Evaluating emerging molecular diagnostics for severe infections in neutropenic patients with hematological malignancies

INTRODUCTION: Neutropenia significantly increases infection risk in hematologic malignancies patients, when clinical signs are often subtle and fever may be the only indicator. Molecular diagnostic methods promise faster, more sensitive pathogen detection compared to conventional methods, aiming to improve timely and appropriate therapy. AREAS COVERED: This review summarizes emerging molecular diagnostics for severe infections in neutropenic hematological malignancies patients, focusing on microbiological performance and, where available, clinical impact. We conducted a search in PubMed and Embase using subject headings: 'molecular diagnosis,' 'neutropenic,' 'infections,' 'hematological malignancies,' supplemented by information from manufacturers of commercial assays. The technologies reviewed include multiplex polymerase chain reaction, microarray-based assays, metagenomic and targeted next-generation sequencing, host transcriptomics, and methods for diagnosing invasive fungal infections. For each, we describe key characteristics, diagnostic performance, and clinical utility when reported. EXPERT OPINION: Emerging molecular diagnostics shorten time to pathogen and resistance identification and broaden detection of organisms in febrile neutropenic patients with hematological malignancies. These methods are best integrated as complements to culture-based methods within centers with antimicrobial stewardship programs, where they inform earlier targeted therapy and rational de-escalation of antimicrobials. Priority actions include prospective trials powered for measuring clinical outcomes and economic endpoints, with standardized workflows, reporting, and quality assurance to enable clinical implementation.