More Detection, Better Decisions? Rethinking Pathogen-Driven Therapy in Diabetic Foot Infections

Pathogen-driven therapy is central to the management of diabetic foot infections (DFIs), where antimicrobial selection relies on microbiological identification. Over the past decade, diagnostic capabilities have expanded from conventional cultures to high-resolution molecular sequencing, substantially increasing pathogen detection. Whether this expansion translates into better therapeutic decisions, however, remains uncertain. This narrative review examines the roles and limitations of culture-based methods, antimicrobial susceptibility testing, targeted polymerase chain reaction panels, 16S rRNA gene sequencing, and shotgun metagenomics in DFIs. Culture remains the cornerstone of pathogen-directed therapy because it identifies viable organisms and provides phenotypic susceptibility data that inform antibiotic selection and de-escalation. Molecular techniques broaden detection and reveal polymicrobial complexity and resistance genes, yet increased analytical sensitivity does not consistently clarify pathogen prioritization, distinguish colonization from infection, or improve patient-centered outcomes. Intensified diagnostic strategies often lead to antimicrobial modification without clear gains in healing or cost-effectiveness. These findings underscore a persistent interpretative gap: detection capacity has advanced more rapidly than frameworks linking microbiological data to meaningful therapeutic action. Microbiology is indispensable but insufficient in isolation. Improved outcomes will depend less on detecting additional organisms and more on integrating microbiological findings with surgical management, vascular status, and multidisciplinary care.