Aspergillus specific nested PCR from the site of infection is superior to testing concurrent blood samples in immunocompromised patients with suspected invasive aspergillosis.

Tobias Boch,Michael Kiehl,Oliver A Cornely,Matthias Duerken,Peter Markus Deckert,Wolf‐Karsten Hofmann,Hartmut Bertz,Bernd Claus,Mark Reinwald,Werner Heinz,Dieter Buchheidt,Stefan Reuter,Rainer Schwerdtfeger,Birgit Spiess,Stefan W Krause,Joachim Hahn

doi:10.1111/myc.12983

Abstract

Invasive aspergillosis (IA) is a severe complication in immunocompromised patients. Early diagnosis is crucial to decrease its high mortality, yet the diagnostic gold standard (histopathology and culture) is time-consuming and cannot offer early confirmation of IA. Detection of IA by polymerase chain reaction (PCR) shows promising potential. Various studies have analysed its diagnostic performance in different clinical settings, especially addressing optimal specimen selection. However, direct comparison of different types of specimens in individual patients though essential, is rarely reported. We systematically assessed the diagnostic performance of an Aspergillus-specific nested PCR by investigating specimens from the site of infection and comparing it with concurrent blood samples in individual patients (pts) with IA. In a retrospective multicenter analysis PCR was performed on clinical specimens (n=138) of immunocompromised high-risk pts (n=133) from the site of infection together with concurrent blood samples. 38 pts were classified as proven/probable, 67 as possible and 28 as no IA according to 2008 European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions. A considerably superior performance of PCR from the site of infection was observed particularly in pts during antifungal prophylaxis (AFP)/antifungal therapy (AFT). Besides a specificity of 85%, sensitivity varied markedly in BAL (64%), CSF (100%), tissue samples (67%) as opposed to concurrent blood samples (8%). Our results further emphasise the need for investigating clinical samples from the site of infection in case of suspected IA to further establish or rule out the diagnosis.

Highlights

Invasive aspergillosis (IA) is a severe, life‐threatening complication in immunocompromised patients, contributing significantly to morbidity and mortality.[1]
IA is underdiagnosed and, in most cases, antifungal therapeutic efforts are initiated empirically merely based on clinical criteria, e.g. suspicious lung infiltrates on chest computed tomography (CT) scans
The significance of polymerase chain reaction (PCR) assays for detection of fungal pathogens is rising and it will supposedly find its way into the upcoming new EORTC/MSG criteria and is already included in the recent ECCMID Guidelines.[22]. In this context we further investigated the diagnostic potential of an established Aspergillus PCR assay for diagnosis of IA with special regard to optimal type of specimen and prior antifungal treatment

Summary

Introduction

Invasive aspergillosis (IA) is a severe, life‐threatening complication in immunocompromised patients (pts), contributing significantly to morbidity and mortality.[1]. IA is underdiagnosed and, in most cases, antifungal therapeutic efforts are initiated empirically merely based on clinical criteria, e.g. suspicious lung infiltrates on chest computed tomography (CT) scans. The limitations of this approach have been depicted in a study that found only around 50% of pts with CT based IA diagnosis to truly harbour IA after surgical removal of suspected tissue.[8]

Results

Discussion

Conclusion