The therapeutic actions of gaseous ozone/oxygen mixtures applied to wounds have long been recognized. Only recently, however, have we seen major advances in the understanding of their biochemical and physiological mechanisms.

The wound healing properties of ozone/oxygen gas mixtures, although mainly attributed to their pan-antimicrobial profile, involve other, increasingly appreciated mechanisms: bacterial toxin neutralization, microbial biofilm destruction, increased local blood oxygen partial pressure, and vasodilatation of the microvascular network of wounds, leading to the enhanced delivery of immune factors and antibiotics, and to the speedier removal of wound metabolic waste products. In addition, there is documentation that exposing bacterial species to ozone makes them markedly more susceptible to the action of antibiotics.

In unison, the understanding of the physico-chemistry of therapeutic ozone/oxygen gas mixtures has advanced considerably. Mixtures of oxygen, ozone, and distilled water—as a calibrated humidity component—in a context of selected temperature gradients, yield variable proportions of transitional compounds that possess potent biological activity. These include, aside from ozone and oxygen, hydrogen peroxides, peroxone and dihydrogen trioxide, among others. All these products eventually break down to form water and oxygen.

Inactivation of Gram-positive and Gram-negative bacteria by these ozone-generated compounds occurs via their reaction with bacterial components, especially lipids, lipopolysaccharides and lipoproteins. External bacterial organs challenged by ozone include their cell envelopes—formed of lipid-rich cytoplasmic membranes—and their peptidoglycan layers. Internally, bacterial organelles such as ribosomes and plasmids are susceptible to ozone’s diffusion into bacterial cytoplasm. Bacterial families typically infecting wounds include E. coli, Streptococcus, Staphylococcus, Klebsiella, Proteus, Pseudomonas, Bacteroides, Legionella, Yersinia and Mycobacteria, among others. Also ozone-sensitive, and implicated in gangrene, are anaerobic bacteria, such as Clostridium.

Fungi, ubiquitous tenants of wounds, are systematically neutralized by topical serial ozone/oxygen exposure. Organisms such as Candida, Aspergillus, Histoplasma and Cryptococcus, among others, typically resistant to anti-fungal agents, invariably succumb to serial topical ozone treatments.

Typically, when cultured, an infected wound may yield a dozen or more bacterial and fungal families. No antibiotic can inactivate such a wide spectrum of microorganisms. Ozone, on the other hand, knows no such resistance because it functions on mechanisms of oxidative challenge. This fact is especially relevant in the current age of MRSA, multidrug resistant bacteria (MDR), and NDM-1.

In the clinical practice of topical ozone/oxygen therapy, each case must be carefully evaluated relative to etiology and stage of the pathogenic process. Dosage and frequency of ozone administration are individually calibrated and are subject to change as treatment advances. Finally, integration of this therapy into the fabric of a multidisciplinary approach is essential for clinical success.

This specialized medical technology recruits the remarkable capacity of oxygen/ozone mixtures for inactivating all manner of bacterial and fungal families that colonize wounds: diabetic skin ulcers, decubitus and vascular ulcers, surgical wounds, poorly healing wounds, amputations, complex accident and war wounds, infected burns, frostbite, infected lymphedema, pre-gangrenous lesions and dermal injuries secondary to radiation exposure are all candidates for this innovative, effective, and yet relatively unexplored therapy.

Adjunctive topical ozone/oxygen treatment invokes a concept of concurrent administration of this therapy with other modalities, whether surgical, antibiotic, and even hyperbaric. Emergency topical ozone/oxygen treatment, in the context of other measures, may be limb-saving, and even life-saving, when applied in the very first stages of MRSA and MDR infections (e.g., necrotizing fasciitis). Finally, preventive ozone/oxygen may be applied to forestall the development of infectious processes in cases that present high likelihood of this outcome (e.g., complex traumatic injuries, war wounds).

The FDA has already approved topical oxygen for the treatment of diabetic ulcers, decubitus ulcers, and vascular skin lesions. This technology adds another ingredient, ozone, in small yet vital concentrations, lending its potent antimicrobial action, toxin-neutralization, biofilm destruction, and vascularization-stimulating properties, to the mission of wound healing in a wide spectrum of clinical conditions.