Detection of Azole Resistance Inducing Mutations on DNA Extracted Directly From Serum or Plasma of Immunocompromised Patients With an Invasive Aspergillus Infection Azole Resistance PCR Optimalization-study

Study Overview
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Brief Summary
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Invasive aspergillosis (IA) is the most common mould infection in immunocompromised patients with haematological disease. Voriconazole, a triazole, improves overall survival of patients with an IA and is the mainstay of therapy. Resistance of A. Fumigatus emerged as an important clinical problem and infections with azole resistant Aspergillus have a high mortality. Nowhere in the world, azole resistance is more prevalent than in the Netherlands. Rapid detection of resistance is key to improve the patient's outcome but fungal cultures take time and are often negative. The investigators aim to detect azole resistance associated mutations in fungal DNA extracted directly from serum or plasma to accelerate diagnosis and improve outcome of patients infected with azole resistant A. fumigatus.

Official Title
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Detection of Azole Resistance Inducing Mutations on DNA Extracted Directly From Serum or Plasma of Immunocompromised Patients With an Invasive Aspergillus Infection Azole Resistance PCR Optimalization-study

Conditions
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Invasive Aspergillosis

Intervention / Treatment
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* Diagnostic Test: Aspergillus PCR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older. Lung CT shows lesions that fulfil the EORTC/MSG radiological criteria of possible invasive fungal infection. A bronchoalveolar lavage is planned or has been performed <48hrs earlier Exclusion Criteria: - Patients unable or unwilling to provide consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Aspergillus PCR|Aspergillus PCR will be performed on different volumes of serum and plasma of patients with hematological malignancies with suspicion for invasive fungal infection.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance of two different PCR test | The sensitivity and specificity will be determined of the different PCR's tested including the commercially available AsperGenius (Pathonostics, Maastricht) and the in-house PCR. For this purpose a patients diagnosed with proven or probable IPA according to the EORTC/MSG definition will be used as the gold standard. | 1 week | 
| Performance of two different media for the PCR test | Extraction medium (serum versus plasma) and extraction volume (1, 3 or 10 ml) that results in best sensitivity and specificity will be determined | 1 week | 
| Determination of best PCR cycle threshold | Extraction medium (serum versus plasma) and extraction volume (1, 3 or 10 ml) that results in best sensitivity and specificity will be determined | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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invasive aspergillosis, PCR