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Pediatric Aspergillosis Medication

  • Author: Vandana Batra, MD; Chief Editor: Russell W Steele, MD  more...
 
Updated: Aug 16, 2016
 

Medication Summary

Voriconazole is now the drug of choice for the treatment of invasive aspergillosis (IA). Although disease outcomes substantially improve with antifungal treatment, patient survival and infection resolution depend on improved immunosuppression. Response rates are low if the patient remains neutropenic. Voriconazole has shown a good outcome in 34% of patients with cerebral aspergillosis, which was previously associated with a high mortality. Caspofungin is an echinocandin that is primarily used as a salvage drug either alone or in combination with amphotericin B lipid preparations.

Amphotericin B has a broad antifungal spectrum but has limited use in view of significant nephrotoxicity and dose-limiting side effects. Various amphotericin B lipid preparations are available to help reduce nephrotoxicity. Lipid preparations of amphotericin B (ABLC, Abelcet) are approved by the FDA to treat invasive fungal infections in patients who are intolerant or refractory to conventional amphotericin (ie, deoxycholate). Amphotericin B cholesteryl sulfate complex (Amphotec) and the liposomal formulation of amphotericin B (AmBisome) have received FDA approval for the treatment of invasive aspergillosis in patients who cannot tolerate or who fail to respond to conventional amphotericin B deoxycholate. These lipid formulations are picked up preferentially by the reticuloendothelial system and are broken down by lipases locally at the site of infection.[16]

Caspofungin and voriconazole combinations have also shown to be successful as salvage drug therapy for invasive aspergillosis. Posaconazole is a new triazole that was recently approved by the FDA. Itraconazole has a status of a prophylaxis drug and is used in neutropenic patients in several centers. Steroid administration is the mainstay treatment for allergic bronchopulmonary aspergillosis (ABPA).

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Antifungal agents

Class Summary

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.

The azole group of drugs, including voriconazole, inhibit the cytochrome P450 (CYP)-dependent enzyme, 14-a-demethylase, which leads to the accumulation of toxic sterol precursors. Echinocandins (eg, caspofungin) inhibit synthesis of beta-(1,3)-D-glucan, an essential component of fungal cell wall.

Voriconazole (VFEND)

 

Used for primary treatment of invasive aspergillosis and salvage treatment of Fusarium species or Scedosporium apiospermum infections. A triazole antifungal agent that inhibits fungal CYP450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.

Amphotericin B (Amphocin, Fungizone)

 

Polyene antibiotic produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols in the fungal cell membrane, such as ergosterol, causing intracellular components to leak and the subsequent death of fungal cell.

Amphotericin B lipid complex (Abelcet) - - Amphotericin B liposome (AmBisome)

 

FDA approved to treat invasive fungal infections in patients who are intolerant to or refractory to conventional amphotericin therapy.

Itraconazole (Sporanox)

 

Fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP450–dependent synthesis of ergosterol. Used alone as an alternative treatment for nonmeningeal cases and for patients who are intolerant of or whose infections are refractory to amphotericin B therapy.

Caspofungin (Cancidas)

 

Used to treat refractory invasive aspergillosis. 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.

Posaconazole (Noxafil)

 

Triazole antifungal agent. 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 due to severe immunosuppression.

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Corticosteroids

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. These agents also modify the body's immune response to diverse stimuli.

Prednisone (Deltasone, Orasone, Meticorten, Sterapred)

 

Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

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Contributor Information and Disclosures
Author

Vandana Batra, MD Fellow, Department of Pediatric Hematology Oncology, Children's Hospital of Philadelphia

Vandana Batra, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Coauthor(s)

Jocelyn Y Ang, MD, FAAP, FIDSA Associate Professor, Department of Pediatrics, Wayne State University School of Medicine; Consulting Staff, Division of Infectious Diseases, Children's Hospital of Michigan

Jocelyn Y Ang, MD, FAAP, FIDSA is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Basim Asmar, MD Director, Department of Pediatrics, Division of Infectious Diseases, Children's Hospital of Michigan; Professor, Department of Pediatrics, Wayne State University School of Medicine

Basim Asmar, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Mark R Schleiss, MD Minnesota American Legion and Auxiliary Heart Research Foundation 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, Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

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, Southern Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

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 Medical Association, American Society for Microbiology, 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 Experimental Biology and Medicine, Society for Pediatric Research, Southern Medical Association, Society for Ear, Nose and Throat Advances in Children, American Federation for Clinical Research, Surgical Infection Society, Armed Forces Infectious Diseases Society

Disclosure: Nothing to disclose.

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