Beyond susceptibility testing: traditional Chinese medicine-associated compounds as candidate antibiotic adjuncts in chronic-wound biofilms.

Chronic-wound infections may respond poorly even when routine testing shows that the infecting organism remains susceptible. In tissue, bacteria occupy aggregates shaped by oxygen and nutrient gradients, host material, diabetes-associated chemistry and uneven antibiotic exposure. These conditions can slow killing and favour small-colony variants or intracellular survival, particularly in Staphylococcus aureus. Human evidence for these phenotypes is strongest in diabetes-related foot infection and associated bone, whereas evidence for intracellular Pseudomonas aeruginosa in wounds remains largely experimental. We examined whether chemically defined compounds associated with traditional Chinese medicine (TCM) might improve antibiotic performance in this setting. The most persuasive preclinical studies connect a compound to antibiotic entry, target regulation or viable killing. Weaker reports rely on early-biofilm biomass, checkerboard interaction or formulation effects that cannot be assigned to the phytochemical itself. Cinnamaldehyde, chenodeoxycholic acid, sodium houttuyfonate and 5, 8-dihydroxy-1, 4-naphthoquinone provide useful mechanistic or infected-wound leads, but the evidence remains fragmented across organisms and models. As of 12 August 2026, we found no controlled human study showing that a chemically defined TCM-associated compound used as an antibiotic adjunct clears mature chronic-wound biofilm, prevents infectious relapse or safely reduces antibiotic exposure. Progress now depends on testing fewer, well-defined combinations in mature polymicrobial systems. Such studies should measure post-treatment regrowth, infection-site exposure and tissue compatibility alongside bacterial killing.