Czaplewski Lloyd G, Zeitlinger Marcus, Standing Joseph F
Persica Pharmaceuticals Ltd, 7 Denne Hill Business Centre, Womenswold, Canterbury, Kent, CT4 6HD, UK.
Medical University of Vienna, Department of Clinical Pharmacology, Clinical Pharmacokinetics / Pharmacogenetics and Imaging, Waehringer Guertel 18-20, 1090, Vienna, Austria.
NPJ Antimicrob Resist. 2023 May 10;1(1):1. doi: 10.1038/s44259-023-00002-7.
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.
口服阿莫西林克拉维酸钾和阿莫西林，采用长达100天的延长剂量方案，已显示出对与椎体骨水肿相关的慢性下腰痛（CLBP）（即莫迪克1型改变）的治疗有益，这种骨水肿可能由细菌感染引起，但临床改善程度各不相同。本综述的目的是利用文献中的稀疏数据来估计阿莫西林在椎间盘内的暴露量，并确定是否达到了足够的抗菌暴露水平。椎间盘突出组织中阿莫西林的暴露量约为血清浓度的6.5%。每12小时口服一次阿莫西林，剂量高达1000毫克，不太可能在椎间盘组织中产生有效暴露。每8小时口服500毫克或750毫克阿莫西林的平均暴露量可能达到约50%痤疮丙酸杆菌菌株的疗效目标，但达不到90%痤疮丙酸杆菌菌株的疗效目标。每8小时口服1000毫克阿莫西林的平均暴露量可能达到90%菌株的目标暴露水平。口服阿莫西林治疗CLBP的研究可能剂量都不足。超过1400例患有CLBP和莫迪克1型改变的患者接受了长达100天的口服阿莫西林治疗，但未对全身或椎间盘内的药代动力学进行明显评估。有必要对阿莫西林和其他抗生素、它们的给药方案以及椎间盘内药代动力学进行额外的临床评估，以优化该适应症的治疗。抗菌药代动力学和药效学方面的专业知识应纳入未来研究的设计和实施中。
