Characterization of a chronic infection in an internally‐stabilized segmental defect in the rat femur

Abstract

The aim of this study was to characterize a new model of chronic osteomyelitis with clinically relevant features. A segmental defect of critical size was surgically created in the rat femur, stabilized with a polyacetyl plate and Kirschner wires, and contaminated with bacteria. The animals were allowed to recover while the contamination progressed to a chronic infection. At a later point in time, the defect was surgically debrided without removing the implant. Further treatments of interest, such as antibiotic therapy or application of an osteogenic agent, could be introduced at this time. To implement this model, an initial experiment was performed to determine the bacterial inoculum and time from contamination that would reliably result in an infected defect without causing excessive bone damage by the time debridement surgery was performed. The number of recovered bacteria, degree of radiographic bony lysis, and torsional stiffness of the defect fixation were measured in 192 rats as a function of 4 inocula of Staphylococcus aureus (lo', lo4, 10' or lo6 CFUs) and 4 times from contamination (1,2, 3 or 4 weeks). A lo4 CFU inoculum over 2 weeks was found to consistently create an infection without severe lysis and loss of fixation stability. Based on these values, a second experiment was performed in 96 rats to characterize the debrided defect over time (2,4,8 and 12 weeks after debridement), with and without 4 weeks of the antibiotic ceftriaxone, in terms of the same outcome variables. Infection was persistent in all animals in spite of debridement and antibiotic therapy. Antibiotic therapy did not reduce the degree of bony lysis. Compared with animals not given antibiotic, bacterial counts significantly decreased during the period of antibiotic therapy, but then rebounded to significantly higher levels at 12 weeks. This model allows us to perform further studies on differing regimens of antibiotic therapy and their relationship to surgical dtbridement, and on the efficacy of osteogenic agents in the presence of infection.

Can Normal Fracture Healing Be Achieved When the Implant Is Retained on the Basis of Infection? An Experimental Animal Model

“…Torque to failure and stiffness both were lower in the infection group than in the control group at 6 weeks, but with the numbers available for testing, they were not different at 3 weeks (p = 0.615 and p = 1, respectively; Table 2 [3][4][5][6][7][8][9][10][11][12][13][14][15][16]; p = 0.004) both were greater in the control group than in the group with infection. Maximum torque to failure was lower in the infection group than in the control group at all time points.…”

“…2 The infection group at 6 weeks shows callus tissue, consisting predominantly of reactive trabecular bone and focally of cartilage (Stain, hematoxylin-eosin; original magnification, 9100). practice, antibiotics are given according to the bacteria isolated from the infection side [3]. It is possible that the differences between the groups would have been less dramatic had we given antibiotics; however, to ensure infection in the infection group in this model, antibiotics were not used.…”

“…In previous studies of infected fracture models, callus tissue was observed in the infected fracture area under the supply of antibiotics [2,3,24]. The difference from these studies is that no antibiotics were used and no segmental defects were created.…”

“…Radiographic analysis at 6 weeks demonstrated the fracture line was less distinct (Lane and Sandhu score of 2-3) in the infection group and complete union was observed (Lane and Sandhu score of [3][4] in the control group (p = 0.001). Semiquantitative histology scores were not different between the noninfected controls and the rats with infection (score 10 versus 9).…”

“…Results Infection decreased callus strength at 6 weeks. Torque to failure (299.07 ± 65.53 Nmm versus 107.20 ± 88.81, mean difference with 95% confidence interval, 192 ; p = 0.007) and stiffness at 6 weeks (11.28 ± 2.67 Nmm versus 2.03 ± 1.68, mean difference with 95% confidence interval, 9 [3][4][5][6][7][8][9][10][11][12][13][14][15][16]; p = 0.004) both were greater in the control group than in the group with infection.…”