There are particularly difficult infections that resist treatment by sulfa drugs (introduced in the1930s) and penicillin (introduced in the 1940s).

Actinomycosis is a bacterial infection characterized by chronic inflammation and toxic pocket formation. Diagnosis is difficult because the cause is bacteriological and not fungal, a fact only coming to light.  Also, special anaerobic techniques are needed to culture the causative micro-organisms.

Most often actinomycotic lesions involve the face and neck (63%), the thorax (15%) and ileocecal regions (22%).  Pelvic actinomycosis has become more frequently reported with the use of intrauterine devices. Still, the most common form, cervicofacial actinomycosis, typically begins after dental extraction or trauma to the mouth.  Frequently located at the angle of the jaw, the mass begins to drain from multiple extraoral sinuses. The predisposing conditions include poor oral hygiene, dental caries, and oral trauma.

Pulmonary actinomycosis (pneumonia) is usually a result of aspiration. In the ileocecal region, actinomycosis of the gastrointestinal tract is the most common site.  The disease can also manifest in other areas of the GI tract.  Patients with this condition often show a history of appendicitis.  Actinomycotic infection of the bone is usually a result of an adjacent soft tissue infection (75 %) but may also be due to trauma, for instance, to the mandible (jaw bone) or due to blood infection.

The mechanism of action here is the increase in oxygen tension levels which lead to the increased concentration of superoxide dismutase.  Increased levels of this chemical lead to the production of hydrogen peroxide and other oxygen-derived free radicals that are toxic to anaerobic organisms.  Actinomycosis organisms are extremely sensitive to these toxic oxygen radicals.  Most anaerobes lack the enzyme for degrading superoxide dismutase and the hydrogen peroxide-degrading enzyme. During HBOT the increase in oxygen tension leads to elevation of superoxide dismutase.  This occurs in both the intracellular and extracellular spaces.

Favorable clinical results have been reported with adjunctive HBOT in refractory actinomycosis, and it is used with other accepted antimicrobial treatment and surgery.