RIFAMPICIN DOES NOT REDUCE MOXIFLOXACIN TISSUE CONCENTRATIONS FOLLOWING ONE-STAGE REVISION IN A PORCINE MODEL OF IMPLANT-ASSOCIATED OSTEOMYELITIS

Aim

This study investigated if co-administration of rifampicin with moxifloxacin led to a decrease in moxifloxacin concentrations in relevant tissues in a porcine model of implant-associated osteomyelitis caused S. aureus. Pharmacokinetics were measured using microdialysis and treatment effect was measured by quantifying bacterial load from implant and periprosthetic bone following a 1-stage revision and antibiotics.

Method

15 female pigs received a stainless-steel implant in the right proximal tibia and were randomized into two groups. Infection was introduced by inoculating the implant with Staphylococcus aureus as previously described¹. On day 7 post surgery, all pigs were revised with implant removal, debridement of implant cavity and insertion of a sterile implant. 7 days of treatment was then initiated with either moxifloxacin 400 mg iv q.d. (M) or moxifloxacin and rifampicin 450 mg iv b.i.d. (RM). At day 14, animals were sedated and microdialysis was applied for continuous sampling of moxifloxacin concentrations during 8 h in five compartments: the implant cavity, cancellous bone in both the infected and non-infected proximal tibia, and adjacent subcutaneous tissue on both the infected and non-infected side using a previously described setup². Venous blood samples were collected. Implant and adjacent bone were removed for analysis.

Results

Comparable cure rates (sterilization of both implant and bone) were observed with 5/8 pigs in the RM group compared to 3/7 in the M group, p= 0.62 (Fisher's exact test). Due to the small number of samples with growth, median log CFU/ml was 0 for implant and bones in both groups.

AUC_0-last was significantly smaller in plasma for the RM group, 407; 315 – 499 min µg/mL vs 625; 536 – 724 min µg/mL (mean;95% CI), p= 0.002 (Student's t-test). For the implant cavity, there was a trend toward a lower AUC_0-last 425; 327 – 524 min µg/ml vs 297; 205 – 389 min µg/ml in the RM group compared to M, yet this difference was not statistically different, p = 0.06. For the other compartments for other parameters (C_max and T_max) across all compartments, there was no difference.

Conclusions

While the AUC_0-last was lower in plasma for animals treated with RM, both the concentrations at the site of infection and treatment outcomes were comparable between groups.