RESUMEN
Animal models of post-traumatic acute osteomyelitis (OM) that closely mimic human scenarios, including infection prophylactic procedures such as debridement and lavage, may provide a better understanding of OM. We contaminated mechanically traumatized rat tibiae (n = 69) with various doses of a Staphylococcus aureus strain (SMH) known to cause human OM and then performed curettage and lavage. Tibiae were harvested 24 h after lavage for assessment of bacterial load and determination of minimal infective doses for 50% (ID50) and 95% (ID95) of rats. Some experiments varied tibial harvest time after lavage (n = 10); for progressive infection, tibiae were evaluated at 7 and 15 days after contamination (n = 17 for each time point). At 24 h after contamination, the ID50 was 1.8 x 10(3) CFU, and the ID95 was 9.2 x 10(3) CFU. Tibial bacterial loads did not increase with inocula greater than the ID95. Lavage removed many bacteria from bone, but it did not prevent subsequent infection or disease. At 15 days after contamination, most tibiae (14 of 17) were infected, with macroscopic and radiological signs of established OM. This newly described rat OM model, with a low ID95 despite prophylactic curettage and lavage, closely mimics events in contaminated human bone injuries. This situation will allow study of early factors in contaminated bone injuries, including clinical interventions that may reduce infection and prevent disease.
Asunto(s)
Fracturas Abiertas/complicaciones , Osteomielitis/microbiología , Infecciones Estafilocócicas/complicaciones , Staphylococcus aureus/patogenicidad , Fracturas de la Tibia/complicaciones , Infección de Heridas/microbiología , Animales , Desbridamiento/métodos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta Inmunológica , Curación de Fractura/inmunología , Fracturas Abiertas/microbiología , Fracturas Abiertas/patología , Masculino , Microscopía Electrónica de Rastreo , Osteomielitis/inmunología , Osteomielitis/patología , Ratas , Ratas Sprague-Dawley , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/patología , Staphylococcus aureus/fisiología , Irrigación Terapéutica/métodos , Tibia/microbiología , Tibia/ultraestructura , Fracturas de la Tibia/microbiología , Fracturas de la Tibia/patología , Infección de Heridas/inmunología , Infección de Heridas/prevención & controlRESUMEN
Bisphosphonates conjugated to fluoroquinolone antibacterials through an intermediate carbon had better activity than conjugates lacking the carbon. Virtually all molar-based activity of these esterified bisphosphonate derivatives was identical to that of its parent. De-esterified free-acid forms retained good activity against most Gram-negative bacteria, but not against Gram-positives. A free-acid derivative remained bound to washed bone and completely inhibited Staphylococcus aureus growth. The more potent parent, ciprofloxacin, failed to bind significantly, and bacterial growth occurred.