SIOOT oxygen-ozone therapy against multidrug resistant bacteria. Perspectives and future remarks

Introduction

Antibiotic resistance is one of the most pressing global health threats, diminishing the effectiveness of standard antimicrobial therapies and contributing to increased morbidity, mortality, and healthcare costs. In response to this challenge, ozone therapy has emerged as a potential adjunctive treatment against multidrug-resistant (MDR) bacterial infections. Notably, protocols endorsed by the Italian Scientific Society of Oxygen-Ozone Therapy (SIOOT) and clinical insights from Prof. Marianno Franzini, have advanced understanding of ozone dual mechanisms of action in infection control.

Methods

This review synthesizes data from experimental studies, modelling analyses, and clinical reports on the use of medical ozone in MDR infections. Mechanistic insights focus on two principal modes: (1) direct bactericidal activity of ozone and its reactive species through oxidative damage to microbial membranes and thiol groups, and (2) systemic immunomodulation via low-dose ozone exposure. The latter is mediated by secondary messengers such as 4-hydroxynonenal, which activate Nrf2 signaling, regulate inflammasomes, promote macrophage activity, and enhance mitochondrial function.

Results

Evidence indicates that ozone exerts rapid, broad-spectrum bactericidal effects largely independent of classical resistance mechanisms. When administered systemically within a hormetic dose range, ozone enhances host innate immunity through redox-sensitive signaling pathways and promotes tissue-level resilience. Modelling studies suggest synergistic effects when ozone is combined with antibiotics, accelerating pathogen clearance compared to antibiotic monotherapy. Clinically, ozone has demonstrated efficacy as an adjunct in treating chronic wounds and necrotizing infections caused by MDR pathogens.

Conclusions

Ozone therapy, when precisely dosed and integrated into standardized medical protocols, offers a compelling adjunctive approach in the management of antibiotic-resistant infections. Rather than replacing antibiotics, ozone augments their effectiveness and may reduce the selective pressure driving resistance. Future integration of ozone into antimicrobial stewardship programs could support more sustainable, system-based infection control strategies aligned with global health imperatives.