Re: 'Diagnostic limitations and challenges in current clinical guidelines and potential application of metagenomic sequencing to manage pulmonary invasive fungal infections in patients with haematological malignancies' by Park et al.

Background Pulmonary invasive fungal infections (pIFI) disproportionately affect patients with haematological malignancies (HM). Establishing a rapid and accurate diagnosis of pIFI is challenging. Multiple guidelines recommend diagnostic testing of invasive fungal infections but lack consensus and may contribute to inconsistent diagnostic approaches. Objective To identify key diagnostic challenges and review metagenomic sequencing data. Sources PubMed, professional consortium, and scientific society websites search to identify relevant, published, evidence-based clinical guidelines within the past five years. PubMed search for papers describing clinically relevant novel diagnostic technologies. Content Current guidelines of patients with HM and suspected pIFI recommend chest CT imaging and specimen testing with microscopic examination (including calcofluor white stain, histopathology, cytopathology etc), Aspergillus galactomannan, beta-D-glucan, PCR, and culture, each with certain limitations. Emerging real-world data support the adjunctive use of metagenomic sequencing-based tests for the timely diagnosis of pIFI. Implications High quality evidence from robust clinical trials is needed to determine whether guidelines should be updated to include novel diagnostic technologies. Trials should ask whether the combination of powerful novel diagnostics such as pathogen-agnostic metagenomic sequencing technologies in conjunction with conventional testing can optimize the diagnostic yield for all potential pIFI pathogens that impact the health of patients with HM.