Determinants of Microbial Resistance to Far-UVC 222 nm in Healthcare Pathogens: A Narrative Review

Far-UVC 222 nm is a promising adjunctive disinfection technology for occupied healthcare environments, though antimicrobial efficacy varies significantly across pathogen types due to fundamental differences in microbial biology. This review synthesizes evidence on microbiological determinants of far-UVC resistance, examining cell envelope structure, biofilm formation, DNA repair capacity, and antioxidant defenses. A clear resistance hierarchy emerges. Enveloped viruses lacking enzymatic repair systems are highly vulnerable, requiring fluences below 3 mJ/cm2. Gram-negative bacteria are readily inactivated through membrane disruption and reactive oxygen species accumulation. Gram-positive bacteria demonstrate higher resistance via thick peptidoglycan barriers, DNA repair mechanisms, and redundant antioxidant systems. Biofilm-embedded cells show 10–1000-fold increased tolerance due to protective extracellular matrices, stress-response gene upregulation, and microenvironmental heterogeneity. Clostridioides difficile spores exhibit extreme resistance through multilaminar protective coats and metabolic dormancy, requiring impractical doses exceeding 1000 mJ/cm2. Field studies in real-world polymicrobial biofilm communities demonstrate substantially lower efficacy than laboratory predictions, typically achieving only 55–81% bioburden reductions. Understanding these pathogen-specific resistance mechanisms is essential for the rational deployment of far-UVC as an adjunctive infection prevention intervention in healthcare settings.