Bacterial Infections

Written By Elizabeth Gaffney

HBOT for Bacterial Infections (Anaerobic or Mixed Bacterial Infections)

Introduction

Hyperbaric oxygen therapy (HBOT), in which the patient breathes pure or near-pure oxygen in a pressurised chamber, increases the partial pressure of oxygen in plasma, enhancing oxygen delivery to tissues, augmenting host immune responses, and potentiating antimicrobial therapies. HBOT is an adjunctive therapy for severe or life-threatening bacterial infections, particularly those caused by anaerobic or mixed bacterial flora, such as necrotising soft-tissue infections (NSTIs) (Hedetoft et al., 2021a; Huang et al., 2023), gas gangrene (Rudge, 1993) and Fournier’s gangrene (Raizandha et al., 2022), and refractory osteomyelitis (Savvidou et al., 2018; Hart, 2021). Serious bacterial infections (SBIs) are associated with high morbidity and mortality, and even with early surgical debridement and antibiotic therapy, mortality can exceed 20–30% (Bonne & Kadri, 2017). Adjunctive HBOT may improve patient outcomes when used alongside standard surgical and antimicrobial management.

Benefits of HBOT for Patients with Severe Bacterial Infections

HBOT is used as an adjunct rather than a substitute for standard treatment, and patients with SBIs may experience a range of benefits from HBOT (Memar et al., 2019).

1. Reduced mortality and morbidity: Observational studies and case series suggest that adjunctive HBOT in necrotising infections may be associated with lower mortality compared with standard care alone (Riseman et al., 1990; Huang et al., 2023).

2. Decreased extent of surgical debridement or amputation: HBOT can limit tissue necrosis and reduce the need for radical surgery (Johnson-Arbor, 2023), including amputation, especially in patients with necrotising fasciitis (Riseman et al., 1990; Wilkinson et al., 2004).

3. Improved infection control: HBOT enhances bacterial clearance, particularly of anaerobic organisms, and improves the efficacy of some antibiotics (Çimşit et al., 2009).

Side Effects and Risks of HBOT

HBOT is generally well tolerated, and serious side effects are rare (Camporesi, 2014; Zhang et al., 2023). Reported side effects are typically mild and reversible, including middle ear barotrauma and transient myopia. Serious complications, such as oxygen toxicity seizures or pulmonary barotrauma, are rare. 

Treatment of SBIs can be logistically challenging in unstable or critically ill patients. For example, in some series of necrotising infections, not all eligible patients could undergo HBOT because of haemodynamic instability or other contraindications (Mladenov et al., 2022; Hyldegaard et al., 2025).

HBOT at OxyGeneration

OxyGeneration runs hyperbaric sessions at 2.0 ATA with clients at pressure for a minimum of 60 minutes with approximately 10 minutes at the beginning and end of each session for compression and decompression. The chamber is filled with air, and clients breathe oxygen through a mask. 

Our chamber complies with the Medical Device Regulation and the EN 14931 European Standard (Pressure Vessels for Human Occupancy). We have a strict maintenance schedule and an external third-party maintains and services the chamber and equipment. We manufacture our own oxygen at a purity of 94%–96%, which meets the European definition of HBOT (Kot et al., 2023). Although the US FDA definition specifies 100% oxygen, our chamber and services meet the definition of HBOT according to the European Underwater and Baromedical Society (EUBS) and the European Code of Good Practice (Kot et al., 2023). 

Because OxyGeneration does not use 100% oxygen, clients can self-refer, and no prescription is required. OxyGeneration provides exclusively non-emergency care and does not provide sessions to clients who require medical supervision. 

Mechanisms of Action of HBOT

HBOT may facilitate the resolution of SBIs through several mechanisms, primarily by enhancing oxygen delivery to tissues (Cannellotto et al., 2024): 

1. Inhibition of anaerobic bacterial growth: Many pathogenic anaerobes, including Clostridium perfringens, are inhibited or killed by hyperoxic conditions (Brown et al., 1979; Buboltz & Murphy-Lavoie, 2023). In biofilm-associated infections, increased oxygenation and reactive oxygen species (ROS) may destabilise biofilms and make organisms more vulnerable to antimicrobials and host defences (Jensen et al., 2019).

2. Synergy with antibiotics: HBOT may enhance the efficacy of certain antibiotics, particularly aminoglycosides, fluoroquinolones, and β-lactams, by improving tissue oxygenation and altering bacterial growth kinetics (Chmelař et al., 2026).

3. Immunomodulation: HBOT may reduce inflammation (Wolde et al., 2021) and has been shown to modulate cytokine levels in patients with NSTI (Hedetoft et al., 2021b). 

4. Reduced oedema and improved microcirculation: HBOT may reduce local oedema through vasoconstriction while maintaining oxygen delivery, limiting secondary tissue injury and facilitating antibiotic penetration during severe infections (Hedetoft et al., 2021a).

5. Improved wound healing: By enhancing angiogenesis, fibroblast activity, and collagen deposition, HBOT contributes to wound bed optimisation, which is critical in extensive soft-tissue infections following debridement (André‐Lévigne et al., 2016).

Clinical Evidence Supporting HBOT for Serious Bacterial Infections

The efficacy of adjunctive HBOT for SBIs is supported by decades of clinical experience, case series, and observational studies, particularly for clostridial gas gangrene and NSTIs. However, the treatment protocols described in the clinical literature are heterogeneous, and high-quality randomised controlled trials (RCTs) are scarce. Despite the limited evidence, HBOT is approved by the FDA for gas gangrene and severe infections of the bone and skin (FDA, 2025) and by the Undersea and Hyperbaric Medical Society (UHMS) for NSTIs and chronic refractory osteomyelitis (Mathieu et al., 2017).

1. Necrotising soft-tissue infections: The largest and most consistent body of data concerns NSTIs. Adjunctive HBOT is recommended by some clinical guidelines (James, 2023), particularly when anaerobic organisms are involved or extensive tissue involvement is present. Typically, the treatment protocol for NSTIs includes initiating HBOT at 2.0 to 2.5 ATA for 90 minutes 2–3 times a day for the first few days, followed by 1–2 sessions per day until there is no further extension of necrosis and infection is controlled (Huang, 2024; Shishido et al., 2025). Early observational studies, such as Riseman et al. (1990), found a mortality rate of 23% in patients with necrotising fasciitis treated with an average of 7.4 sessions of adjunctive HBOT for 90 minutes compared with 66% in those receiving surgery and antibiotics alone. More recent cohort studies have also reported lower mortality and reduced surgical debridement (Devaney et al., 2015; Toppen et al., 2024; Shishido et al., 2025). Systematic reviews and meta-analyses of predominantly observational studies report that HBOT, used adjunctively with surgery and antibiotics, is associated with reduced mortality and lower rates of major amputation compared with non-HBOT cohorts in pooled analyses (Huang et al., 2023; Hedetoft et al., 2021a). However, these analyses are limited by selection bias, variable treatment protocols, heterogeneity of patient populations and confounding by indication. 

2. Clostridial myonecrosis (gas gangrene): Historical (Smart et al., 1965; Johnson et al., 1969) and contemporary (Raju et al., 2017) series and cases suggest a mortality benefit when HBOT is added to prompt debridement and antibiotics. Most data are observational; nevertheless, HBOT is recommended for confirmed or suspected clostridial infection (FDA, 2025). The recommended treatment protocol is oxygen at 3 ATA for 90 minutes three times in the first 24 hours and twice a day for the next 2–5 days (Sison-Martinez et al., 2023). Treatment length should be tailored to the patient’s therapeutic response. Surgical debridement should be performed between HBO treatments. Proper antibiotic therapy is also essential.

3. Fournier’s gangrene: In a systematic review of 13 studies with a total of 376 patients with Fournier's gangrene (Schneidewind et al., 2021), the mortality rate of the HBOT-treated group (16.6%) was lower than that in the non-HBOT group (25.9%). In another systematic review and meta-analysis of HBOT for Fournier's gangrene that included 10 retrospective studies, patients who received HBOT had a lower rate of mortality compared to patients who received conventional therapy (Raizandha et al., 2022). However, the mean length of hospital stay and the number of debridement procedures were not significantly different between groups. In these reviews, the HBOT treatments reported were highly heterogeneous but typically involved 5–24 sessions of treatment with 100% oxygen at 2–3 ATA for 90–120 minutes.

4. Osteomyelitis: No RCTs examining the effects of HBOT on refractory osteomyelitis exist, and the reported clinical trials are limited (Hart, 2021). However, in a systematic review (Savvidou et al., 2018) of 45 studies, adjuvant HBOT was effective in 80% of the cohort studies and 95% of the case studies. 

5. Quality of evidence and ongoing research. Systematic reviews emphasise a lack of RCTs for acute NSTIs and other infections and identify the evidence base as low to moderate quality because of confounding and study design limitations (Bennett et al., 2018). A prospective clinical trial (ClinicalTrials.gov NCT07170020) was registered in 2025 to evaluate HBOT versus standard care for necrotising fasciitis/NSTI, reflecting ongoing attempts to generate more rigorous evidence. 

Conclusion

Serious bacterial infections, including NSTIs, clostridial gas gangrene, and refractory osteomyelitis, remain associated with high morbidity and mortality despite advances in surgery and antimicrobial therapy. Adjunctive HBOT enhances oxygen delivery to infected and hypoxic tissues, inhibits anaerobic bacterial growth, improves immune function, and promotes wound healing.

Although most evidence for HBOT in these infections comes from observational studies and case series rather than large RCTs, findings over several decades suggest improved survival, decreased extent of surgical debridement, and improved functional outcomes in appropriately selected patients.

HBOT is generally safe, and when applied early as part of a multidisciplinary approach, it represents a valuable adjunctive therapy for life-threatening bacterial infections, particularly those involving anaerobic or mixed flora.

References

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Elizabeth Gaffney https://www.sourceprojects.co
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