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European societies issue aspergillosis guidelines.

FROM JOURNAL OF DRUGS IN DERMATOLOGY

European respiratory disease and infectious disease specialists have banded together to issue new clinical guidelines on the diagnosis and management of an uncommon but serious problem: chronic pulmonary aspergillosis (CPA).

Pulmonary infections with Aspergillus species, although uncommon, are a complicating factor in several lung diseases, especially tuberculosis, and aspergillosis is a serious, often fatal opportunistic infection in transplant recipients who are on chronic immunosuppression or patients who are immunocompromised from disease or cytotoxic chemotherapy.

Approximately 240,000 people in Europe and 3 million people worldwide have chronic pulmonary aspergillosis (CPA). The Centers for Disease Control and Prevention notes that because aspergillosis is not classified as a reportable disease, data on the actual incidence of infections in the United States are hard to come by.

The guidelines, issued by the European Society for Clinical Microbiology and Infectious Diseases in cooperation with the European Confederation of Medical Mycology and the European Respiratory Society, are an attempt to provide clinicians with the best possible evidence-based guidance on managing patients with aspergillosis, primarily those with CPA (Eur Respir J. 2015. doi: 10.1183/13993003.00583-2015).

Dr. Norman Edelman, a pulmonologist and senior consultant for scientific affairs for the American Lung Association, noted that the most frequent presentation he sees--and that very infrequently--is allergic bronchopulmonary aspergillosis in patients with asthma.

The most recent U.S. guidelines, issued under the aegis of the Infectious Diseases Society of America (IDSA) in 2000 and revised in 2008 (CID 2008;46:327-360), offer less detail than the European recommendations, explained Prof. David W. Denning, professor of infectious diseases in global health at the University of Manchester (England) and the European guidelines' lead author.

"The European ones go into in great detail--the diagnosis, the radiology, whether this test is better than that test, how they all add up, and all that sort of stuff," he said in an interview.

The European guidelines also make recommendations for duration of therapy and comment on the use of steroids and immunotherapy with interferon-gamma, Dr. Denning noted.

Diagnostic criteria

The European guidelines categorize Aspergillus infections according to differences in clinical management:

* Simple aspergilloma. A single pulmonary cavity containing a fungal ball, supported by serologic or microbiologic evidence of infection with Aspergillus species in patients who are not immunocompromised and are asymptomatic or have only minor symptoms and no radiographic evidence of progression for at least 3 months.

* Chronic cavitary pulmonary aspergillosis (CCPA). The presence of one or more pulmonary cavities that may contain one or more aspergillomas or irregular intraluminal material, evidence of Aspergillus species, significant pulmonary/systemic symptoms, and overt progression on radiography over 3 or more months of observations.

* Chronic fibrosing pulmonary aspergillosis (CFPA). Severe, fibrotic destruction of at least two lung lobes as a complication of CCPA, causing a major loss of lung function. The guidelines note that destruction of a single lobe is designated as CCPA of that lobe.

* Aspergillus nodules. This unusual presentation is marked by the presence of one or more nodules that may or may not cavitate. The nodules may resemble tuberculoma, carcinoma of the lung, or coccidioidomycosis; histology is required to make an accurate diagnosis.

* Subacute invasive aspergillosis (SAIA). This can occur over the course of 1-3 months in patients who are mildly immunocompromised. Radiologic features can vary, and may include cavitation, the presence of nodules, and progressive consolidation with the appearance of abscess formation. Fungal hyphae (filaments) can be seen in biopsied lung tissues, and there may be evidence of Aspergillus galactomannan antigen in respiratory fluids or blood.

Treatment

The guidelines note that most of the evidence for managing CPA are based on cohort studies and case reports rather than randomized clinical trials, and that there have been no head-to-head trials comparing oral triazole agents.

For treatment of CPA, the European guidelines recommend:

* Itraconazole 200 mg twice daily, with therapeutic drug monitoring and dose adjustment as necessary (Grade A [strong] recommendation).

* Voriconazole 150-200 mg twice daily, with monitoring and dose adjustment. The guidelines recommend lower doses for patients older than 70 years, those with low body weight, significant liver disease, and/or those of Northeast Asian descent, who may be genetically inclined to slow drug metabolism (Grade A).

* Posaconazole liquid 400 mg twice daily, or tablets 300 mg once daily (Grade B [moderate] recommendation]. In general, the recommended duration of therapy for control of infection in patients with CPA or curative intent for patients with SAIA or chronic necrotizing pulmonary aspergillosis is 6 months or more, depending on patient status and drug tolerance. For patients with CPA with progressive disease, those whom therapy has failed, or those who are intolerant of or have disease resistant to triazoles, intravenous therapy with micafungin, 150 mg day (Grade B); amphotericin B deoxycholate, 0.7-1.0 mg/kg per day (Grade C [marginal] recommendation); liposomal amphotericin B, 3 mg/kg per day (Grade B); or caspofungin, 50-70 mg/day (Grade C) are recommended.

The guidelines were funded primarily by grants from ESCMID and ERS with additional support from ECMM. Authors' travel expenses were funded jointly by ESCMID and ERS. Dr. Denning has received financial support from numerous drug companies and government bodies. Dr. Edelman reported no relevant disclosures.

BY NEIL OSTERWEIL

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Title Annotation:INFECTIOUS DISEASES
Author:Osterweil, Neil
Publication:Family Practice News
Date:Jan 1, 2016
Words:871
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