Next Steps: Studying Diabetic Foot Infections with Next-Generation Molecular Assays

Abstract Purpose of Review In 2019, the International Working Group on the Diabetic Foot voiced six concerns regarding the use of molecular microbiology techniques for routine diagnosis of infection complicating diabetic foot ulcers. The purpose of this review is to evaluate contemporary evidence addressing each of these concerns and describe promising avenues for continued development of molecular microbiology assays. Recent Findings Since 2019, the feasibility of conducting metagenomic and metatranscriptomic studies on diabetic foot ulcer samples has been shown. However, these preliminary studies used small samples with concerns for selection bias. We await larger-scale, longitudinal studies, potentially using the recently formed Diabetic Foot Consortium, to identify microbiome profiles associated with infection and patient outcomes. How these results would translate into a clinical diagnostic requires further clarification. Summary High-throughput molecular microbiology techniques are not yet ready for clinical adoption as first-line diagnostics. However, moving from amplicon sequencing to metagenomic and metatranscriptomic studies has the potential to significantly accelerate development of assays that might meaningfully impact patient care.