Effects of the increase in partial pressure of oxygen on development and viability of bacteria

These effects have been studied on experimental models of bacterial infections both in vitro and in vivo.

2.2.1 In vitro

Pressures of oxygen above 4 mmHg are quickly lethal for strict anaerobes. Pressures of oxygen in the range of normoxia (20 % of O2; PO2 of 152 mmHg) are lethal after a 2-hour exposure for Peptococcus magnus, after 5 hours for Bacteroides fragilis and after 10 hours for Clostridium perfringens9.

HBO has bacteriostatic and even bactericidal effects on Clostridia. The inhibiting or lethal effect of oxygen varies with the strain of Clostridium the bacteria reproduction cycle (development phase) pressures of oxygen exposure duration and culture media. Quiescent spores of Clostridium perfringens are not susceptible to oxygen toxicity. In vitro, HBO has bactericidal effects on Clostridium perfringens C. novyi C. histolyticum and C. tetani, whereas C. bifermentans and C. septicum are more resistant10. Blood or tissue debris impede the effects of oxygen since the catalase they produce destroys the autodestructive peroxides produced in an oxygenated atmosphere by the Clostridia4'110'12.

One of the major benefits of HBO is the inhibiting effect on the development of toxins. This is inhibited at pressures of oxygen above 80 mmHg13,14. In contrast, although HBO stops the activity of certain toxins such as theta-toxins, it has no effect on previously produced alpha-toxins11.

Facultative anaerobes and aerobes survive in hyperoxia (PO2 under 760 mmHg), whereas a 24-hour exposure at 3 ata 100% O2 has a bactericidal effect on Pseudonomas aeruginosa Proteus vulgaris and Salmonella typhi15.

High pressures of oxygen can inhibit or stimulate the development of facultative anaerobes or strict aerobes. Aerobes provide a 2-phase response to an increase in pressure of oxygen. Usually development of aerobic bacteria is stimulated in pressures up to 1.5 ata 100 % O2, and inhibited at higher pressures16'17. A bacteriostatic effect has been observed on E. coli18'19, as well as on many Enterobacteria, Pseudonomas aeruginosa and Enterococcus faecalis16 after exposure to pressures of oxygen between 1.5 and 3 ata. The bacteriostatic effect has been observed for short exposure durations at 8-hour intervals20.

Most of the experimental research on the activity of HBO in infections involves anaerobic infections. As early as 1972 Holland proved the effectiveness of HBO as monotherapy in a randomized study involving a model of Clostridium infection in mice21. Demello, comparing surgical debridement, antibiotics and HBO (100 % O2, 3 ata, 2-hour sessions, 3 times a day on day1, twice on day 2, once on day 3) in a model of experimental gas gangrene in dogs (Clostridium perfringens) obtained the best survival rate by combining the three22. Hill & Osterhout have shown the effectiveness of HBO in two models of infection in mice (implantable disks, injection of Clostridium perfringens)11' Later studies have shown that the effectiveness of HBO increased when the delay between inoculation and the administration of HBO was reduced. HBO has also been found effective for treating intrahepatic micro-abscesses involving Bacteroides fragilis and Fusobacterium necrophorum in mice, the latter with greater effectiveness23.

In 1986 Thom showed the usefulness of HBO in models of peritonitis in rats induced by inoculations combining E. coli, Enterococci, Bacteriodes fragilis or fecal flora24. Using inoculations of E. coli and Bacteriodes fragilis in the same model of peritonitis in rats, Muhvich et al also showed the effectiveness of combining HBO, surgery and antibiotics25. More recently, Stevens26 and Hirn27 confirmed the additional benefit provided by HBO when combined with antibiotics and surgery.

Although there are no controlled studies, the effectiveness of adjunctive HBO on anaerobic soft tissue infections in combination with antibiotic therapy and surgery has been confirmed clinically by a number of research teams over the last 30 years28.

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