Abstract
The increasing clinical incidence and host risk of open fractureโassociated infections, as well as the reduced effectiveness of conventional antibiotics to treat such infections, have driven the development of new therapies for the prophylaxis of open fractureโassociated infections. We investigated percutaneous supplementation of a natural cytokine (i.e., interleukin 12p70 or ILโ12) at an open fracture site to reduce open fractureโassociated infections. We also determined the efficacy of the combination therapy of ILโ12 and conventional antibiotic therapy in the prophylaxis of open fractureโassociated infections. An open femur fracture infection model was produced by direct inoculation of a clinical isolate of Staphylococcus aureus after creating a femur fracture using rats. The animals were assigned to one of four groups: no drug administration, percutaneous supplementation of ILโ12, intraperitoneal administration of the antibiotic ampicillin, or percutaneous ILโ12 in combination with intraperitoneal ampicillin. Animals were euthanized at postoperative days 6, 10, 14, and 21. Percutaneous ILโ12 led to a reduction in infection at postoperative days 6 and 10. For the first time, exogenous ILโ12 was found to have additive effects in the prevention of infection when combined with conventional treatment (i.e., antibiotic therapy). Combination therapy of ampicillin and ILโ12 substantially reduced the infection rate at postoperative day 6 and also decreased the time needed for complete inhibition of infection. Therefore, exogenous ILโ12, providing a mechanism of protection independent of antibiotic resistance, complements the routine use of antibiotics. ยฉ 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:196โ202, 2012