From Antimicrobial Activity to Topical Translation: An Integrated Framework for Testing, Cytotoxicity Assessment and Formulation of Plant Extracts, Essential Oils and Honey.

Background/Objectives: Antimicrobial resistance has renewed interest in plant extracts, essential oils and honey as topical adjuvants, yet antimicrobial potency, host-tissue safety and formulation performance are usually reported in separate bodies of literature, and the material tested is often characterized only superficially. This structured narrative review aimed to integrate these dimensions into a single decision-oriented pathway. Methods: The Web of Science Core Collection was searched using seventeen predefined strings across fourteen thematic domains, restricted to English-language articles and reviews from 2021 to 2026, with supplementary PubMed/MEDLINE searches, hand-searching, and normative documents from the issuing organizations. Results: The framework comprises seven decision domains: pre-analytical standardization of each matrix class; antibacterial and antifungal testing with matrix-specific controls; biofilm endpoints named according to what they measure; strain selection tiered from reference to clinical and resistant isolates; host safety from monolayer cytotoxicity to reconstructed human epidermis; selectivity, expressed per microorganism and extended to the resident cutaneous microbiota; and formulation performance, with permeation interpreted against a retention rather than a maximization target. Resistance under sub-inhibitory exposure forms an advanced stage. Conclusions: Progression is governed by proposed Go, Conditional Go and No-Go criteria, supported by a matrix-specific control table and a minimum reporting checklist. The framework has not been prospectively validated, and no universal selectivity threshold is proposed.