Abstract
Aim
Pyogenic spondylodiscitis remains a therapeutic challenge, as demonstrated by divergent treatment guidelines. The combination of moxifloxacin and rifampicin may be an attractive treatment option for cases caused by staphylococci; however, previous studies have reported a reduction in plasma concentrations of moxifloxacin when co-administered with rifampicin. The magnitude of this reduction in spinal tissues is not known. We aimed to investigate the interaction of rifampicin on moxifloxacin tissue concentrations in vertebral cancellous bone, intervertebral disc and subcutaneous adipose tissue in steady-state conditions using microdialysis in a porcine model.
Method
Twenty female pigs were randomized into two groups of ten pigs: Group A received moxifloxacin 400 mg orally once daily for three days preoperatively. Group B received moxifloxacin 400 mg orally for three days preoperatively combined with rifampicin 450 mg twice daily for seven days preoperatively. Measurements were obtained from plasma, vertebral cancellous bone, intervertebral disc and subcutaneous adipose tissue for 24 h. Microdialysis was applied for sampling in solid tissues.
Results
Co-administration of moxifloxacin and rifampicin demonstrated a reduction of free moxifloxacin concentrations in spinal tissues. The peak drug concentration (Cmax) and the area under the concentration-time curve (AUC0–24) in all tissue compartments decreased in the range of 66–79% and 65–76%, respectively.
Conclusions
Using microdialysis, we demonstrated a significant reduction of moxifloxacin Cmax and AUC0–24 in the spinal tissues when co-administered with rifampicin. Further studies are warranted to understand the clinical implications of this finding for the treatment of pyogenic spondylodiscitis.
