Robbie P Miller1, Marie E Berlouis1, Alan G Hall1, A Hamish R W Simpson2, Innes D M Smith3, Andrew C Hall1. 1. Centre for Integrative Physiology, Deanery of Biomedical Sciences, University of Edinburgh, Edinburgh, Scotland, UK. 2. Musculoskeletal Research Unit, Department of Orthopaedic Surgery, University of Edinburgh, Edinburgh, Scotland, UK. 3. Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, Scotland, UK.
Abstract
OBJECTIVE: Septic arthritis results from joint infection by Staphylococcus aureus, which produces potent α-toxin causing cell death, potentially leading to permanent cartilage damage. Treatment is by joint irrigation and antibiotics, although it is unclear if, following treatment with antibiotics which cause bacterial lysis, there is release of additional stored α-toxin. DESIGN: A rabbit erythrocyte hemolysis assay was optimised to assess biologically-active α-toxin from cultured S. aureus α-toxin strain DU5946. Hemoglobin release was measured spectrophotometrically following addition of a bacteriostatic antibiotic (linezolid) or a bacteriolytic antibiotic (penicillin). A bovine cartilage model of septic arthritis was used to test the protective effects of antibiotics against S. aureus infection. RESULTS: During S. aureus culture, α-toxin levels increased rapidly but the rate of rise was quickly (within 20 minutes) suppressed by linezolid (25 μg/mL). Penicillin also reduced the increase in α-toxin levels; however, the time course was relatively slow compared to linezolid even at high concentrations (50,000 U/mL). The efficacy of penicillin (250,000 U/mL) at reducing the rise in α-toxin was approximately 8% less than that of linezolid (P < 0.05) suggesting the presence of additional toxin. This could be due to a delayed action of penicillin, and/or release of a small pool of stored α-toxin from dying bacteria. In a bovine cartilage model, however, there was no difference between the protection of in situ chondrocytes against S. aureus by penicillin or linezolid (P > 0.05). CONCLUSION: The results suggested that equally effective protection of chondrocytes against S. aureus septic arthritis may be obtained by the bacteriostatic or bacteriolytic antibiotics tested.
OBJECTIVE: Septic arthritis results from joint infection by Staphylococcus aureus, which produces potent α-toxin causing cell death, potentially leading to permanent cartilage damage. Treatment is by joint irrigation and antibiotics, although it is unclear if, following treatment with antibiotics which cause bacterial lysis, there is release of additional stored α-toxin. DESIGN: A rabbit erythrocyte hemolysis assay was optimised to assess biologically-active α-toxin from cultured S. aureus α-toxin strain DU5946. Hemoglobin release was measured spectrophotometrically following addition of a bacteriostatic antibiotic (linezolid) or a bacteriolytic antibiotic (penicillin). A bovine cartilage model of septic arthritis was used to test the protective effects of antibiotics against S. aureus infection. RESULTS: During S. aureus culture, α-toxin levels increased rapidly but the rate of rise was quickly (within 20 minutes) suppressed by linezolid (25 μg/mL). Penicillin also reduced the increase in α-toxin levels; however, the time course was relatively slow compared to linezolid even at high concentrations (50,000 U/mL). The efficacy of penicillin (250,000 U/mL) at reducing the rise in α-toxin was approximately 8% less than that of linezolid (P < 0.05) suggesting the presence of additional toxin. This could be due to a delayed action of penicillin, and/or release of a small pool of stored α-toxin from dying bacteria. In a bovine cartilage model, however, there was no difference between the protection of in situ chondrocytes against S. aureus by penicillin or linezolid (P > 0.05). CONCLUSION: The results suggested that equally effective protection of chondrocytes against S. aureus septic arthritis may be obtained by the bacteriostatic or bacteriolytic antibiotics tested.
Authors: C J Mathews; G Kingsley; M Field; A Jones; V C Weston; M Phillips; D Walker; G Coakley Journal: Postgrad Med J Date: 2008-05 Impact factor: 2.401
Authors: I D M Smith; J P Winstanley; K M Milto; C J Doherty; E Czarniak; S G B Amyes; A H R W Simpson; A C Hall Journal: Osteoarthritis Cartilage Date: 2013-07-27 Impact factor: 6.576