{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:31:36Z","timestamp":1785335496353,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,17]],"date-time":"2025-05-17T00:00:00Z","timestamp":1747440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Necrotizing soft tissue infection (NSTI) is a life-threatening, high morbidity pathology that requires aggressive, multidisciplinary management. Surgery and antibiotic administration are core components of treatment. Adjunctive incorporation of hyperbaric oxygen therapy (HBOT) can further enhance treatment and recovery. Benefit is achieved through multiple effects brought about by increase of local and systemic oxygen tension. Direct effects include bacteriostasis, disruption of bacterial toxin production, and attenuation of inflammation. Indirect benefits include demarcation of viable tissue to enhance surgical efforts, potentiation of antibiotics, and enhancement of immune system function. Overall, HBOT has few contraindications and is typically well tolerated by patients. Treatment course and appropriateness of individual patients can be determined through consultation with Hyperbaric Medicine specialists. The benefits of HBOT in morbidity and mortality of NSTI have been well demonstrated and this therapy should be considered as a component of care to all affected patients.<\/jats:p>","DOI":"10.3390\/jcm14103511","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T06:31:29Z","timestamp":1747636289000},"page":"3511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Role of Hyperbaric Oxygen Therapy in Management of Necrotizing Soft Tissue Infection"],"prefix":"10.3390","volume":"14","author":[{"given":"Thomas J.","family":"Gregory","sequence":"first","affiliation":[{"name":"R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinjal","family":"Sethuraman","sequence":"additional","affiliation":[{"name":"R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1007\/s00134-019-05730-x","article-title":"Patient\u2019s characteristics and outcomes in necrotising soft-tissue infections: Results from a Scandinavian, multicentre, prospective cohort study","volume":"45","author":"Madsen","year":"2019","journal-title":"Intensiv. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Smolle, C., Lindenmann, J., Kamolz, L., and Smolle-Juettner, F.M. (2021). The History and Development of Hyperbaric Oxygenation (HBO) in Thermal Burn Injury. Medicina, 57.","DOI":"10.3390\/medicina57010049"},{"key":"ref_3","unstructured":"Huang, E. (2023). UHMS Hyperbaric Medicine Indications Manual, Best Publishing. [15th ed.]."},{"key":"ref_4","unstructured":"Bennett, M.H., Mitchell, S.J., Buckey, J.C., and Robins, M. (2023). Emerging Indications. Hyperbaric Medicine Indications Manual, Best Publishing Company. [15th ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1111\/j.1749-6632.1964.tb56316.x","article-title":"Considerations on hyperbaric oxygen therapy at three atmospheres absolute for clostridial infections type welchii","volume":"117","author":"Brummelkamp","year":"1965","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1089\/sur.2012.135","article-title":"Not just full of hot air: Hyperbaric oxygen therapy increases survival in cases of necrotizing soft tissue infections","volume":"15","author":"Shaw","year":"2014","journal-title":"Surg. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1177\/0310057X1504300604","article-title":"Necrotising soft tissue infections: The effect of hyperbaric oxygen on mortality","volume":"43","author":"Devaney","year":"2015","journal-title":"Anaesth. Intensive Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13017-022-00448-6","article-title":"Outcome of necrotizing fasciitis and Fournier\u2019s gangrene with and without hyperbaric oxygen therapy: A retrospective analysis over 10 years","volume":"17","author":"Mladenov","year":"2022","journal-title":"World J. Emerg. Surg."},{"key":"ref_9","unstructured":"Neuman, T.S., and Thom, S.R. (2008). Physics of Hyperbaric Oxygen Therapy in Physiology and Medicine of Hyperbaric Oxygen Therapy E-Book, Elsevier Health Sciences."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1067\/j.cpsurg.2014.06.001","article-title":"Necrotizing soft tissue infections: Review and current concepts in treatment, systems of care, and outcomes","volume":"51","author":"Hakkarainen","year":"2014","journal-title":"Curr. Probl. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.tim.2022.01.002","article-title":"The battle for oxygen during bacterial and fungal infections","volume":"30","author":"Laborde","year":"2022","journal-title":"Trends Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.biopha.2018.10.142","article-title":"Hyperbaric oxygen therapy: Antimicrobial mechanisms and clinical application for infections","volume":"109","author":"Memar","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1038\/nrmicro1004","article-title":"Antimicrobial reactive oxygen and nitrogen species: Concepts and controversies","volume":"2","author":"Fang","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jss.2008.08.031","article-title":"Hyperbaric oxygen as adjunctive therapy in experimental mediastinitis","volume":"155","author":"Turhan","year":"2009","journal-title":"J. Surg. Res."},{"key":"ref_15","first-page":"169","article-title":"Therapy with hyperbaric oxygen and cefazolin for experimental osteomyelitis due to Staphylococcus aureus in rats","volume":"26","author":"Mendel","year":"1999","journal-title":"Undersea Hyperb. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ijantimicag.2015.12.005","article-title":"Reinforcement of the bactericidal effect of ciprofloxacin on Pseudomonas aeruginosa biofilm by hyperbaric oxygen treatment","volume":"47","author":"Kolpen","year":"2016","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.ijantimicag.2017.04.025","article-title":"Hyperbaric oxygen therapy augments tobramycin efficacy in experimental Staphylococcus aureus endocarditis","volume":"50","author":"Lerche","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E2100","DOI":"10.1073\/pnas.1401876111","article-title":"Antibiotics induce redox-related physiological alterations as part of their lethality","volume":"111","author":"Dwyer","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12147","DOI":"10.1073\/pnas.1203735109","article-title":"Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals","volume":"109","author":"Grant","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/j.drudis.2022.03.015","article-title":"Unraveling antimicrobial resistance using metabolomics","volume":"27","author":"Kok","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"300","DOI":"10.4103\/joacp.JOACP_349_15","article-title":"Action and resistance mechanisms of antibiotics: A guide for clinicians","volume":"33","author":"Kapoor","year":"2017","journal-title":"J. Anaesthesiol. Clin. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e950163","DOI":"10.4161\/15384101.2014.950163","article-title":"Human polymorphonuclear neutrophils specifically recognize and kill cancerous cells","volume":"3","author":"Yan","year":"2014","journal-title":"Oncoimmunology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1128\/iai.9.2.337-341.1974","article-title":"Bactericidal activity of aerobic and anaerobic polymorphonuclear neutrophils","volume":"9","author":"Mandell","year":"1974","journal-title":"Infect. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.lfs.2013.06.003","article-title":"Effects of hyperbaric oxygen treatment on antimicrobial function and apoptosis of differentiated HL-60 (neutrophil-like) cells","volume":"93","author":"Almzaiel","year":"2013","journal-title":"Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1136\/jim-2021-001837","article-title":"Hyperbaric oxygen treatment impacts oxidative stress markers in patients with necrotizing soft-tissue infection","volume":"69","author":"Hedetoft","year":"2021","journal-title":"J. Investig. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1172\/JCI32730","article-title":"Heme oxygenase-1-derived carbon monoxide enhances the host defense response to microbial sepsis in mice","volume":"118","author":"Chung","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1056\/NEJM198902093200606","article-title":"Tissue destruction by neutrophils","volume":"320","author":"Weiss","year":"1989","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1089\/wound.2012.0383","article-title":"Neutrophils and Wound Repair: Positive Actions and Negative Reactions","volume":"2","author":"Wilgus","year":"2013","journal-title":"Adv. Wound Care"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Baiula, M., Greco, R., Ferrazzano, L., Caligiana, A., Hoxha, K., Bandini, D., Longobardi, P., Spampinato, S., and Tolomelli, A. (2020). Integrin-mediated adhesive properties of neutrophils are reduced by hyperbaric oxygen therapy in patients with chronic non-healing wound. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0237746"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ryter, S.W. (2020). Therapeutic Potential of Heme Oxygenase-1 and Carbon Monoxide in Acute Organ Injury, Critical Illness, and Inflammatory Disorders. Antioxidants, 9.","DOI":"10.3390\/antiox9111153"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1056\/NEJMra0910283","article-title":"Hypoxia and inflammation","volume":"364","author":"Eltzschig","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.colsurfb.2010.11.019","article-title":"Osmotic phenomena in application for hyperbaric oxygen treatment","volume":"83","author":"Babchin","year":"2011","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Barshtein, G., Pajic-Lijakovic, I., and Gural, A. (2021). Deformability of Stored Red Blood Cells. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.722896"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"104534","DOI":"10.1016\/j.mvr.2023.104534","article-title":"Hyperbaric oxygenation improve red blood cell deformability in patients with acute or chronic inflammation","volume":"148","author":"Steenebruggen","year":"2023","journal-title":"Microvasc. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S1438-4221(00)80074-0","article-title":"The pathogenesis of clostridial myonecrosis","volume":"290","author":"Stevens","year":"2000","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_36","unstructured":"Buboltz, J.B., and Murphy-Lavoie, H.M. (2025, March 03). Gas Gangrene. [Updated 2023 Jan 30], StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK537030\/."},{"key":"ref_37","first-page":"731","article-title":"Clostridial myonecrosis (gas gangrene)","volume":"39","author":"Bakker","year":"2012","journal-title":"Undersea Hyperb. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1006\/anae.1999.0191","article-title":"The Clostridium perfringens\u03b1-toxin","volume":"5","author":"Titball","year":"1999","journal-title":"Anaerobe"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5204","DOI":"10.1128\/IAI.72.9.5204-5215.2004","article-title":"Effects of Clostridium perfringens alpha-toxin (PLC) and perfringolysin O (PFO) on cytotoxicity to macrophages, on escape from the phagosomes of macrophages, and on persistence of C. perfringens in host tissues","volume":"72","author":"Melville","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1128\/br.26.2_pt_1-2.177-274.1962","article-title":"The histotoxic clostridial infections of man","volume":"26","author":"Maclennan","year":"1962","journal-title":"Bacteriol. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/BF02045889","article-title":"Inhibition of toxin production in Clostridium perfringens in vitro by hyperbaric oxygen","volume":"31","year":"1965","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1001\/archsurg.1966.01330020028004","article-title":"HPO in clostridial toxicity and strangulation obstruction","volume":"93","author":"Nora","year":"1966","journal-title":"Arch. Surg."},{"key":"ref_43","first-page":"1","article-title":"Hyperbaric oxygen in the treatment of gas gangrene and perineal necrotizing fasciitis. A clinical and experimental study","volume":"570","author":"Hirn","year":"1993","journal-title":"Eur. J. Surg. Suppl."},{"key":"ref_44","first-page":"75","article-title":"Experimental and clinical experience with hyperbaric oxygen in the treatment of clostridial myonecrosis","volume":"77","author":"Holland","year":"1975","journal-title":"Surgery"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1001\/archsurg.139.12.1339","article-title":"Hyperbaric oxygen treatment and survival from necrotizing soft tissue infection","volume":"139","author":"Wilkinson","year":"2004","journal-title":"Arch. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"34","DOI":"10.28920\/dhm51.1.34-43","article-title":"Adjunctive hyperbaric oxygen treatment for necrotising soft-tissue infections: A systematic review and meta-analysis","volume":"51","author":"Hedetoft","year":"2021","journal-title":"Diving Hyperb. Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Shishido, A., Schrank, G., Vostal, A., Uehling, M., Tripathi, R., Chintalapati, S., Conway, L., Kus, N., DiChiacchio, L., and Kai, M. (Surg. Infect., 2025). Hyperbaric Oxygen Therapy for Necrotizing Soft Tissue Infections: A Retrospective Cohort Analysis of Clinical Outcomes, Surg. Infect., ahead of print.","DOI":"10.1089\/sur.2024.285"},{"key":"ref_48","unstructured":"Anderson, C.A., and Jacoby, I. (2023). Necrotizing soft tissue infections. Hyperbaric Medicine Indications Manual, Best Publishing Company. [15th ed.]."},{"key":"ref_49","unstructured":"Weening, R.P., Giannakopoulos, G.F., and van Hulst, R.A. (2023). Clostridial myonecrosis (gas gangrene). Hyperbaric Medicine Indications Manual, Best Publishing Company. [15th ed.]."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.yasu.2022.02.011","article-title":"Is There a Place for Hyperbaric Oxygen Therapy?","volume":"56","author":"Sethuraman","year":"2022","journal-title":"Adv. Surg."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Schiavo, S., Brenna, C.T.A., Albertini, L., Djaiani, G., Marinov, A., and Katznelson, R. (2024). Safety of hyperbaric oxygen therapy in patients with heart failure: A retrospective cohort study. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0293484"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1097\/01.ASW.0000508712.86959.c9","article-title":"A Retrospective Analysis of Adverse Events in Hyperbaric Oxygen Therapy (2012\u20132015): Lessons Learned From 1.5 Million Treatments","volume":"30","author":"Barry","year":"2017","journal-title":"Adv. Ski. Wound Care"},{"key":"ref_53","unstructured":"Gengel, K.C., Hendriksen, S., and Cooper, J.S. (2025, May 08). Hyperbaric Related Myopia and Cataract Formation. [Updated 2023 Jul 4], StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK430855\/."},{"key":"ref_54","first-page":"153","article-title":"Hyperbaric and hypobaric chamber fires: A 73-year analysis","volume":"24","author":"Sheffield","year":"1997","journal-title":"Undersea Hyperb. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1016\/S0196-0644(05)80063-0","article-title":"Prevention of hyperbaric-associated middle ear barotrauma","volume":"21","author":"Carlson","year":"1992","journal-title":"Ann. Emerg. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/10\/3511\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:34:19Z","timestamp":1760031259000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/10\/3511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,17]]},"references-count":55,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["jcm14103511"],"URL":"https:\/\/doi.org\/10.3390\/jcm14103511","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,17]]}}}