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This study evaluated the effects of combining antibiotic therapy with the application of a nonsteroidal anti-inflammatory drug on the degradation of articular cartilage for an animal model of Staphylococcal septic arthritis. Rabbits were infected intra-articularly with Staphylococcus aureus. Antibiotic treatment started 18 hours after infection and continued for 7 days. Treatment with the nonsteroidal anti-inflammatory drug naproxen sodium started 24 hours before infection and continued for either 3 or 7 weeks. The cartilage matrix of uninfected and infected knees was quantified by analysis of glycosaminoglycan and collagen content. Three weeks after infection, the combined treatment of the nonsteroidal anti-inflammatory drug and antibiotics reduced the loss of glycosaminoglycan and collagen from the cartilage of the infected knee by 15 and 30%, respectively, compared with antibiotic treatment alone. Continuing treatment with naproxen sodium for 7 weeks reduced the loss of collagen by 50% when compared with antibiotic treatment alone. The longer period of treatment with naproxen sodium showed little further effect on the loss of glycosaminoglycan than that observed for the 3-week treatment. Treatment with this drug and antibiotics reduced swelling of the knee and levels of prostaglandin E2 in the synovial fluid. The data support the hypothesis that decreasing post-infectious inflammation by adding the drug to a standard antibiotic regimen reduces cartilage damage from Staphylococcal septic arthritis.

A study of 150 corneal donor-recipient grafts, examined for ABO type, revealed that 25% of the grafts were from corneas from incompatible donors. Recipients with histocompatible sensitization exposures such as prior corneal transplant, one or more pregnancies, or one or more blood transfusions were no more likely to experience graft failure if the graft were from an ABO incompatible donor than from a compatible donor. Of 13 graft failures (8%), three of the failed grafts were from AB donors, a significant result. No detrimental effect of transplanting across the ABO barrier could be proven with assurance for any parameter.

A single intravenous dose of one gram of cefazolin was administered prophylactically to forty-eight patients undergoing total joint replacement. The serum half-life of the antibiotic was 1.8 hours, the same value found in normal volunteers. The mean concentration in bone during surgery was 5.7 micrograms per gram of bone. The mean concentration in synovial fluid during surgery was 24.4 micrograms per milliliter of fluid.

An understanding of the absorption of antibiotics from joints was investigated comparing intraarticular (i.a.) absorption with intramuscular (i.m.) absorption in a rabbit knee model. The antibiotics investigated were methicillin, cephalothin, cefazolin, cefoxitin, amikacin, neomycin, kanamycin, and gentamicin. Absorption was measured both in animals in which the knee joint was infected with Staphylococcus aureus and in normal animals. The pattern of absorption was similar among different antibiotics. On an average, antibiotics are absorbed from infected joints 37% slower than from an i.m. injection. In animals that are not infected i.a. antibiotics are actually absorbed 12% faster than i.m. antibiotics. Thus, i.a. antibiotics are absorbed rapidly and similarly to i.m. injection and should be included in total dose calculations for antibiotic regimens, especially with regard to their potential toxicity.

In joints with bacterial arthritis, continuing prolonged destruction of cartilage may occur in spite of prompt, effective antibiotic therapy. We measured the extent to which early antibiotic therapy with ceforanide altered the degradation of the cartilage after arthritis due to Staphylococcus aureus had been produced in the knee joint in rabbits. Degradation of the cartilage was quantified by analyses for glycosaminoglycan and collagen. Three weeks after the infection was produced, the cartilage had lost more than half of its glycosaminoglycan whether the antibiotic therapy had been started at one, two, or seven days after infection. Beginning the antibiotic treatment one day after infection reduced over-all loss of collagen by 37 per cent and decreased the area of erosion of the infected articular surfaces. When antibiotic treatment was begun at four, eight, or twelve hours after infection, the loss of glycosaminoglycan averaged 18 per cent. Prophylaxis with antibiotics completely prevented any degradation of the cartilage. Clinical relevance: The findings reported here show how rapidly cartilage loses glycosaminoglycan when it is involved by arthritis caused by staphylococci and how early treatment of the infection reduces the loss of collagen. There is less protection against loss of glycosaminoglycan. The results emphasize the need for early diagnosis and treatment of infectious synovitis and support the rationale for early administration of antibiotics without waiting for identification of the responsible bacteria.

An animal model was developed to study whether Staphylococcus aureus could penetrate a sutured wound. Six days after bacteria were applied to sutured incisions, viable organisms could be recovered from the depths of the wounds in the majority of cases. Specifically, bacteria could be recovered in 23 of 24 wounds when they were applied 1 day after suturing, in 17 of 24 wounds when they were applied 4 days after suturing, and in 13 of 24 when applied 7 days after suturing. When Steri-strips® were used to close the wounds, bacteria could not be recovered from any of 24 wounds when bacteria were applied 4 or 7 days after wound closure. When bacteria were applied 5 min after sutures had been placed but without incision, bacteria could be recovered in three of 12 cases and in two of 12 cases when they were applied 7 days after suturing. These results demonstrate that bacteria can penetrate sutured wounds. The sutures themselves probably contributed to this phenomenon.

A single intravenous 2 g dose of cefoxitin, a broad spectrum antibiotic, was administered prophylactically just prior to operation on 60 patients undergoing total joint replacement (30 total hip replacements, 30 total knee replacements). Specimens of blood, bone, and synovial fluid were obtained during the operative procedure and assayed for cefoxitin concentration. Peak serum levels drawn five minutes after completion of antibiotic administration showed an average of 191 mcg/ml. Synovial fluid specimens were obtained an average of 33 minutes following antibiotic administration with a mean cefoxitin concentration of 72 mcg/ml. Bone samples from either the femoral condyle or femur head were taken an average of 65 minutes after the antibiotic was given and showed a mean cefoxitin concentration of 12 mcg/g. Simultaneous serum concentration was 63 mcg/ml. No allergic reactions occurred despite a history of skin rash after penicillin in eight patients. One patient developed deep infection caused by poor healing of the skin over the surgical site, thus leading to infection and involvement of the joint well after prophylaxis ended.