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Effects of rifampicin on moxifloxacin concentrations in porcine cervical spine: a randomized microdialysis study
Josefine Slater1,2, Pelle Hanberg1,2,3, Mathias Alrø Fichtner Bendtsen1,2
1Department of Orthopaedic Surgery, Aarhus University Hospital, Palle Juul-Jensens Blvd 99, 8200 Aarhus N, Denmark.
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.
Insights
Rifampicin significantly reduces moxifloxacin concentrations in spinal tissues, impacting treatment effectiveness for pyogenic spondylodiscitis. This study highlights potential drug interaction concerns for staphylococcal infections.
Area of Science:
- Pharmacology
- Infectious Diseases
- Surgical Research
Background:
- Pyogenic spondylodiscitis presents treatment challenges due to varied guidelines.
- Moxifloxacin and rifampicin combination is considered for staphylococcal infections.
- Rifampicin's impact on spinal tissue moxifloxacin levels is unknown.
Purpose of the Study:
- To determine rifampicin's effect on moxifloxacin tissue concentrations.
- Investigate concentrations in vertebral bone, intervertebral disc, and adipose tissue.
- Utilize a porcine model with microdialysis.
Main Methods:
- Twenty pigs were divided into two groups: moxifloxacin alone (Group A) and moxifloxacin with rifampicin (Group B).
- Drug administration occurred preoperatively over 3-7 days.
- Microdialysis sampled plasma and solid tissues (bone, disc, fat) over 24 hours.
Main Results:
- Coadministration of moxifloxacin and rifampicin reduced free moxifloxacin concentrations in spinal tissues.
- Maximum concentration (Cmax) and area under the curve (AUC0-24) decreased by 66%-79% and 65%-76% respectively in all tissue compartments.
Conclusions:
- Microdialysis confirmed a significant reduction in moxifloxacin Cmax and AUC0-24 in spinal tissues when combined with rifampicin.
- This interaction may affect the efficacy of combined therapy for spinal infections.

