Surveillance of Azole Resistance in Aspergillus Isolates in Taiwan

Study Overview
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Brief Summary
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Primary objectives: To investigate the prevalence of azole resistance in Aspergillus clinical isolates collected in participating hospitals in Taiwan To investigate the prevalence of azole resistance in Aspergillus environmental isolates in Taiwan To characterize the molecular mechanisms of azole resistance in Aspergillus isolates in Taiwan To investigate the clonality of Aspergillus clinical and environmental isolates in Taiwan To describe the genetic relationships between local resistant strains with global strains Secondary objective: To describe the clinical characteristics and treatment outcome of patients with proven or probable invasive aspergillosis To evaluate the clinical impact of azole resistance in patients with proven or probable invasive aspergillosis in a case-control study

Detailed Description
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Cumulative evidence described the emergence and geographical expansion of azole-resistant Aspergillus fumigatus associated with azole treatment failure. Multiple amino acid substitutions in the cyp51A gene have been described to be associated with azole resistance that emerges during azole treatment, while a resistance mechanism, TR34/L98H mutation in cyp51A, has been linked to the agricultural use of azole fungicides in Europe, which have also been widely used in Taiwan for years. The current prevalence of azole-resistant Aspergillus isolates and mechanisms of azole resistance in Taiwan is not clear. Considering the potential of geographic migration of resistant isolates from neighboring countries and the possibility of emergence of locally revolved resistant strains, this 2-year multi-center project aims to investigate the prevalence rate of azole resistance in Aspergillus clinical and environmental isolates, to determine the molecular mechanisms of azole resistance, and to describe the clinical characteristics and treatment outcome of Aspergillus diseases in Taiwan. Clinical and environmental Aspergillus isolates will be collected and examined, and clinical data from patients with Aspergillus diseases or colonization will be retrieved and analyzed. Through this study the investigators anticipate increase in awareness of prevalence and impact of azole resistance in patient safety in participating hospitals. In addition, the investigators may update Taiwan treatment guideline for aspergillosis on the basis of these evidence and knowledge.

Official Title
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Surveillance of Azole Resistance in Aspergillus

Conditions
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Infection; Aspergillus

Participation Criteria
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Eligibility Criteria
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For primary objectives Inclusion Criteria: Patients with one or more clinical specimens culture positive of Aspergillus Exclusion Criteria: Is not a human pathogen of Aspergillus no clinical data available For secondary objectives (a case-control study in a 1:4 ratio) Inclusion Criteria: patients with proven or probable invasive aspergillosis Case patients: patients infected by azole-resistant isolates Control patients: patients infected by azole-susceptible isolates
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment success | The proportion of patients with complete response or partial response according to the definition described in Segal BH, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, Sobel J, Viscoli C, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis. Sep 1 2008;47(5):674-683. | 6 weeks after diagnosis of proven or probable invasive aspergillosis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | The proportion of non-survivors. Discharge against medical advice and in critical condition and lost to follow up will categorized as mortality. | 6 weeks after diagnosis of proven or probable invasive aspergillosis | 
| All-cause mortality | The proportion of non-survivors. Discharge against medical advice and in critical condition and lost to follow up will categorized as mortality. | 12 weeks after diagnosis of proven or probable invasive aspergillosis | 
| Breakthrough mold infections | The proportion of patients with breakthrough mold infections | 6 weeks after diagnosis of proven or probable invasive aspergillosis | 
| Breakthrough invasive fungal diseases | The proportion of patients with breakthrough invasive fungal diseases defined as occurrence of a proven or probable invasive fungal diseases according to EORTC/MSG revised definitions while on systemic antifungal therapy or within 15 days of discontinuation of antifungal use | 12 weeks after diagnosis of proven or probable invasive aspergillosis | 
| Treatment success | The proportion of patients with complete response or partial response. | 12 weeks after diagnosis of proven or probable invasive aspergillosis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aspergillus, Antifungal susceptibility, Azole resistance