paula Oppenheimer, MD, MPH  Fellow, Section of Infectious Diseases, Wake Forest University Baptist Medical Center

Disclosure: Nothing to disclose.

Edward L Arsura, MD  Chair, Department of Medicine, Chief Medical Officer, Richmond University Medical Center

Edward L Arsura, MD is a member of the following medical societies: American College of Physician Executives, American College of Physicians, American Federation for Medical Research, American Heart Association, American Medical Association, California Medical Association, Society of General Internal Medicine, and Southern Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Itzhak Brook, MD, MSc Professor, Department of Pediatrics, Georgetown University School of Medicine

Itzhak Brook, MD, MSc is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Armed Forces Infectious Diseases Society, Association of Military Surgeons of the US, Infectious Diseases Society of America, International Immunocompromised Host Society, International Society for Infectious Diseases,Medical Society of the District of Columbia, New York Academy of Sciences, Pediatric Infectious Diseases Society, Society for Ear, Nose and Throat Advances in Children, Society for Experimental Biology and Medicine, Society for Pediatric Research, Southern Medical Association, and Surgical Infection Society

Disclosure: Nothing to disclose.

David FM Brown, MD Associate Professor, Division of Emergency Medicine, Harvard Medical School; Vice Chair, Department of Emergency Medicine, Massachusetts General Hospital

David FM Brown, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Archana Chatterjee, MD, PhD Professor of Pediatrics, Medical Microbiology and Immunology, and Pharmacy, Division of Pediatric Infectious Diseases, Chief of Division of Pediatric Infectious Diseases, Creighton University School of Medicine; Hospital Epidemiologist and Medical Director of Infection Control, Children's Hospital

Archana Chatterjee, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, International Society for Infectious Diseases, Pediatric Infectious Diseases Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Michele M Cheung, MD Consulting Staff, Department of Pediatrics, Division of Pediatric Infectious Diseases, University of California, San Francisco, School of Medicine

Michele M Cheung, MD is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

John E Cho, MD Staff Physician, Providence Tarzana Medical Center

John E Cho, MD is a member of the following medical societies: American College of Chest Physicians, California Medical Association, and Phi Beta Kappa

Disclosure: Nothing to disclose.

James de la Torre, MD Resident Physician, Department of Emergency Medicine, LAC+USC Medical Center

Disclosure: Nothing to disclose.

Thomas E Herchline, MD Professor of Medicine, Wright State University, Boonshoft School of Medicine; Medical Director, Public Health, Dayton and Montgomery County, Ohio

Thomas E Herchline, MD is a member of the following medical societies: Alpha Omega Alpha, Infectious Diseases Society of America, and Infectious Diseases Society of Ohio

Disclosure: Nothing to disclose.

Thomas M Kerkering, MD Chief of Infectious Diseases, Virginia Tech Carilion School of Medicine

Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Joseph Kim, MD Chairman, Department of Emergency Medicine, Western Medical Center; Clinical Instructor, University of California, Irvine, School of Medicine

Disclosure: Nothing to disclose.

Zab Mosenifar, MD Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Professor and Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society

Disclosure: Nothing to disclose.

Catherine O'Keefe, DNP, APRN Assistant Professor of Nursing and Pediatric Nurse Practitioner, Pediatric Infectious Diseases, Creighton University Medical Center

Catherine O'Keefe, DNP, APRN is a member of the following medical societies: American Academy of Nurse Practitioners, National Association of Pediatric Nurse Practitioners, and Nebraska Nurse Practitioners

Disclosure: Nothing to disclose.

Michael Peterson, MD Chief of Medicine, Vice-Chair of Medicine, University of California, San Francisco, School of Medicine; Endowed Professor of Medicine, University of California, San Francisco-Fresno, School of Medicine

Michael Peterson, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Allison J Richard, MD Assistant Professor of Emergency Medicine, Keck School of Medicine of the University of Southern California; Associate Director, Division of International Medicine, Attending Physician, Department of Emergency Medicine, LAC+USC Medical Center

Disclosure: Nothing to disclose.

Mark R Schleiss, MD American Legion Chair of Pediatrics, Professor of Pediatrics, Division Director, Division of Infectious Diseases and Immunology, Department of Pediatrics, University of Minnesota Medical School

Mark R Schleiss, MD is a member of the following medical societies: American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Sat Sharma, MD, FRCPC Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital

Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association

Disclosure: Nothing to disclose.

Barry J Sheridan, DO Chief Warrior in Transition Services, Brooke Army Medical Center

Barry J Sheridan, DO is a member of the following medical societies: American Academy of Emergency Medicine

Disclosure: Nothing to disclose.

Guy W Soo Hoo, MD, MPH Clinical Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; Director, Medical Intensive Care Unit, Pulmonary and Critical Care Section, West Los Angeles Healthcare Center, Veteran Affairs Greater Los Angeles Healthcare System

Guy W Soo Hoo, MD, MPH is a member of the following medical societies: American Association for Respiratory Care, American College of Chest Physicians, American College of Physicians, American Thoracic Society, California Thoracic Society, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Peggy Weintrub, MD Chief, Division of Pediatric Infectious Diseases, Clinical Professor, Department of Pediatrics, University of California, San Francisco, School of Medicine

Peggy Weintrub, MD is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

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Soft tissue abscess due to cocci.
Pulmonary cocci spherule (Hematoxylin-eosin stain).
Pulmonary cocci spherule, periodic acid-Schiff stain.
Erythema nodosum can be observed in coccidioidomycosis, tuberculosis, histoplasmosis, drug reactions, and streptococcal infections.
A Coccidioides immitis spherule containing daughter cysts. Courtesy of Thomas Matthew.
Arthroconidia become airborne and infect the human host to begin the parasitic phase of its life cycle. The arthroconidia develop into spherules containing endospores, which propagate infection in human tissues. Courtesy of Thomas Matthew.
A granuloma with coccidioides immitis spherule (pretracheal lymph node biopsy).
A ruptured Coccidioides immitis spherule (pretracheal lymph node biopsy).
Gomori methenamine silver stain of Coccidioides immitis spherule (pretracheal lymph node biopsy).
Periodic acid-Schiff stain of Coccidioides immitis spherule (pretracheal lymph node biopsy).
Coccidioidal spherules rupturing and releasing endospores. Gomori methenamine silver (GMS) stain. Photograph by Joseph Rabban, MD.
 
 
 
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