La Fine dell'Era degli Antibiotici? Una Nuova Speranza Arriva dall'Ozono

Immaginate un mondo dove un piccolo taglio infetto o una ferita chirurgica non guariscano, perché  i farmaci che per decenni hanno salvato milioni di vite, gli antibiotici, non funzionano più. Non è  uno scenario da film di fantascienza, ma un'allarmante realtà che stiamo già affrontando. Si chiama  resistenza antimicrobica (AMR), ed è stata definita dall'Organizzazione Mondiale della Sanità  come una delle maggiori minacce per la salute globale.  

Ma cosa succede se gli antibiotici falliscono? La medicina sta cercando nuove strade, e una di  queste potrebbe essere sorprendentemente antica: l'ozonoterapia.  

La Grande Sfida della Resistenza agli Antibiotici  

Il problema della resistenza non è una novità. Già nel 1945, il scopritore della penicillina, Alexander  Fleming, aveva messo in guardia contro l'uso indiscriminato del farmaco, prevedendo che i batteri  avrebbero sviluppato meccanismi per resistergli. E purtroppo, aveva ragione.  

Negli ultimi decenni, l'uso massiccio e non sempre appropriato degli antibiotici, non solo in  medicina ma anche nell'agricoltura e nell'industria, ha accelerato l'evoluzione dei batteri. Hanno  imparato a proteggersi, a disattivare i farmaci e a "pomparli" fuori dalle loro cellule. Il risultato?  Molte infezioni, soprattutto quelle dei tessuti molli (come celluliti e ascessi), sono diventate  estremamente difficili da curare. 

Inoltre, gli antibiotici sistemici (presi per bocca o per via endovenosa) spesso non riescono a  raggiungere le aree infette in modo efficace. Questo accade perché l'infiammazione e il gonfiore  riducono il flusso sanguigno locale, impedendo al farmaco di arrivare dove serve.  

Ozono: Un'Arma Potente e "Senza Scampo" per i Batteri  

L'ozono medico, una miscela di ossigeno e ozono (O2-O3), sta emergendo come una potenziale  soluzione. E il suo più grande vantaggio è che i batteri non possono sviluppare una resistenza  contro di esso.  

Il motivo è semplice: mentre gli antibiotici agiscono bloccando processi vitali specifici dei batteri,  l'ozono attacca le loro cellule in modo diretto e brutale. Il suo potente effetto ossidante distrugge la  parete cellulare del batterio, letteralmente "bucandola" e causandone la morte. È un meccanismo  così universale che i batteri non hanno modo di adattarsi.  

Inoltre, a differenza degli antibiotici, l'ozonoterapia viene somministrata localmente. Questo  permette di concentrare l'azione disinfettante esattamente dove serve, superando i limiti di  circolazione sanguigna delle zone infette. 

La Nostra Esperienza Preliminare: Sette Casi di Successo  

Per valutare il potenziale di questa terapia, abbiamo documentato i risultati ottenuti in sette pazienti  con infezioni dei tessuti molli che non rispondevano ai trattamenti antibiotici convenzionali.  Abbiamo utilizzato l'ozono in diverse modalità, a seconda della patologia:  

• Infezioni diffuse (cellulite): Abbiamo effettuato infiltrazioni sottocutanee radiali per  diffondere l'ozono nell'area infiammata. 

• Ascessi: Abbiamo insufflato la miscela di gas direttamente nella cavità dell'ascesso, dopo  averlo drenato con un catetere. 

• Fistole e infezioni post-chirurgiche: Abbiamo iniettato l'ozono sia all'interno del percorso  fistoloso che attorno alla zona interessata. 

In tutti i casi, abbiamo osservato un notevole miglioramento clinico. I segni di infezione e  infiammazione sono diminuiti progressivamente, portando in alcuni casi a una completa  risoluzione del problema. 

Conclusioni: L'Ozono come "Partner" degli Antibiotici  

Sebbene il nostro studio sia preliminare e basato su un piccolo numero di casi, i risultati sono  estremamente incoraggianti. L'ozonoterapia si è dimostrata un'opzione terapeutica efficace e sicura,  in grado di risolvere infezioni complesse che gli antibiotici da soli non riuscivano a curare.  

L'ozono non deve essere visto come un "sostituto" degli antibiotici, ma piuttosto come uno  strumento complementare. In un'epoca in cui la resistenza antimicrobica rappresenta una minaccia  sempre più concreta, l'ozonoterapia può essere un'arma preziosa per supportare e, in alcuni casi,  sostituire i trattamenti convenzionali, aprendo la strada a nuove strategie per la gestione delle  infezioni difficili.  

Questa esperienza clinica suggerisce la necessità di ulteriori studi sistematici e trial clinici per  confermare il ruolo dell'ozonoterapia e per standardizzare i protocolli di trattamento. L'ozono  potrebbe essere una parte fondamentale della soluzione per affrontare la sfida della resistenza  antimicrobica, assicurando che le infezioni continuino a essere curabili anche in futuro.  

References  

• 1 Fleming’s Discovery of Penicillin. American Chemical Society. Available online: https://www.acs.org/education/what- ischemistry/landmarks/flemingpenicillin.html (accessed on 18  June 2025).  

^• 2 Fleming A. Nobel Lecture: Penicillin. The Nobel Prize. Available online: https://www.nobelprize.org/prizes/medicine/1945/flem- ing/lecture/ (accessed on 18 June 2025).  ^• 3 Urban-Chmiel R, Marek A, Stępień-Pyśniak D, et al. Antibiotic Resistance in Bacteria—A Review. Antibiotics 2022, 11, 1079. https://doi.org/10.3390/antibiotics11081079.  

• 4 Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022; 399: 629-655. https://doi.org/10.1016/  S0140-6736(21)02724-0.  

^• 5 Smith R, Coast J. The true cost of antimicrobial resistance. BMJ 2013, 346, f1493. https://core.ac.uk/reader/13116679.  

^• 6 Marston DH, Dixon MD, Knisely MJ., et al. Antimicrobial Resistance. JAMA. 2016; 316: 1193-1204.  

• 7 World Health Organization (WHO). Antimicrobial Resistance. Fact Sheet November 2023. Available online: https://www. who.int/news-room/fact-sheets/detail/antimicrobial resistance (accessed on 18 June 2025).  

^• 8 Fernández-Villa D, Aguilar MR, Rojo L. Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications. Int. J. Mol. Sci. 2019; 20: 4996.  ^• 9 Kapoor G, Saigal S, Elongavan A. Action and resistance mechanisms of antibiotics: A guide for clinicians. J. Anaesthesiol. Clin. Pharmacol. 2017; 33: 300-305.  

• 10 ReAct - Action on Antibiotic Resistance. Resistance Mechanisms in Bacteria. ReAct Toolbox. Available online: https://www.reactgroup.org/toolbox/understand/antibiotic- resistance/ resistance-mechanisms-in-bacteria/ (accessed on 18 June 2025).  

^• 11 Fair JR, Tor Y. Antibiotics and Bacterial Resistance in the 21st Century. Perspect. Med. Chem. 2014; 6: 25-64. https://doi. org/10.4137/PMC.S14459  

• 12 Salam A, Al-Amin Y, Salam TM, et al. Antimicrobial Resistance: A Growing Serious Threat for Global Public Health. Healthcare. 2023; 11: 1946. https://doi.org/10.3390/ healthcare11141946  

^• 13 O’Neill J. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations; Review on Antimicrobial Re- sistance: London, UK, 2014. 

^• 14 Reardon S. WHO warns against ‘post-antibiotic’ era. Nature. 2014; 244: 1356-1357. https://doi.org/10.1038/ nature.2014.15135  

• 15 Murugaiyan J, Kumar PA, Rao GS, et al. Progress in Alternative Strate-gies to Combat Antimicrobial Resistance: Focus on Antibiotics. Antibiotics. 2022; 11: 200. https://doi.org/ 10.3390/ antibiotics11020200  

^• 16 BoL,SunH,LiY-D,etal.CombatingAntimicrobialResistance: The Silent War. Front. Pharmacol. 2024; 15: 1347750. https:// doi.org/10.3389/fphar.2024.1347750  

• 17 Centers for Disease Control and Prevention (CDC). Preventing Antimicrobial Resistance. Available online: https://www.cdc. gov/antimicrobial-resistance/prevention/index.html  (accessed on 18 June 2025).  

• 18 European Centre for Disease Prevention and Control (ECDC). Directory of Guidance for the Prevention and Control of Anti- microbial Resistance. Available online: https:// www.ecdc. europa.eu/en/publications-data/directory-guidance-prevention- and-control/antimicrobial-resistance-strategies (accessed on 18 June 2025).  

• 19 World Health Organization (WHO). Antimicrobial Resistance. Fact Sheet. Available online: https://www.who.int/news-room/ fact-sheets/detail/antimicrobial-resistance (accessed on  18 June 2025).  

• 20 Annunziato G. Strategies to Overcome Antimicrobial Resistance (AMR) Making Use of Non-Essential Target Inhibitors: A Review. Int. J. Mol. Sci. 2019; 20: 5844. https:// doi.org/ 10.3390/ijms20235844  

• 21 Mai-Prochnow A, Murphy AB, McLean KM, et al. Atmospheric Pressure Plasmas: Infection Con-trol and Bacterial Responses. Int. J. Antimicrob. Agents 2014; 43: 508-517. https:// doi. org/10.1016/j.ijantimicag.2014.01.025  

• 22 Bouza E, Burillo A. Current International and National Guidelines for Managing Skin and Soft Tissue Infections. Curr. Opin. Infect. Dis. 2022; 35: 61-71. https://doi.org/10.1097/  QCO.0000000000000814  

• 23 Stevens LD, Bisno LA, Chambers FH, et al. Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases  Society of America. Clin. Infect. Dis. 2015; 60: 1448. https://doi. org/10.1093/cid/civ114  

• 24 Duane TM, Huston JM, Collom M, et al. Surgical Infection Society 2020 Updated Guidelines on the Management of Complicated Skin and Soft Tissue In-fections. Surg. Infect.  (Larchmt). 2021; 22: 383-399. https://doi.org/10.1089/ sur.2020.436  

^• 25 Bowler PG. Wound Pathophysiology, Infection and Therapeutic Options. Ann. Med. 2002; 34: 419-427. https://doi. org/10.1080/078538902321012360  

• 26 Brook I. Abscesses. In Polymicrobial Diseases; Brogden, K.A., Guthmiller, J.M., Eds, ASM Press: Washington, DC, USA, 2002; Chapter 9. Available online: https:// www.ncbi.nlm.nih. gov/books/NBK2497/ (accessed on 18 June 2025).  

• 27 Ki V, Rotstein C. Bacterial Skin and Soft Tissue Infections in Adults: A Review of Their Epidemiology, Pathogenesis, Diag-nosis, Treatment and Site of Care. Can. J. Infect. Dis.  Med. Microbiol. 2008; 19: 173-184. https://doi. org/10.1155/2008/846453  

• 28 Sartelli M, et al. 2018 WSES/SIS-E Consensus Conference: Recommendations for the Management of Skin and Soft-Tissue Infections. World J. Emerg. Surg. 2018; 13: 58. https:// doi. org/10.1186/s13017-018-0219-9  

• 29 Ubhi D. Skin and Soft Tissue Infections: What You Need to Know. ID Care Blog, 20 August 2021. Available online: https:// idcare.com/blog/skin-and-soft-tissue-infections-what you- need-to-know/ (accessed on 18 June 2025).  

• 30 Le J. Drug Distribution to Tissues. Merck Manuals Professional Edition. Available online: https://www.merckmanuals.com/ professional/clinical-pharmacology/pharmacokinetics/ drug- distribution-to-tissues (ac-cessed on 18 June 2025).  

• 31 De Sutter P-J, Hermans E, De Cock P, et al. Penetration of Antibiotics into Subcu-taneous and Intramuscular Interstitial Fluid: A Meta-Analysis of Microdialysis Studies in Adults.  Clin. Pharmacokinet. 2024; 63: 965-980. https://doi.org/10.1007/ s40262-024-01394-z  

• 32 Jager NGL, van Hest RM, Lipman J, et al. Antibiotic Exposure at the Site of Infection: Principles and Assessment of Tissue Penetration. Expert Rev. Clin. Pharmacol. 2019; 12:  623-634. https://doi.org/10.1080/17512433.2019.1621161  

• 33 ReAct - Action on Antibiotic Resistance. Resistance Mechanisms in Bacteria. Available online: https://www.reactgroup. org/toolbox/understand/antibiotic-resistance/resistance mechanisms-in-bacteria/ (accessed on 18 June 2025).  

• 34 Rajput P, Nahar KS, Rahman KM. Evaluation of Antibiotic Resistance Mechanisms in Gram-Positive Bacteria. Antibiot- ics 2024; 13: 1197. https://doi.org/10.3390/ antibiotics13121197  

• 35 Mlynarczyk-Bonikowska B, Kowalewski C, Krolak-Ulinska A, et al. Molecular Mechanisms of Drug Resistance in Staphylococcus aureus. Int. J. Mol. Sci. 2022; 23: 8088. https://  doi.org/10.3390/ijms23158088 

• 36 Huemer M, Mairpady Shambat S, Brugger SD, et al. Antibiotic Resistance and Persistence—Implications for Human Health and Treatment Perspectives. EMBO Rep. 2020; 21:  e51034. https://doi.org/10.15252/embr.202051034  

• 37 Pray L. Antibiotic Resistance, Mutation Rates and MRSA: A Natural Innate AMR. Nature Educ. 2008, 1, 30. Available online: https://www.cdc.gov/antimicrobial-resistance/data research/threats/index.html (accessed on 18 June 2025).  

66  

Ozone therapy a supportive tool to face the anti microbial re-sistance in the treatment of soft tissue infection Amato De Monte  

^• 38 Ozone for Disinfection. Available online: https://bit. ly/4di6DHm (accessed on 18 June 2025).  

^• 39 Absolute Ozone. Ozone vs Chlorine for Water Disinfection. Available online: https://absoluteozone.com/ozone-vs-chlorine- for-water-disinfection/ (accessed on 18 June 2025).  

• 40 RCM - Clean Ozone Energy. Is There Zero Impact Cleaning? Available online: https://www.rcm.it/en/blog/clean-ozone- energy-is-there-zero-impact-cleaning/ (accessed on 18 June  2025).  

^• 41 Ozone Disinfection Australia. How Ozone Works. Available online: https://www.ozonedisinfection.com.au/how-ozone- works/ (accessed on 18 June 2025).  

• 42 Oxidation Technologies. Exploring Oxidation: Understanding How Ozone Works as a Powerful Oxidizing Agent. Availa- ble online: https://www.oxidationtech.com/blog/exploring oxidation-understanding-how-ozone-works-as-a-powerful- oxidizing-agent/ (accessed on 18 June 2025).  

_• ^{43 ECO}₃. Ozone Facts. Available online: https://www.eco3.co.za/ Ozone_Facts.htm (accessed on 18 June 2025).  

^• 44 Oxidation Technologies. Ozone Basics - Oxidation. Available online: https://www.oxidationtech.com/ozone/ozone-basics/ oxidation (accessed on 18 June 2025).  

• 45 Loeb LB, Thompson MC, Drago J, et al. Worldwide Ozone Capacity for Treatment of Drinking Water and Wastewater: A Review. Ozone Sci. Eng. 2012; 34: 64-77. https://doi.org/ 10.10 80/01919512.2012.640251  

• 46 Domenjoud B, Tatari T, Esplugas T, et al. Ozone-Based Processes Applied to Municipal Secondary Effluents. Ozone Sci. Eng. 2011; 33: 64-77. https://doi.org/10.1080/01919512.20  12.640251  

• 47 CORDIS. New Technology Provides Clean Water in Africa. Available online: https://cordis.europa.eu/article/id/415837- new-technology-provides-clean-water-in-africa/it (accessed  on 18 June 2025).  

• 48 Gruppo EcoEridania. Il più grande depuratore al mondo è in Egitto. Available online: https://gruppoecoeridania.com/il-piu- grande-depuratore-al-mondo-e-in-egitto/ (accessed on 18  June 2025).  

• 49 Market Research Intellect. Global Ozone Water Treatment System Market Size, Trends and Projections. Report ID: 1067752, Published: December 2024. Available online: https://  www.marketresearchintellect.com/product/ozone-water- treatment-system-market/ (accessed on 18 June 2025).  

• 50 Ranerelli T. Ozono in porcilaia, meno farmaci e più guadagno. Suinicoltura - Edagricole, 10 May 2018. Available online: https://suinicoltura.edagricole.nelcampo.it/ (accessed on 18  June 2025).  

^• 51 Moore G, Griffith C, Peters,A. Bactericidal Properties of Ozone and Its Potential Application as a Terminal Disinfectant. J. Food Prot.  

^• 52 Fontes B, et al. BMC Infectious Diseases 2012, 12, 358. https:// doi.org/10.1186/1471-2334-12-358  

^• 53 Rangel K, Cabral FO, Lechuga CG, et al. Detrimental Effect of Ozone on Pathogenic Bacteria. Microorganisms 2021, 10, 40. https://doi.org/10.3390/microorganisms10010040  

• 54 Westover C, Rahmatulloev S, Danko D, et al. Ozone Disinfection for Elimination of Bacteria and Degradation of SARS-CoV-2 RNA for Medical Environments. Genes 2023; 14: 85.  https://doi.org/10.3390/genes14010085  

• 55 Marshalein A, Satyalakshmi M, Satyanath D, et al. Efficacy of Ozone Therapy as an Antibacterial Agent: A Narrative Review. Res. J. Med. Sci. 2023; 17: 455-462. https://doi.org/ 10.59218/ makrjms.2023.455.462  

^• 56 Song M, Zeng Q, Xiang Y, et al. The Antibacterial Effect of Topical Ozone on the Treatment of MRSA Skin Infection. Mol. Med. Rep. 2018; 17: 2449-2455. 

^• 57 Thanomsub B, Anupunpisit V, Chanphetch S, et al. Effects of Ozone Treat-ment on Cell Growth and Ultrastructural Changes in Bacteria.  ^• 58 Sharma M, Hudson JB. Ozone Gas Is an Effective and Practical Antibacterial Agent. Am. J. Infect. Control. 2008; 36: 559-563. https://doi.org/10.1016/j.ajic.2007.10.021  ^• 59 Rangel K, Cabral FO, Lechuga GC, et al. Detrimental Effect of Ozone on Pathogenic Bacteria. Microorganisms. 2021; 10: 40. https://doi.org/10.3390/microorganisms10010040  ^• 60 Gu YQ, Ning GH. Health Care Functions of Ozone Sterilizer. Glob. J. Med. Clin. Case Rep. 2023; 10: 027-030. https://doi. org/10.17352/2455-5282.000174  ^• 61 Bonetti M. Trattato di Ossigeno-Ozono Terapia; Piccin Nuova Libreria: Padova, Italy, 2024. ISBN 978-299-3468-3.  

^• 62 Zambello A, Bonetti M. Ozonoterapia. Manuale Pratico; Ed. Fedan SA, 2019. ISBN 889461400X.  

• 63 Hidalgo-Tallón FJ, Torres-Morera LM, Baeza-Noci J, et al. Updated Review on Ozone Therapy in Pain Medicine. Front. Physiol. 2022; 13: 840623. https://doi.org/10.3389/  fphys.2022.840623  

• 64 Jeyaraman M, Jeyaraman N, Ramasubramanian S, et al. Ozone Therapy in Musculoskeletal Medicine: A Comprehensive Review. Eur. J. Med. Res. 2024; 29: 398. https://doi. org/ 10.1186/s40001-024-01976-4  

^• 65 Cleveland Clinic. Ozone Therapy. Available online: https:// health.clevelandclinic.org/ozone-therapy (accessed on 18 June 2025).  

^• 66 Chansoria M, Saluja SK, Verma A, et al. Ozone in Pain Medicine - Modern-day Asclepius. Indian J. Pain. 2025; 39: 4-10. https://doi.org/10.4103/ijpn.ijpn_41_24  ^• 67 Jandura J, Vajda M, Cech M, et al. Oxygen-Ozone Therapy of Musculoskeletal Neck Pain: A Review. J. Pers. Med. 2024; 14: 326. https://doi.org/10.3390/jpm14030326  

• 68 Bonetti M, Ottaviani GM, Simonetti L, et al. Treatment of Low- Back Pain With Oxy-gen-Ozone Therapy. In Hernia Updates and Approaches; IntechOpen: London, UK, 2023.  https://doi. org/10.5772/intechopen.1001902  

• 69 Rimeika G, Bonetti M, Saba L, et al. Metanalysis on the Effec- tiveness of Low Back Pain Treatment with Oxygen-Ozone Mixture: Comparison between Image-Guided and Non Image- Guided Injection Techniques. Eur. J. Radiol. Open. 2021; 8: 10038.  

• 70 Viebahn-Hänsler R, León Fernández OS, Fahmy Z. Ozone in Medicine: Clinical Evaluation and Evidence Classification of the Systemic Ozone Applications, Major  Autohemotherapy and Rectal Insufflation, According to the Requirements for Evi- dence-Based Medicine. Ozone Sci. Eng. 2016; 38: 322-345. https://doi.org/ 10.1080/01919512.2016.1191992  

• 71 Viebahn-Haensler R, León Fernández OS. Ozone in Medicine: The Low-Dose Ozone Concept and Its Basic Biochemical Mechanisms of Action in Chronic Inflammatory Diseases.  Int. J. Mol. Sci. 2021; 22: 7890. https://doi.org/10.3390/ ijms22157890  

^• 72 Clavo B, Pérez LJ, López L, et al. Effect of Ozone Therapy on Muscle Oxygenation. J. Altern. Complement. Med. 2003; 9: 251-256.  

• 73 Clavo B, Borrelli E. Editorial: Ozone in Medicine: Biochemical Background, Physiological Modulation and Clinical Ap- plications. Front. Physiol. 2023; 14: 1112860. https://doi.  org/10.3389/fphys.2023.1112860  

• 74 Clavo B, Santana-Rodríguez N, Llontop P, et al. Ozone Therapy as Adjuvant for Cancer Treatment: Is Further Research Warranted? Evid.-Based Com-plement. Altern. Med. 2018;  2018: 7931849. https://doi.org/10.1155/2018/7931849  

• 75 Bocci V, Zanardi I, Travagli V. Ozone: A New Therapeutic Agent in Vascular Diseases. Am. J. Cardiovasc. Drugs. 2011; 11: 73-82. https://doi.org/ 10.2165/11539890-000000000-00000  

_• ^{76 Juchniewicz H, Lubkowska A. Oxygen-Ozone (O}₂^-O₃) Therapy in Peripheral Arterial Disease (PAD): A Review Study. Ther. Clin. Risk Manag. 2020; 16: 579-594. https://doi.org/ 10.2147/ TCRM.S255247  

• 77 Pandolfi S, Chirumbolo S, Franzini M, et al. Oxygen-Ozone Therapy for Myocardial Ischemic Stroke and Cardiovascular Disorders. Med. Gas Res. 2025; 15: 36-43. https://doi. org/ 10.4103/mgr.MEDGASRES-D-23-00013  

^• 78 Bocci V. Ozone: A New Medical Drug; Springer: Dordrecht, The Netherlands, 2005; ISBN 1-4020-3140-8.  

^• 79 Borrelli E, De Monte A, Bocci V. Oxygen Ozone Therapy in the 

67  

Ozone therapy a supportive tool to face the anti microbial re-sistance in the treatment of soft tissue infection Amato De Monte  

Integrated Treatment of Chronic Ulcer: A Case Series Re-port.  

Int. J. Recent Sci. Res. 2015; 6: 4132.  

^• 80 Liu L, Zeng L, Gao L, et al. Ozone Therapy for Skin Diseases:  

Cellular and Molecular Mechanisms. Int. Wound J. 2023; 20:  

2376-2385. https://doi.org/10.1111/iwj.14060  

^• 81 Roth A, Krishnakumar A. Ozone as a Topical Treatment for  

Infected Dermal Wounds. Front. Biosci. (Elite Ed) 2023; 15: 9.  

https://doi.org/10.31083/j.fbe1502009  

^• 82 Nabi BN, Sedighinejad A, Mirbolouk AR, et al. The  

Effectiveness of Ozone Therapy in Chronic Osteomyelitis: A Randomized Controlled Clinical Trial. Arch. Clin. Infect. Dis. 2018; 13: e61320. https://doi.org/10.5812/archcid.61320  ^• 83 ZengJ,LuJ.MechanismsofActionInvolvedinOzone-Therapy in Skin Diseases. Int. Immunopharmacol. 2018; 56: 235-241.  

^• 84 Matos LI, Rodríguez EJ, Maydelin L, et al. Adjuvant Ozone Therapy in Necrotizing Soft Tissue Infec-tion: Presentation of a Case. MediSur. 2024; 22: 341-348.  

• 85 Marinova P. The Effect of Topical Application with Ozoile as a Novel Method in the Complex Treatment of Soft Tissue In- fections and Chronic Wounds. Trakia J. Sci. 2023,  (September). https://doi.org/10.15547/tjs.2023.03.005  

86 Roth A, Maruthamuthu MK, Nejati S, et al. Wearable Adjunct Ozone and Antibiotic Therapy System for Treatment of Gram- Negative Dermal Bacterial Infection. Sci. Rep. 2022; 12: 13927. https:// doi.org/10.1038/s41598-022-17495-.