A surgical procedure allowed the placement of a silicone rubber catheter in the marrow cavity of the tibia of a rabbit and also allowed the introduction of a sclerosing agent (sodium morrhuate) and cells of Staphylococcus aureus. Osteomyelitis developed in 60% of the animals so treated, and the infecting microorganism was recovered from the infected tibias of the animals that developed this disease. All blood cultures taken 24 h after the infection were negative for S. aureus. Radiological findings consisted of osteolytic changes, the occurrence of sequestration and periosteal reactions, and sclerosis in the infected bones. Sections of bone prepared for histological examination confirmed the diagnosis of osteomyelitis. Transmission and scanning electron microscopy of samples of bone marrow, bone chips, and the catheters taken from the infected tibiae revealed gram-positive cocci embedded in a very extensive matrix of ruthenium red-staining glycocalyx adhering to the bone and the implanted catheter. It is proposed that this extensive glycocalyx served a protective function for the bacteria and was important in bacterial adherence and thus played an important role in bacterial persistence and the development of osteomyelitis in these rabbits.

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Background and Purpose. Pharmacokinetic assessment of drug tissue permeation following iontophoresis is limited. The depth of ketoprofen tissue permeation following cathodic iontophoresis (4 mA, 40 minutes) and the stereoselectivity of drug delivery were examined in this study.Subjects. Ketoprofen (750 mg) was iontophoresed onto one porcine medial thigh, with passive drug permeation conducted on the other thigh.Methods. Skin, subcutaneous fascia, and muscle biopsies from the drug delivery sites were harvested and stored separately, and the “R” and “S” ketoprofen enantiomers were determined.Results. Iontophoretic and passive applications yielded equivalent total ketoprofen concentrations in the skin and fascia. In contrast, multivariate analysis demonstrated that the ketoprofen concentration in the first centimeter of muscle following iontophoresis was greater than the drug concentration in the deeper underlying muscle layers and greater than that delivered to any muscle layer following passive delivery. No transcutaneous stereoselective delivery of ketoprofen was detected.Conclusion and Discussion. Compared with passive delivery, iontophoresis enhances nonstereoselective ketoprofen permeation into the fascia-muscle interface. With delivery to deeper tissue sites, however, there is no apparent enhancement over passive application.