Haematogenous models of septic arthritis have some inherent disadvantages, such as the manifestation of arthritis relies on chance, the size of the inoculum is unknown and the number of animals to be studied cannot be reduced because the animals cannot serve as their own controls. This study aimed to develop a rat model of knee septic arthritis by injecting a known inoculum of Staphylococcus aureus into the joint. The left knees of 27 Sprague Dawley rats were injected with four different inoculum concentrations of a sensitive strain of S. aureus (30,000 colony-forming units (CFUs), n = 3; 18,550 CFUs, n = 6; 15,500 CFUs, n = 9; and 7700 CFUs, n = 9); the right knees served as controls. Clinical, microbiological and histological variables were assessed two and seven days later. The main criterion for diagnosing septic arthritis was a positive culture of synovial fluid. The rate of microbiologically confirmed septic arthritis was high for all inoculum concentrations (3/3, 6/6, 8/9 and 7/9, respectively), and the rate of bacteraemia was also high. Animal welfare was better for the two lowest inoculum concentrations. No animal reached the pre-established humane end points. Overall, the third inoculum was considered the most suitable. Thus, acute septic arthritis can be caused in rats by inoculating 15,000 CFUs of an ATCC strain of S. aureus directly into the knee joint. Overall, the model seems to be useful for studying the effectiveness of drugs for the treatment of acute septic arthritis.
ResumenIntentar el tratamiento retentivo de material protésico ante heridas quirúrgicas infectadas por gérmenes resistentes es objeto de debate, especialmente cuando el agente causal es un Staphylococcus aureus resistente a meticilina (SARM). Una paciente diabética y con obesidad tipo I sufrió infección de la herida quirúrgica tras artroplastia de rodilla que no evolucionó bien con antibioterapia empírica y terapia hiperosmolar. Se planificó una reintervención que fue demorada por motivos extramédicos (falta de terapia de presión negativa para cubrir la herida postoperatoria, pues se preveía no poder realizar cierre primario). Mientras se conseguía este material, y tras obtener el consentimiento de la paciente, se iniciaron irrigaciones de la herida con sevoflurano tópico off-label, pues ese fármaco ha mostrado capacidad antimicrobiana. La evolución clínica fue excelente desde el inicio a pesar de que en el cultivo se aisló un SARM resistente a la antibioterapia empírica, por lo que se desestimó la reintervención y se continuó con sevoflurano tópico junto a la antibioterapia dirigida por antibiograma, lográndose la curación completa de la herida tras 6 semanas. Durante ese tiempo, la paciente no experimentó ningún efecto adverso atribuible al sevoflurano. El sevoflurano tópico aparece como una valiosa nueva opción terapéutica ante heridas postoperatorias infectadas, especialmente cuando los gérmenes causantes son resistentes a los antibióticos convencionales.
Objectives We investigated the effects of repeated intra-articular injections of liquid sevoflurane to articular structures, as this inhalational anesthetic is being repurposed as an antimicrobial agent, which would make sevoflurane a novel alternative for the treatment of septic arthritis. Methods The left knees of nine Sprague-Dawley rats were injected with 150 μL of liquid sevoflurane for five consecutive days, whereas the right knees were injected with the same volume of saline to serve as controls. Animals were examined daily for clinical signs of local and systemic toxic effects attributable to sevoflurane. Rats were euthanized in groups of three at days 7, 14, and 35 after the first injection, and left and right knees were sent for histological assessment. Results Local signs on knees consisted of transient bilateral scabs, and an unexpected subcutaneous emphysema affecting only left knees, which was attributed to sevoflurane. No rat presented with limp, and animal welfare was good during the study period. Two out of the three left knees from rats sacrificed at day 7 showed mild histological changes, specifically a mild infiltration of lymphocytes. All other seven left knees as well as all nine right knees were completely normal at histological examination. Conclusion We concluded that repeated intra-articular injections of sevoflurane seemed safe for articular structures in noninfected knees. Further studies focused on the safety of intra-articular sevoflurane in infected knees, as well as on its effectiveness for the treatment of septic arthritis are warranted.
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