title: Therapy with antifungals decreases the diagnostic performance of PCR for diagnosing invasive aspergillosis in bronchoalveolar lavage samples of patients with haematological malignancies.
abstract: OBJECTIVE
  Invasive aspergillosis (IA) is a life-threatening infection in severely immunocompromised patients, especially those receiving intensive chemotherapy or undergoing haematopoietic stem cell transplantation. As the clinical diagnosis of IA is mostly based on biomarkers (galactomannan, β-d-glucan, PCR assays) indicating Aspergillus as the underlying pathogen, the effect of antifungal treatment on the performance of these parameters is still controversial. We evaluated the effect of antifungal treatment on the performance of an Aspergillus-specific PCR assay in bronchoalveolar lavage (BAL) samples.
  
  
  METHODS
  Two-hundred-and-twenty-six BAL samples from 226 patients with haematological malignancies at high risk for IA classified according to the 2008 European Organization for the Research and Treatment of Cancer criteria were analysed retrospectively for the diagnostic performance of a nested Aspergillus PCR assay in relation to the number and type of mould-active antifungals received prior to BAL sampling.
  
  
  RESULTS
  Sensitivity of BAL PCR for patients without antifungal treatment prior to BAL sampling was 0.69, whereas specificity was 0.87. While no significant change in diagnostic performance by the addition of one antifungal was observed, receiving two or more antifungals prior to BAL sampling led to a significant decrease in the diagnostic performance of BAL PCR testing (P < 0.009).
  
  
  CONCLUSIONS
  Treatment with mould-active antifungals prior to BAL sampling significantly decreases the performance of the Aspergillus PCR assay in haematological patients if BAL was performed after administration of more than one antifungal agent. Performing BAL sampling for Aspergillus PCR diagnostic despite pre-treatment with one antifungal or while on prophylaxis is feasible.
authors: Mannheim University Hospital, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim, Germany. mark.reinwald@medma.uni-heidelberg.de
authors: Mark
authors: M
authors: Reinwald
authors: Margit
authors: M
authors: Hummel
authors: Elena
authors: E
authors: Kovalevskaya
authors: Birgit
authors: B
authors: Spiess
authors: Werner J
authors: WJ
authors: Heinz
authors: Jörg Janne
authors: JJ
authors: Vehreschild
authors: Beate
authors: B
authors: Schultheis
authors: Stefan W
authors: SW
authors: Krause
authors: Bernd
authors: B
authors: Claus
authors: Thomas
authors: T
authors: Suedhoff
authors: Rainer
authors: R
authors: Schwerdtfeger
authors: Stefan
authors: S
authors: Reuter
authors: Michael G
authors: MG
authors: Kiehl
authors: Wolf-Karsten
authors: WK
authors: Hofmann
authors: Dieter
authors: D
authors: Buchheidt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage*; D001228:Aspergillosis / Q000175:diagnosis / Q000382:microbiology*; D001230:Aspergillus / Q000302:isolation & purification*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology*; D018890:Chemoprevention / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications*; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D009172:Mycology / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D000935:Antifungal Agents