Advances in the Management of Bacterial Septic Arthritis
There is an interesting debate emerging on the use of adjunctive corticosteroids in the treatment of septic arthritis. Two randomized, double-blind, placebo-controlled trials in 2003 and 2011 revealed that concomitant dexamethasone use in the treatment of septic arthritis in children shortened the fever, hospital stay and duration of disease compared with those treated with antibiotics alone. Odio et al. enrolled 123 children with septic arthritis into their study and a 4-day course of dexamethasone 0.2 mg/kg was administered intravenously every 8 h given in combination with antibiotic treatment compared with a second treatment group who received antibiotic therapy alone. Harel et al. included 49 children with septic arthritis and 0.15 mg/kg of dexamethasone intravenously was given for 4 days. Children who received concomitant dexamethasone therapy had a favorable outcome compared with those without dexamethasone therapy. However, there are no equivalent studies conducted in adult patients with bacterial septic arthritis.
In animal models, the use of intraperitoneal bisphosphonates has been shown to be effective in the reduction of bone destruction. This is thought to be due to the effect of bisphosphonates on skeletal osteoclastic activity in experimental S. aureus-induced arthritis. Again, there are no human studies to date.
A recent animal study in 2011 showed that the combination of anti-TNF-α (etanercept) therapy and antibiotic therapy (cloxacillin) has beneficial effects on the outcome of staphylococcal arthritis and sepsis. An arthritogenic dose and a septic dose of S. aureus were inoculated into two groups of mice and the arthritic frequency and arthritic index were measured along with mortality. A reduction in arthritic frequency (68 vs 89%; p = 0.07) and arthritic index (0.9 vs 1.67; p = 0.015) was observed in the mice who had combination treatment compared with the mice given antibiotics alone at day 10 and 14. In the group of animals who received the septic dose of S. aureus, more than 60% of the mice in the combination treatment group survived and recovered completely, while all the mice treated with cloxacillin alone died within a week. The authors commented on the potential danger of the inadequate use of antibiotics when combined with anti-TNF-α therapy since anti-TNF-α therapy has been associated with the development of certain infections, including septic arthritis itself. The recent review by Galloway et al. revealed that there is increased risk of S. aureus septic arthritis in patients with rheumatoid arthritis who are treated with anti-TNF-α therapy and the risk is highest in the early months of treatment. There are also studies that have raised the awareness of the increased risk of sepsis in patients treated with anti-TNF-α therapy.
Two experimental mouse models of staphyloccal and streptococcal septic arthritis have already been presented in this paper. It is worth noting that these studies not only shed light on the pathogenesis of disease but also provide ideas for potential novel targets for adjunctive therapies in the treatment of joint sepsis. Tarkowski's S. aureus model demonstrates a possible beneficial role for cytokines such as IL-1, IL-10, TNF-α and lymphotoxin-α. Tissi's model of group B streptococcal arthritis has shown that both IL-10 and IL-12 can ameliorate both the morbidity and mortality associated with disease. In addition, more recent work from Tissi's group has shown that a lack of B7-1 and B7-2 immunoregulatory molecules can modulate the severity of group B streptococcus sepsis in their mouse model.
These animal studies have suggested that the use of cytokines in both staphylococcal and streptococcal bacterial septic arthritis could enhance the disease outcome in human patients although the work has yet to be translated into human studies.
Future Developments
There is an interesting debate emerging on the use of adjunctive corticosteroids in the treatment of septic arthritis. Two randomized, double-blind, placebo-controlled trials in 2003 and 2011 revealed that concomitant dexamethasone use in the treatment of septic arthritis in children shortened the fever, hospital stay and duration of disease compared with those treated with antibiotics alone. Odio et al. enrolled 123 children with septic arthritis into their study and a 4-day course of dexamethasone 0.2 mg/kg was administered intravenously every 8 h given in combination with antibiotic treatment compared with a second treatment group who received antibiotic therapy alone. Harel et al. included 49 children with septic arthritis and 0.15 mg/kg of dexamethasone intravenously was given for 4 days. Children who received concomitant dexamethasone therapy had a favorable outcome compared with those without dexamethasone therapy. However, there are no equivalent studies conducted in adult patients with bacterial septic arthritis.
In animal models, the use of intraperitoneal bisphosphonates has been shown to be effective in the reduction of bone destruction. This is thought to be due to the effect of bisphosphonates on skeletal osteoclastic activity in experimental S. aureus-induced arthritis. Again, there are no human studies to date.
A recent animal study in 2011 showed that the combination of anti-TNF-α (etanercept) therapy and antibiotic therapy (cloxacillin) has beneficial effects on the outcome of staphylococcal arthritis and sepsis. An arthritogenic dose and a septic dose of S. aureus were inoculated into two groups of mice and the arthritic frequency and arthritic index were measured along with mortality. A reduction in arthritic frequency (68 vs 89%; p = 0.07) and arthritic index (0.9 vs 1.67; p = 0.015) was observed in the mice who had combination treatment compared with the mice given antibiotics alone at day 10 and 14. In the group of animals who received the septic dose of S. aureus, more than 60% of the mice in the combination treatment group survived and recovered completely, while all the mice treated with cloxacillin alone died within a week. The authors commented on the potential danger of the inadequate use of antibiotics when combined with anti-TNF-α therapy since anti-TNF-α therapy has been associated with the development of certain infections, including septic arthritis itself. The recent review by Galloway et al. revealed that there is increased risk of S. aureus septic arthritis in patients with rheumatoid arthritis who are treated with anti-TNF-α therapy and the risk is highest in the early months of treatment. There are also studies that have raised the awareness of the increased risk of sepsis in patients treated with anti-TNF-α therapy.
Two experimental mouse models of staphyloccal and streptococcal septic arthritis have already been presented in this paper. It is worth noting that these studies not only shed light on the pathogenesis of disease but also provide ideas for potential novel targets for adjunctive therapies in the treatment of joint sepsis. Tarkowski's S. aureus model demonstrates a possible beneficial role for cytokines such as IL-1, IL-10, TNF-α and lymphotoxin-α. Tissi's model of group B streptococcal arthritis has shown that both IL-10 and IL-12 can ameliorate both the morbidity and mortality associated with disease. In addition, more recent work from Tissi's group has shown that a lack of B7-1 and B7-2 immunoregulatory molecules can modulate the severity of group B streptococcus sepsis in their mouse model.
These animal studies have suggested that the use of cytokines in both staphylococcal and streptococcal bacterial septic arthritis could enhance the disease outcome in human patients although the work has yet to be translated into human studies.