Medication Summary

The treatment of invasive aspergillosis and chronic necrotizing pulmonary aspergillosis (CNPA) requires intravenous antifungal therapy. Voriconazole is usually first-line therapy, sometimes in combination with other agents, such as caspofungin. Another triazole antifungal agent, isavuconazole, is also indicated for invasive aspergillosis. Amphotericin may sometimes be prescribed in treatment failures.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction treated with corticosteroids. The addition of oral antifungal therapy with itraconazole may be beneficial in the management of ABPA. Aspergillomas may respond to prolonged oral itraconazole therapy. Intracavitary therapy with amphotericin has also been used in small numbers of patients.

Further inpatient and outpatient medications

ABPA therapy includes oral prednisone and, in selected cases, oral itraconazole, usually for several months. As the patient is tapered off oral steroids, inhaled corticosteroids should be added for control of underlying asthma. The concomitant use of inhaled budesonide and oral itraconazole has been found to cause adrenal suppression in a significant proportion of patients with cystic fibrosis (CF) and ABPA.

For aspergilloma, oral itraconazole therapy may be beneficial. A Japanese study found that 60% of patients with aspergilloma had some response to oral itraconazole. In patients with bilateral aspergillomas or severe underlying disease preventing surgical resection, oral itraconazole therapy may be continued for several months.

For invasive aspergillosis and CNPA, specific antifungal therapy with oral or intravenous voriconazole is the usual initial therapy. Response to therapy may be poor. In patients who respond, prolonged therapy may be required.

Class Summary

Their mechanism of action may involve increasing the permeability of the cell membrane, which, in turn, causes intracellular components to leak.

Amphotericin B (Abelcet, AmBisome)

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Amphotericin B is a polyene antibiotic produced by a strain of Streptomyces nodosus. It can be fungistatic or fungicidal. It binds to sterols (eg, ergosterol) in the fungal cell membrane, causing intracellular components to leak, with subsequent fungal cell death. Newer lipid formulations are as effective as the original formulation and have less nephrotoxicity. Use may be associated with fever, rigors, and nausea (premedication with hydrocortisone and meperidine may be beneficial). Adequate hydration may decrease nephrotoxicity, and patients who can tolerate fluid should be administered prehydration and posthydration.

Itraconazole (Sporanox, Onmel, Tolsura)

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Itraconazole is a synthetic triazole antifungal agent with greater activity against Aspergillus than fluconazole or ketoconazole. It has fungistatic activity. Itraconazole slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

It is available in oral formulations (eg, capsule, suspension) and is useful for prolonged antifungal therapy. A new oral formulation of itraconazole is also available that uses SUBA (SUper-BioAvailable) technology to improve the bioavailability of poorly soluble drugs.

Caspofungin (Cancidas)

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Caspofungin is an antifungal with efficacy against A fumigatus,A flavus, and Aspergillus terreus. It is the first of a new class of antifungals called echinocandins. It works on a component of fungal cell walls that is not present in mammalian cells. Caspofungin is indicated for Aspergillus infection in patients who are refractory to or cannot tolerate other therapies. It has not been studied for primary therapy.

Voriconazole (VFEND)

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Voriconazole is used for primary treatment of invasive aspergillosis and salvage treatment of Fusarium species or Scedosporium apiospermum infections. It is a triazole antifungal agent that inhibits fungal cytochrome P-450–mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.

Posaconazole (Noxafil)

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Posaconazole is a triazole antifungal agent. It blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption. It is indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.

It is available as an oral suspension (200 mg/5 mL), 100-mg delayed-release tablet, and injection. Posaconazole injection is administered as a loading dose of 300 mg twice on the first day of treatment, followed by 300 mg once daily thereafter. The tablets are administered as a loading dose of 300 mg twice daily on day 1, followed by a once-daily maintenance dose of 300 mg.

Isavuconazonium sulfate (Cresemba)

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Isavuconazole is a triazole antifungal agent. Isavuconazole is the active moiety of the prodrug isavuconazonium sulfate. It is indicated for invasive aspergillosis and has activity against most strains of the following microorganisms, both in vitro and in clinical infection: Aspergillus flavus, Aspergillus fumigatus, and Aspergillus niger.

Class Summary

Corticosteroids are useful in the management of allergic reactions. These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Prednisone

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Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Questions

Samarakoon P, Soubani AO. Invasive pulmonary aspergillosis in patients with COPD: a report of five cases and systematic review of the literature. Chron Respir Dis. 2008. 5(1):19-27. [QxMD MEDLINE Link].
Ader F, Bienvenu AL, Rammaert B, Nseir S. Management of invasive aspergillosis in patients with COPD: rational use of voriconazole. Int J Chron Obstruct Pulmon Dis. 2009. 4(2):279-87. [QxMD MEDLINE Link]. [Full Text].
Desoubeaux G, Le-Bert C, Fravel V, Clauss T, Delaune AJ, Soto J, et al. Evaluation of a genus-specific ELISA and a commercial Aspergillus Western blot IgG® immunoblot kit for the diagnosis of aspergillosis in common bottlenose dolphins (Tursiops truncatus). Med Mycol. 2017 Dec 8. [QxMD MEDLINE Link].
Maertens J, Verhaegen J, Lagrou K, Van Eldere J, Boogaerts M. Screening for circulating galactomannan as a noninvasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients: a prospective validation. Blood. 2001 Mar 15. 97(6):1604-10. [QxMD MEDLINE Link].
Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis. 2006 May 15. 42(10):1417-27. [QxMD MEDLINE Link].
Kuhlman JE, Fishman EK, Siegelman SS. Invasive pulmonary aspergillosis in acute leukemia: characteristic findings on CT, the CT halo sign, and the role of CT in early diagnosis. Radiology. 1985 Dec. 157(3):611-4. [QxMD MEDLINE Link].
Kabbani D, Goldraich L, Ross H, Rotstein C, Husain S. Outbreak of invasive aspergillosis in heart transplant recipients: The role of screening computed tomography scans in asymptomatic patients and universal antifungal prophylaxis. Transpl Infect Dis. 2017 Nov 10. [QxMD MEDLINE Link].
Salez F, Brichet A, Desurmont S, Grosbois JM, Wallaert B, Tonnel AB. Effects of itraconazole therapy in allergic bronchopulmonary aspergillosis. Chest. 1999 Dec. 116(6):1665-8. [QxMD MEDLINE Link].
Stevens DA, Schwartz HJ, Lee JY, Moskovitz BL, Jerome DC, Catanzaro A, et al. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. N Engl J Med. 2000 Mar 16. 342(11):756-62. [QxMD MEDLINE Link].
Wark PA, Gibson PG, Wilson AJ. Azoles for allergic bronchopulmonary aspergillosis associated with asthma. Cochrane Database Syst Rev. 2003. (3):CD001108. [QxMD MEDLINE Link].
Wark PA, Hensley MJ, Saltos N, Boyle MJ, Toneguzzi RC, Epid GD, et al. Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: a randomized controlled trial. J Allergy Clin Immunol. 2003 May. 111(5):952-7. [QxMD MEDLINE Link].
Giron JM, Poey CG, Fajadet PP, Balagner GB, Assoun JA, Richardi GR, et al. Inoperable pulmonary aspergilloma: percutaneous CT-guided injection with glycerin and amphotericin B paste in 15 cases. Radiology. 1993 Sep. 188(3):825-7. [QxMD MEDLINE Link].
Mal H, Rullon I, Mellot F, Brugiere O, Sleiman C, Menu Y, et al. Immediate and long-term results of bronchial artery embolization for life-threatening hemoptysis. Chest. 1999 Apr. 115(4):996-1001. [QxMD MEDLINE Link].
Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002 Aug 8. 347(6):408-15. [QxMD MEDLINE Link].
Maertens J, Raad I, Petrikkos G, Boogaerts M, Selleslag D, Petersen FB, et al. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis. 2004 Dec 1. 39(11):1563-71. [QxMD MEDLINE Link].
Addrizzo-Harris DJ, Harkin TJ, McGuinness G, Naidich DP, Rom WN. Pulmonary aspergilloma and AIDS. A comparison of HIV-infected and HIV-negative individuals. Chest. 1997 Mar. 111(3):612-8. [QxMD MEDLINE Link].
Virnig C, Bush RK. Allergic bronchopulmonary aspergillosis: a US perspective. Curr Opin Pulm Med. 2007 Jan. 13(1):67-71. [QxMD MEDLINE Link].
Meersseman W, Vandecasteele SJ, Wilmer A, Verbeken E, Peetermans WE, Van Wijngaerden E. Invasive aspergillosis in critically ill patients without malignancy. Am J Respir Crit Care Med. 2004 Sep 15. 170(6):621-5. [QxMD MEDLINE Link].
Rutsaert L, Steinfort N, Van Hunsel T, Bomans P, Naesens R, Mertes H, et al. COVID-19-associated invasive pulmonary aspergillosis. Ann Intensive Care. 2020 Jun 1. 10 (1):71. [QxMD MEDLINE Link].
Bartoletti M, Pascale R, Cricca M, et al. Epidemiology of invasive pulmonary aspergillosis among COVID-19 intubated patients: a prospective study. Clin Infect Dis. 2020 Jul 28. [QxMD MEDLINE Link].
Helleberg M, Steensen M, Arendrup MC. Invasive aspergillosis in patients with severe COVID-19 pneumonia. Clin Microbiol Infect. 2020 Aug 5. [QxMD MEDLINE Link].
Mohamed A, Rogers TR, Talento AF. COVID-19 Associated Invasive Pulmonary Aspergillosis: Diagnostic and Therapeutic Challenges. J Fungi (Basel). 2020 Jul 22. 6 (3):[QxMD MEDLINE Link].
Lamoth F, Glampedakis E, Boillat-Blanco N, Oddo M, Pagani JL. Incidence of invasive pulmonary aspergillosis among critically ill COVID-19 patients. Clin Microbiol Infect. 2020 Jul 10. [QxMD MEDLINE Link].
Moeller B. Assessing Invasive Pulmonary Aspergillosis Incidence in COVID-19 vs Influenza. Pulmonary Advisor. Available at https://www.pulmonologyadvisor.com/home/topics/lung-infection/assessing-invasive-pulmonary-aspergillosis-incidence-in-covid-19-vs-influenza/. April 22, 2021; Accessed: May 12, 2021.
Lamoth F, Lewis RE, Walsh TJ, Kontoyiannis DP. Navigating the uncertainties of COVID-19 associated aspergillosis (CAPA): A comparison with influenza associated aspergillosis (IAPA). J Infect Dis. 2021 Mar 26. [QxMD MEDLINE Link].
Kaya S, Gençalioğlu E, Sönmez M, Köksal I. The importance of risk factors for the prediction of patients with invasive pulmonary aspergillosis. Rev Assoc Med Bras (1992). 2017 Sep. 63 (9):764-770. [QxMD MEDLINE Link].
Denning DW, Park S, Lass-Florl C, et al. High-frequency triazole resistance found In nonculturable Aspergillus fumigatus from lungs of patients with chronic fungal disease. Clin Infect Dis. 2011 May. 52(9):1123-9. [QxMD MEDLINE Link]. [Full Text].
Zhang X, Yang M, Hu J, Zhao H, Li L. Epidemiology of invasive pulmonary aspergillosis in patients with liver failure: Clinical presentation, risk factors, and outcomes. J Int Med Res. 2017 Jan 1. 300060517729907. [QxMD MEDLINE Link].
Smith NL, Denning DW. Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma. Eur Respir J. 2011 Apr. 37(4):865-72. [QxMD MEDLINE Link].
Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P, Judson MA, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis. 2003 Oct 1. 37 Suppl 3:S225-64. [QxMD MEDLINE Link].
Chai LY, Kullberg BJ, Johnson EM, Teerenstra S, Khin LW, Vonk AG, et al. Early Serum Galactomannan Trend as a Predictor of Outcome in Invasive Aspergillosis. J Clin Microbiol. 2012 May 2. [QxMD MEDLINE Link].
Becker MJ, Lugtenburg EJ, Cornelissen JJ, Van Der Schee C, Hoogsteden HC, De Marie S. Galactomannan detection in computerized tomography-based broncho-alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis. Br J Haematol. 2003 May. 121(3):448-57. [QxMD MEDLINE Link].
Guo YL, Chen YQ, Wang K, Qin SM, Wu C, Kong JL. Accuracy of BAL galactomannan in diagnosing invasive aspergillosis: a bivariate metaanalysis and systematic review. Chest. 2010 Oct. 138(4):817-24. [QxMD MEDLINE Link].
Luong ML, Clancy CJ, Vadnerkar A, et al. Comparison of an Aspergillus real-time polymerase chain reaction assay with galactomannan testing of bronchoalvelolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in lung transplant recipients. Clin Infect Dis. 2011 May. 52(10):1218-26. [QxMD MEDLINE Link].
Agarwal R. Allergic bronchopulmonary aspergillosis. Chest. 2009 Mar. 135(3):805-26. [QxMD MEDLINE Link].
Gruson D, Hilbert G, Valentino R, Vargas F, Chene G, Bebear C, et al. Utility of fiberoptic bronchoscopy in neutropenic patients admitted to the intensive care unit with pulmonary infiltrates. Crit Care Med. 2000 Jul. 28(7):2224-30. [QxMD MEDLINE Link].
Patterson R, Greenberger PA, Radin RC, Roberts M. Allergic bronchopulmonary aspergillosis: staging as an aid to management. Ann Intern Med. 1982 Mar. 96(3):286-91. [QxMD MEDLINE Link].
van der Ent CK, Hoekstra H, Rijkers GT. Successful treatment of allergic bronchopulmonary aspergillosis with recombinant anti-IgE antibody. Thorax. 2007 Mar. 62(3):276-7. [QxMD MEDLINE Link].
Krishnan-Natesan S, Chandrasekar PH. Current and future therapeutic options in the management of invasive aspergillosis. Drugs. 2008. 68(3):265-82. [QxMD MEDLINE Link].
Magill SS, Chiller TM, Warnock DW. Evolving strategies in the management of aspergillosis. Expert Opin Pharmacother. 2008 Feb. 9(2):193-209. [QxMD MEDLINE Link].
Kontoyiannis DP, Hachem R, Lewis RE, Rivero GA, Torres HA, Thornby J, et al. Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies. Cancer. 2003 Jul 15. 98(2):292-9. [QxMD MEDLINE Link].
Bedin Denardi L, Pantella Kunz de Jesus F, Keller JT, Weiblen C, de Azevedo MI, Oliveira V, et al. Evaluation of the efficacy of a posaconazole and anidulafungin combination in a murine model of pulmonary aspergillosis due to infection with Aspergillus fumigatus. Diagn Microbiol Infect Dis. 2018 Jan. 90 (1):40-43. [QxMD MEDLINE Link].
Brooks M. FDA Okays Antifungal Delayed-Release Tablets. Available at http://www.medscape.com/viewarticle/815030. Accessed: December 3, 2013.
Brooks M. FDA Clears IV Formulation of Antifungal Posaconazole. Medscape Medical News. Available at http://www.medscape.com/viewarticle/822125. Accessed: March 25, 2014.
National Institutes of Health. Isavuconazole (BAL8557) for primary treatment of invasive Aspergillosis.NLM identfier: NCT00412893. ClinicalTrials.gov. Available at http://clinicaltrials.gov/ct2/show/NCT00412893. Accessed: April 2, 2015.
Schubert MS, Goetz DW. Evaluation and treatment of allergic fungal sinusitis. I. Demographics and diagnosis. J Allergy Clin Immunol. 1998 Sep. 102(3):387-94. [QxMD MEDLINE Link].
Pidhorecky I, Urschel J, Anderson T. Resection of invasive pulmonary aspergillosis in immunocompromised patients. Ann Surg Oncol. 2000 May. 7(4):312-7. [QxMD MEDLINE Link].
Matthaiou DK, Dimopoulos G, Taccone FS, Bulpa P, Van den Abeele AM, Misset B, et al. Elderly versus nonelderly patients with invasive aspergillosis in the ICU: a comparison and risk factor analysis for mortality from the AspICU cohort. Med Mycol. 2017 Dec 8. [QxMD MEDLINE Link].
Maghrabi F, Denning DW. The Management of Chronic Pulmonary Aspergillosis: The UK National Aspergillosis Centre Approach. Curr Fungal Infect Rep. 2017. 11 (4):242-251. [QxMD MEDLINE Link].
Boyle BM, McCann SR. The use of itraconazole as prophylaxis against invasive fungal infection in blood and marrow transplant recipients. Transpl Infect Dis. 2000 Jun. 2(2):72-9. [QxMD MEDLINE Link].
Cordonnier C, Maury S, Pautas C, Bastie JN, Chehata S, Castaigne S, et al. Secondary antifungal prophylaxis with voriconazole to adhere to scheduled treatment in leukemic patients and stem cell transplant recipients. Bone Marrow Transplant. 2004 May. 33(9):943-8. [QxMD MEDLINE Link].
Kontoyiannis DP, Lionakis MS, Lewis RE, Chamilos G, Healy M, Perego C. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. J Infect Dis. 2005 Apr 15. 191(8):1350-60. [QxMD MEDLINE Link].
Wirk B, Wingard JR. Current approaches in antifungal prophylaxis in high risk hematologic malignancy and hematopoietic stem cell transplant patients. Mycopathologia. 2009 Dec. 168(6):299-311. [QxMD MEDLINE Link].
Mohammad RA, Klein KC. Inhaled amphotericin B for prophylaxis against invasive Aspergillus infections. Ann Pharmacother. 2006 Dec. 40(12):2148-54. [QxMD MEDLINE Link].
Avery RK. Aspergillosis in hematopoietic stem cell transplant recipients: risk factors, prophylaxis, and treatment. Curr Infect Dis Rep. 2009 May. 11(3):223-8. [QxMD MEDLINE Link].
Parry NM. New guidelines for the management of aspergillosis. Medscape Medical News. Available at http://www.medscape.com/viewarticle/865689. July 5, 2016; Accessed: August 15, 2016.
[Guideline] Patterson TF, Thompson GR 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Aug 15. 63 (4):e1-e60. [QxMD MEDLINE Link]. [Full Text].
Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018 Mar 12. [QxMD MEDLINE Link].

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Aspergillosis Medication

Medication Summary

Further inpatient and outpatient medications

Antifungal agents