Critical analysis of experimental models of periprosthetic joint infection

Because the extreme diversity of clinical situations makes formal clinical trials difficult to carry out, animal models of periprosthetic infection in orthopaedics are needed to understand the aetiology and pathology of these infections, and to test new treatment methods. These experimental models must reproduce the features of the infections encountered in clinical practice. One of the model variables is the method of inoculation: local (intra-articular), intravenous or intra-arterial. Another is the timing of the inoculation: intra-operative or postoperative. Together, these options simulate the different contamination methods: direct, by proximity or blood-borne. However, the chosen inoculation route can also affect the infection rate and severity in the various models, and in some cases do not accurately reproduce the postoperative infections encountered clinically.

The direct inoculation method is the most effective for inducing a local infection on a foreign body in a joint, and the least iatrogenic.

A critical analysis of published studies was carried out to evaluate each model against three endpoints, according to the type of inoculation. The primary endpoint was the infection rate, which should be as close as possible to 100%. The secondary endpoints were the mortality rate and rate of spontaneous healing, both of which should be as low as possible. Twenty-one articles were reviewed.

Intra-articular and intra-medullary inoculations had induction rates between 70 and 100%; intra-arterial inoculations had an induction rate of 100%, while intravenous inoculation had a rate of 47 to 77%. The mortality rates were lower with the intra-articular and intramedullary inoculations (5 to 23%) than for the intra-arterial inoculations (37%) and intravenous inoculations (28 to 56%). The spontaneous healing rate was 0 to 30% for intra-articular and intramedullary inoculations, 30 to 53% for intravenous inoculations and 0% for intra-arterial inoculations.

Direct inoculation methods are most effective at reproducing chronic periprosthetic joints infections, without putting the animal's life at risk or allowing for spontaneous healing. The simulation of blood-borne infections is more random.