A Mechanism for the Amelioration by Hyperbaric Oxygen of Experimental Staphylococcal Osteomyelitis in Rabbits

Abstract

Although hyperbaric oxygen (HBO) is as effective as cephalothin against osteomyelitis due to Staphylococcus aureus in the rabbit, the effect is not by directing killing. To investigate the mechanism, argon washouts (perfusion) and oxygen tensions were measured by intramedullary probes placed in the metaphyses of infected and uninfected tibias. In vitro phagocytic killing activity for S. aureus was determined at oxygen tensions found in these bones under ambient and HBO conditions. Mean tibial oxygen tensions (mm Hg) under ambient conditions were 21 (infected) and 45 (uninfected); under HBO conditions, 104 (infected) and 321 (uninfected). Perfusion was decreased in osteomyelitic bone and was not acutely increased by HBO in either normal or infected bone. Phagocytic killing of S. aureus was markedly decreased at 23 mm Hg of O2, significantly improved at 45 and 109 mm Hg, and most effective at 150 mm Hg. Thus, in osteomyelitic bone, HBO increased intramedullary oxygen to tensions consistent with normal phagocytic function.

Comparative evaluation of daptomycin (LY146032) and vancomycin in the treatment of experimental methicillin-resistant Staphylococcus aureus osteomyelitis in rabbits

“…Although vancomycin is the drug of choice for the treatment of MRSA infections, the results of treatment of experimental methicillin-susceptible S. aureus osteomyelitis have been disappointing (15). Norden and Shaffer (15) have shown that vancomycin kills poorly under anaerobic conditions and postulated that the low oxygen tensions found in osteomyelitic bone (12) decreased the effectiveness of vancomycin in experimental methicillin-susceptible S. aureus osteomyelitis. Although it is difficult to extrapolate data from methicillin-susceptible S. aureus to MRSA osteomyelitis, it is clear that new effective antibiotics are needed to treat MRSA osteomyelitis.…”

“…At least three infected but untreated controls (group 1) were included in each treatment series. Group 2 received daptomycin (4 mg/kg) every 12 h, and group 3 received vancomycin (Lilly) (40 mg/kg) every 6 h. The antibacterial agents were given from day 14 through day 42 (28 days total). Injections were administered subcutaneously into the back of the neck.…”

Nitric-oxide Synthase-2 Linkage to Focal Adhesion Kinase in Neutrophils Influences Enzyme Activity and β2 Integrin Function

“…Previous studies have shown that although the function of ␤ 2 integrins is temporarily inhibited (in humans the effect resolves within 24 h (3)) neutrophil antibacterial responses remain intact (20,21). HBO 2 does not reduce neutrophil viability or cause immunocompromise, as functions such as degranulation and oxidative burst in response to chemoattractants are intact (2,3).…”

Correction of Hypoxia, a Critical Element for Wound Bed Preparation Guidelines: TIMEO2 Principle of Wound Bed Preparation

“…To carry out their specific inflammatory or repair functions, neutrophils, fibroblasts, macrophages, and osteoclasts are all dependent on an environment in which oxygen is not deficient. Improved leukocyte function of bacterial killing 11,50,51 and synergistic effects with antibiotics 12,13 have been demonstrated. Supression of synthesis of many bacterial toxins 12 occurs when tissue PO 2 values are sufficiently elevated during treatment.…”