Post-surgical wounds treated with ozone: a preliminary case series

Dear Editor, Ozone (O3), a molecule consisting of three oxygen atoms, has been widely used in microbiology for various applications. Its strong oxidizing properties make it an effective disinfectant and sanitizer against a wide range of microorganisms, including bacteria, viruses, fungi, and protozoa. The ability of O3 to counteract bacterial growth, somehow indifferently respect to the bacterial species, may represent an opportunity to prevent bacterial colonization of post-surgical wounds particularly upon multidrug resistant (MDR) strains, widely occurring in hospital contexts. MDR bacteria represent a serious concern for public health and the optimal management of hospitals and healthcare services. O3 therapy, by simultaneously eradicating bacteria from infected skin in neighboring post-surgical wounds, may be a possible suggestion to overcome this concern. In one of our preliminary pilot studies, 10 patients, who developed methicillin-resistant Staphylococcus aureus (MRSA; n = 8) or Staphylococcus epidermidis (MRSE; n = 2) infection on various post-surgical wounds, underwent an adjunct therapy with oxygen-ozone (O2-O3) according to a treatment protocol from the Italian Society of Oxygen-Ozone Therapy, once they resorted to our clinic and signed an informed consent according to the Declaration of Helsinki and the Ethical Committee of the Italian Society of Oxygen-Ozone Therapy (Clinica Comunian-SIOOT Prot 5643/04 4-4-2018). Considering that in the present study we expected an anticipated incidence in reducing pain and inflammation by anti-microbial therapy of 90% (group before treatment) and an anticipated incidence in reducing pain and inflammation by O3 of the same entity (90%) (group after treatment), with a type I/II alpha error = 0.05 and a power of 80%, a number of 10 samples is the minimum to reach a sound statistic, in a binomial option "ill-not ill." Cohen's δ test = 0.45929, indicating a medium effect size, which is to be considered a possible initial limitation of this pilot study. Patients underwent an antibiotic panel including most recent antimicrobial drugs for MRSA and MRSE (Table 1) and entered a cycle of O3 adjunct treatments upon failure of the antibiotic therapy. The fundamental rationale of this pilot study comes from evidence reported in literature about the positive outcome reported on microbial and MDR bacterial infections in post-surgical or traumatic wounds following O2-O3 therapy.[1-4]Table 1:: Effect of ozone adjunct therapy on the eradication of MRSA infection on traumatic and post-surgical woundsThe protocol provides for minimum five runs of two weekly O2-O3 autologous blood infusion (O2-O3-MAHT) (50 μg/mL in 200 mL autologous blood), supported with one microinjection per week of 5 μg/mL O3 in situ and/or by rectal O3 insufflation (100 mL of 40 μg/mL O3) and/or topical 5% O3 in a dermatologic formulation. A volume of 200 mL of peripheral blood was withdrawn from any patient by venipuncture, collected in the bag and gently mixed with the prepared O2-O3 mixture (Multiossigen Medical 95 CPSTM), containing 50 μg/mL O3 and within 2 minutes re-introduced into the patient's blood circulation by an intravenous cannula. The application of rectal O3 was excluded for patients showing gut microbiome dysbiosis and rectal pathologies. Its use was recommended in cases of impairments in the mucosal immune response and to enhance the participation of gut microbiome in the immune surveillance. For plasma analytics the relative bias in percent to assess, if bias can be performed in discussing data, was calculated according to the formula: This bias is expressed in relative terms (relative bias), and makes it possible to evaluate the size of the bias due to under-coverage with respect to the true unknown parameter to be estimated. Table 1 summarizes patients' hallmarks before and after the O3 therapy. Following O2-O3-MAHT any inflammation disappeared, cultural investigation[5] resulted in a reduction of at least 2 logs (i.e., 102) CFU/mL (P = 0.00093097, Wilcoxon test) and symptoms disappeared very early, at the second O3 treatment, as biomarkers rapidly normalized their plasma levels. CRP dropped down from 35.21 ± 5.49 mg/dL to 0.37 ± 0.05 mg/dL (−98.95%, P = 0.0007) and ESR from 54.10 ± 19.16 mm/h to 13.10 ± 3.25 mm/h (−75.78%, P = 0.0002). The reduction of the inflammation impact associated with post-traumatic sepsis or bacterial colonization via a specific antimicrobial therapy, failed in all the patients treated before O3 therapy, as continuous relapses in inflammation events and modest reduction in biomarkers (CRP = −16.16%, P = 0.00512, ESR = −10.54%, P = 0.0053), due to MRB (Table 1). Relative bias calculation (STATA software, v.18) and an exemplification of the O2-O3 treatment outcome are reported in Figures 1 and 2.Figure 1:: Calculation of relative bias in percent.Note: Relative bias in percent for C-reactive protein (A) and erythrocyte sedimentation rate (B).Figure 2:: Exemplification of patient 10's chest before (A) and after 2 weeks of oxygen-ozone therapy (B).In this pilot, preliminary study the application of an adjunct treatment with topical and ozonated blood treatment, improved the MRSA-caused inflammation, reducing the bacterial impact and ameliorating patient's ability in restoring his own health. A planned randomized controlled trial with an increased number of patients and controls is under consideration. O3 therapy resulted as a reliable approach to treat patients with post-surgical or traumatic inflamed wounds by MDR bacteria or in case of antibiotic resistance. As MDR is a serious concern in hospitals and healthcare systems, this therapy proposal may be particularly suitable for the many concerns about chronic inflammation ailments due to bacterial-driven chronic inflammation. However, further studies are recommended to improve the impact of this novelty and apply the therapy protocol in the widest way.