Background: Invasive mould infections (IMI) carry high morbidity and mortality. Conventional diagnostics-histopathology, culture and microscopy-rely on invasive sampling and lack sensitivity, particularly during early phases of infection. Rare and mixed mould infections are frequently diagnosed too late or missed.
Objectives: To provide a narrative review of recent innovations in diagnosing IMIs, highlighting advances, identifying areas where progress remains limited, and assessing gaps in current diagnostic algorithms to guide future directions.
Sources: We performed a literature search regarding diagnostic methods for IMIs without date restrictions, including experimental and clinical studies, systematic reviews and meta-analyses.
Content: Rapid lateral flow assays and single-sample chemiluminescent immunoassays for detecting Aspergillus antigens in blood and bronchoalveolar lavage fluid now complement enzyme immunoassays. Novel targets, such as urinary glycans and siderophores in various biological matrices, show potential to diagnose IMI. Targeted PCRs for Aspergillus and Mucorales enable earlier detection than conventional methods and rapid detection of resistance in case of A. fumigatus, although isolated Aspergillus PCR positivity is challenging to interpret. Metagenomic next-generation sequencing expands pathogen detection but is limited by costs and technical and interpretative challenges. A shift towards assays based on the host immune response (functional immune assays and biochemical markers) shows promise but remains investigational.
Implications: Due to different commercially available test formats, Aspergillus antigen detection assays can now be implemented in many hospitals. Implementation of Mucorales PCR tests improves the diagnosis of mucormycosis also in the setting of coinfections. Multimodal pathogen-based strategies that integrate antigen assays, targeted PCRs, and, in select cases, metagenomic next-generation sequencing enable earlier, more accurate, and comprehensive diagnosis of IMIs, ultimately improving clinical outcomes; but the need for rapid, accurate, noninvasive diagnostic tests for IMIs remains. Host-response-based assays are not yet clinic-ready. Prospective multicentre studies are needed to standardize diagnostic thresholds, validate novel diagnostic markers and to evaluate impact on patient outcomes and cost-effectiveness.
Background: Hybrid effectiveness-implementation studies simultaneously assess clinical effectiveness and implementation, thereby accelerating the translation of research into healthcare practice. Such designs are relevant in infection prevention and control (IPC) and infectious diseases (ID), where research-informed interventions frequently face barriers to real-world adoption, implementation, and sustainment. Implementation science offers methods and frameworks to bridge this research-to-practice gap, but the application of hybrid studies remains limited in IPC/ID.
Objectives: This narrative review aims to give an overview and characterize the use of hybrid effectiveness-implementation studies in IPC and ID research by identifying hybrid studies and protocols, analysing IPC/ID interventions and implementation strategies employed, summarizing implementation and effectiveness outcomes reported, and identifying gaps and opportunities for advancing the field.
Sources: We systematically searched Medline, Embase, CINAHL, Cochrane, and Clinicaltrials.gov to identify study reports, study protocols, and trial registries published in English, addressing both implementation and clinical effectiveness of IPC/ID interventions in acute inpatient settings.
Content: Twenty-six hybrid effectiveness-implementation studies were included, predominantly from high-income countries. The studies commonly evaluated effectiveness outcomes such as patient safety, service efficiency, and patient mortality. Frequently reported implementation outcomes included intervention and implementation fidelity, acceptability, adoption and feasibility, and implementation determinants (barriers and facilitators). Diverse conceptual theories, models, and frameworks from implementation science were employed. We identified opportunities for improving hybrid study reporting, including inconsistent labelling of hybrid methods, conceptual overlap between effectiveness and implementation outcomes, particularly fidelity, and fragmented reporting practices separating clinical effectiveness and implementation results.
Implications: Improving and standardizing reporting of hybrid studies, and expanding hybrid studies to diverse geographical and resource settings could substantially enhance the impact of IPC/ID interventions. Clearer distinction and labelling of hybrid designs and increased methodological rigour would improve comparability across studies, facilitating broader learning and greater real-world applicability of IPC/ID research.

