Intradiscal pharmacokinetics of oral antibiotics to treat Chronic Lower Back Pain.

Oral coamoxiclav and amoxicillin, for extended dose regimens of up to 100 days, have shown benefit in the treatment of Chronic Lower Back Pain (CLBP) associated with vertebral bone oedema, known as Modic type 1 changes, which may be caused by a bacterial infection, but the magnitude of clinical improvement has been variable. The objectives of this review were to use sparse data from the literature to estimate the exposure of amoxicillin in the intervertebral disc, and to determine whether adequate antimicrobial exposure may have been achieved. Exposure to amoxicillin in herniated disc tissue was approximately 6.5% of the serum concentration. Dosing of oral amoxicillin, Q12h, at doses of up to 1,000 mg is unlikely to lead to effective exposure in disc tissue. Mean exposure to 500 mg or 750 mg of oral Q8h amoxicillin may reach the efficacy target for ~50% of Cutibacterium acnes strains, but not for 90% of C. acnes strains. Mean exposure to 1,000 mg of oral amoxicillin Q8h may reach the target exposure for 90% of strains. Oral amoxicillin CLBP studies may all be underdosed. More than 1400 patients with CLBP and Modic type 1 changes have been exposed to oral amoxicillin for up to 100 days, with no apparent evaluation of systemic or intradiscal pharmacokinetics. Additional clinical evaluations of amoxicillin and alternative antibiotics, their dose regimens, and intradiscal pharmacokinetics are warranted to optimize treatment for this indication. Expertise in antibacterial pharmacokinetics and pharmacodynamics should be included in the design and execution of future studies.