Effects of rifampicin on moxifloxacin concentrations in porcine cervical spine: a randomized microdialysis study.

ABSTRACT

BACKGROUND: 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 coadministered with rifampicin. The magnitude of this reduction in spinal tissues is not known. OBJECTIVES: To investigate the effect of rifampicin on moxifloxacin tissue concentrations in vertebral cancellous bone, the intervertebral disc and subcutaneous adipose tissue under steady-state conditions using microdialysis in a porcine model. METHODS: Twenty female pigs were randomized into two groups of 10 pigs. Group A received 400 mg of moxifloxacin orally once daily for 3 days preoperatively. Group B received 400 mg of moxifloxacin orally once daily for 3 days preoperatively combined with 450 mg of rifampicin twice daily for 7 days preoperatively. Measurements were obtained from plasma, vertebral cancellous bone, the intervertebral disc and subcutaneous adipose tissue for 24 h. Microdialysis was applied for sampling in solid tissues. RESULTS: Coadministration of moxifloxacin and rifampicin demonstrated a reduction of free moxifloxacin concentrations in spinal tissues. Cmax and AUC0-24 in all tissue compartments decreased in the ranges 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 coadministered with rifampicin.