Pulmonary fungal disease ( including aspergillosis ) in the Immunocompetent adult - Diagnosis and Treatment of
|Publication: 30/09/2012 --|
|Last review: 07/02/2020|
|Next review: 07/02/2023|
|Approved By: Improving Antimicrobial Prescribing Group|
|Copyright© Leeds Teaching Hospitals NHS Trust 2020|
This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
Diagnosis and Treatment of Pulmonary fungal disease (including aspergillosis) in the Immunocompetent adult
Pulmonary fungal disease ( including aspergillosis ) in the Immunocompetent adult
This guideline applies to adult non-neutropenic patients with pulmonary fungal disease (for immunocompromised patients see Guidelines for the use of Antifungal Treatments in Adult Haematology Patients). These people are typically seen in respiratory medicine as out- or in-patients. This guideline excludes people with cystic fibrosis (CF, see Diagnosis and Treatment of Allergic Bronchopulmonary Aspergillosis (ABPA) and Aspergillus bronchitis in Children and Adults with Cystic Fibrosis). This guideline relates almost entirely to Aspergillus disease, but also includes a condition SAFS (see below), which may also be caused by other fungi.
Allergic bronchopulmonary aspergillosis (ABPA).
ABPA occurs in people with a background of atopy and asthma. Diagnostic features include a high total IgE, specific IgE to Aspergillus and positive serum IgG to Aspergillus. CT imaging of the thorax may demonstrate central bronchiectasis. Treatment of ABPA is with corticosteroids and antifungal therapy.
Severe asthma with fungal sensitization (SAFS)
SAFS occurs in people with severe asthma. They have elevated total IgE levels and evidence of IgE sensitivity to Aspergillus or other moulds. Treatment is mainly with corticosteroids and antifungal therapy.
Sub-acute invasive aspergillosis (SAIA) and chronic pulmonary aspergillosis (CPA)
People with chronic obstructive pulmonary disease, other lung diseases or receiving long-term corticosteroid therapy may present acutely with lower respiratory tract infection due to Aspergillus. Other patients may present with a more chronically developing disease. Typical presentation is with dyspnoea, reduction in lung function and failure to respond to antibiotic therapy. This diagnosis may be indicated by sputum culture for Aspergillus and/or a positive serum Aspergillus IgG or antigen. Radiological features on CT thorax may include consolidation cavitation, and fibrosis. Treatment is with antifungal therapy.
People with a mobile fungal mass occupying a previously formed pulmonary cavity. Aspergillomas are usually associated with high levels of serum Aspergillus IgG. Best outcomes are from surgical resection.
Nodule, or nodules with or without cavitation, often with necrosis caused by Aspergillus which can only be diagnosed histologically. May mimic tumours and other fungal infections.
The following investigations should be ordered in cases of symptomatic asthma or chronic lung disease where the cause of symptoms is not known, antibiotic therapy is typically partially or totally ineffective and where some form of aspergillosis is suspected clinically.
Antifungal susceptibility testing
Antifungal susceptibility testing of Aspergillus isolates should be performed in patients on antifungal therapy, with invasive disease (whether or not on antifungal therapy), or in patients who are clinically suspected of having an azole resistant pathogen (AIII).
|Empirical Antimicrobial Treatment|
|In general, antifungal treatment based on clinical suspicion of aspergillosis without any positive laboratory investigation results (see above) is not advised.|
|Directed Antimicrobial Treatment (when microbiology results are known)|
✛Important note: There are significant interactions between Itraconazole and a large number of other drugs particularly inhaled corticosteroids. Patients on inhaled corticosteroids and Itraconazole electronic Medicines Compendium information on Itraconazole should have their corticosteroid doses reduced to 25% of initial dose as Itraconazole electronic Medicines Compendium information on Itraconazole inhibits the CYP3A4 enzyme that metabolises inhaled steroids and high corticosteroid levels may lead to Cushing syndrome.14 Consider referring patients to a pharmacist for a medication review.
In patients whose clinical features don’t fit into these categories treatment should be agreed after discussion with a Microbiologist/mycologist.
* Voriconazole is known to be associated with a risk of liver toxicity, phototoxicity, and squamous cell carcinoma of the skin. Before commencing treatment with voriconazle, the following actions must be completed:
†NB: Posaconazole use is a protected antimicrobial with full restrictions and always requires a code from Microbiology. Voriconazole , Ambisome and Caspofungin are protected antimicrobials with partial restrictions, if used outside of LTHT guidelines it may only be prescribed after obtaining a code from Microbiology.
Long term therapy
It is increasingly realised that for many patients who tolerate and show response to azole therapy, long term treatment, possibly even lifelong treatment is likely to lead to the best outcomes. However, there is evidence that up to 10% of patients may suffer from peripheral neuropathy as a consequence of at least 4 months of triazole therapy. In most cases this is reversible on cessation of therapy 15. Long term therapy also clearly has economic implications.
|Switch to oral agent(s)|
|Recommendation: Patients on intravenous antifungal therapy should be switched to an oral azole after two weeks of therapy assuming good clinical progress17. [Evidence level C]|
Table 3: Antifungal regimens in intrinsic resistance
Abbreviations for Table 3 and 4:
Table 4: Optimal therapy in documented azole-resistance
Abbreviations for Table 3 and 4:
|All patients in which a diagnosis of pulmonary aspergillosis is considered should be referred to respiratory medicine.|
|Clinical condition:||Fungal infections in the immunocompetent respiratory medicine patient|
|Target patient group:||Adults|
|Target professional group(s):||Secondary Care Doctors
- Stevens Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P, Judson MA, Denning DW, Crameri R, Brody AS, Light M, Skov M, Maish W, Mastella G; Participants in the Cystic Fibrosis Foundation Consensus Conference. (2003) Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis 37 Suppl 3:S225-64.
- Guinea J, Torres-Narbona M, Gijon P, Munoz P, Pozo F, Pelaez T, de Miguel J, Bouza E 2010 Pulmonary Aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors and outcome. Clin Microbiol Infect 16:870-877
- Denning DW, Cadranel J, Beigelman-Aubrey C, Ader F, Chakrabarti A, Blot S, Ullman AJ, Dimopoulos G, Lange C on behalf of the European Society for Clinical Microbiologyt and Infectious Diseases and European Respiratory Society. 2016 Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Resp J 47: 45-68
- Prys Picard and Niven 2010 Severe asthma with fungal sensitization. In Aspergillosis from diagnosis to prevention. Ed Pasqualatto AC Springer, London
- Denning DW, O’Driscoll BR, Powell G, Chew F, Atherton GT, Vyas A, Miles, J, Morris J, Niven RM 2009 Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization. Am J Resp Crit Care Med 179:11-18
- Pasqualatto AC, Powell G, Niven R, Denning DW 2009 The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis Respirology 14:1121-27.
- Greenberger J 2002 Allergic Bronchopulmonary Aspergillosis J Allergy clin Immunol. 110:685-92.
- Bulpa P, Dive A, Sibille Y (2007)Invasive aspergillosis in patiens with chronic obstructive pulmonary disease Eur Resp J 30:782-800
- Stevens DA, Schwartz HJ, Lee JY, Moskovitz BL, Jerome DC, Catanzaro A, Bamberger DM, Weinmann AJ, Tuazon TU, Judson MA, Platts-Mills TAE, DeGraff AC A randomized trial of Itraconazole electronic Medicines Compendium information on Itraconazolein allergic bronchopulomary aspsergillosis New England J Med 342: 756-762.
- Wark PAB, Hensley MJ, Saltos N, Boyle MJ, Toneguzzi R, Simpson JL, McElduff P, Gibson PG Anti-inflammatory effect of Itraconazole electronic Medicines Compendium information on Itraconazolein stable allergic bronchopulmonary aspergillosis: A randomized controlled trial. 2003 J Allerg. Clin Immunol 111:952-7.
- Global Initiative for Chronic Obstructive Lung Disease 2009 Global Strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. http://www.goldcopd.org/Guidelineitem.asp?l1=2&l2=1&intId=2003
- De Pauw B, et al. 2008 Revised definitions of invasive fungal disease from the European organization for Research and treatment of Cancer /Invasive fungal infections cooperative group and the National Institute of Allergy and Infectious Diseases Mycoses study group (EORTC/MSG) Consensus group. Clin Infect. Dis 46:1813-21.
- Walsh T. et al. 2008 Treatment of Aspergillosis: Clinical Practice guidelines of the Infectious Diseases Society of America Clin. Infect Dis. 46:327-60.
- Naef R, Schmid C, Hofer M, Minder S, Speich R, Boehler A 2007. Itraconazole electronic Medicines Compendium information on Itraconazolecomedication increases systemic levels of fluticasone in Lung transplant recipients. Respiration 74:418-22
- Baxter CG, Marshall A, Roberts M, Felton TW, Denning DW 2011 Peripheral neuropathy in patients on long term triazole antifungal therapy. J. Antimicrobial therapy Jun 17 Epub
- Felton TW, Baxter C, Moore CB, Roberts SA, Hope WW, Denning DW 2010 Efficacy and safety of posaconazole for chronic pulmonary aspergillosis. Clin Infect Dis. 2010 51:1383-91.
- Denning DW, Riniotis K, Dobrashian R, Sambatakou H (2003) Chronic Cavitary and Fibrosing Pulmonary. and Pleural Aspergillosis: Case Series, Proposed Nomenclature Change, and Review Clin Infect Dis; 37(Suppl 3):S265–80
- De Beule K, De Doncker P, Cauwenbergh G, et al. The treatment of aspergillosis and aspergilloma with Itraconazole electronic Medicines Compendium information on Itraconazole, clinical results of an open international study (1982–1987). Mycoses 1988; 31:476–485.
- Jain LR, Denning DW. The efficacy and tolerability of voriconazole in the treatment of chronic cavitary pulmonary aspergillosis. J Infect 2006; 52:e133–e137.
- Maertens JA, Raad II, Marr KA, Patterson TF, Kontoyiannis DP, Cornely OA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (secure): a phase 3, randomised-controlled, non-inferiority trial. Lancet 2016;387:
- Guinea J, Torres-Narbona M, Gijon P, Munoz P, Pozo F, Pelaez T, et al. Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin Microbiol Infect 2010;16:870e7.
- He H, Ding L, Li F, Zhan Q. Clinical features of invasive bronchial-pulmonary aspergillosis in critically ill patients with chronic obstructive respiratory diseases: a prospective study. Crit Care 2011;15:R5.
- Bulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Respir J 2007;30:782e800.
- Pegorie M, et al., Estimating the burden of invasive and serious fungal disease in the United Kingdom, J Infect (2016), http://dx.doi.org/10.1016/j.jinf.2016.10.005
- Ullman AJ et al 2018 Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Micro Infect 24:e1-e38.
A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.
D. Leeds consensus. (where no national guidance exists or there is wide disagreement with a level C recommendation or where national guidance documents contradict each other)
Improving Antimicrobial Prescribing Group
LHP version 2.0
IgG (non-allergic) response to Aspergillus also often called ImmunoCAP, equates to precipitin test
IgE (allergic response) to Aspergillus formerly called RAST
General marker of allergy/atopy
Direct detection of antigen in invasive disease also called galactomannan
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