10.3390/polym8030084

Vollständiger Abstract

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<b>Background/Objectives:</b> Antimicrobial resistance (AMR) represents one of the greatest challenges to modern medicine, particularly in chronic infections sustained by multidrug-resistant (MDR) pathogens and biofilm formation. SIOOT ® Oxygen-ozone major autohemotherapy (SIOOT ® -O 2 -O 3 -MAHT) has been proposed as an adjunctive treatment capable of exerting direct antimicrobial, antibiofilm, and immunomodulatory effects. This pilot study evaluated the clinical, microbiological, inflammatory, and mechanistic effects of standardized SIOOT ® -O 2 -O 3 -MAHT administered alongside conventional antibiotic therapy in patients with chronic MDR bacterial infections. <b>Methods:</b> A prospective longitudinal pilot study was conducted in 257 patients with chronic infectious and inflammatory disorders refractory to prolonged antibiotic treatment. Patients received standardized SIOOT ® -O 2 -O 3 -MAHT according to protocols from the Italian Scientific Society of Oxygen-Ozone Therapy (SIOOT) in addition to guideline-directed antibiotics. Longitudinal bacterial burden (CFU/mL), culture positivity, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were all assessed over a 12-month follow-up. In parallel, macrophage phagocytosis, intracellular bacterial killing, phago-lysosomal maturation, and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) biofilm disruption were investigated using confocal laser scanning microscopy, gentamicin protection assays, and scanning electron microscopy. <b>Results:</b> SIOOT ® -O 2 -O 3 -MAHT was associated with a progressive reduction in bacterial burden from a geometric mean of 6.43 × 10 6 CFU/mL before treatment to complete microbiological clearance after one year. Mean bacterial reduction reached 98.53% after one week and 99.95% after one month, while culture positivity decreased from 100% to 0% by one year (all <i>p</i> < 0.0001). ESR normalization increased from 28.2% at one week to 98.1% at one year, and CRP normalization increased from 32.4% to 98.7%. Mechanistic analyses demonstrated significantly enhanced macrophage phagocytosis, phago-lysosomal maturation, intracellular MRSA killing, and marked disruption of mature MRSA biofilms following ozone treatment. <b>Conclusions:</b> Adjunctive SIOOT ® -O 2 -O 3 -MAHT was associated with reductions in bacterial burden, progressive improvement of systemic inflammatory markers, enhanced macrophage antimicrobial activity, and disruption of bacterial biofilms in patients with chronic multidrug-resistant infections. Given the prospective, non-randomized pilot design, these findings should be considered exploratory and hypothesis-generating, providing biological and clinical rationale for further investigation. Adequately powered randomized controlled trials are required to determine the efficacy, safety, and long-term clinical benefits of adjunctive oxygen-ozone therapy.

Abstract: PubMed · Datensatz