Skin and soft tissue infections: swab or biopsy? A diagnostic dilemma

PURPOSE OF REVIEW: Skin and soft tissue infections (SSTIs) are frequent clinical conditions in which microbiological investigation is selectively indicated. When an etiological diagnosis is pursued, the optimal sampling method - superficial swab vs. deep tissue biopsy or aspirate - remains controversial. This review critically examines the diagnostic performance, clinical impact, and limitations of different sampling strategies in SSTIs. RECENT FINDINGS: Evidence consistently shows that deep tissue biopsy or aspirate provides a higher microbiological yield and better correlation with clinical infection than superficial swabs, particularly in chronic or complex SSTIs such as diabetic foot infections and pressure ulcers. Studies including the CODIFI and CODIFI2 trials demonstrate that tissue samples identify more clinically relevant pathogens and fewer contaminants. However, this improved microbiological accuracy does not necessarily translate into better clinical outcomes or faster healing. Swab cultures remain widely used due to their simplicity and low invasiveness, but are limited by contamination and poor representation of deep infection. Emerging molecular techniques applied to swabs, including rapid PCR and 16S/18S rRNA sequencing, show high sensitivity for selected pathogens and offer faster results, although interpretation is challenging in polymicrobial or colonized wounds. SUMMARY: Deep tissue sampling or aspirates remain the microbiological gold standard for complex SSTIs, while superficial swabs may be appropriate in selected, mild infections or when invasive procedures are not feasible. Future diagnostic strategies should integrate clinical assessment, optimized sampling techniques, and molecular diagnostics within a tiered, stewardship-oriented approach to improve accuracy while avoiding unnecessary invasiveness and antibiotic overuse.