Post Hunter K, Blankespoor Michael G, Ierulli Victoria K, Morey Tucker D, Schroeppel J Paul, Mulcahey Mary K, Vopat Bryan G, Vopat Matthew L
Department of Orthopedic Surgery and Sports Medicine, University of Kansas School of Medicine, Kansas City, KS.
Department of Orthopaedic Surgery, Tulane University School of Medicine, New Orleans, LA.
Kans J Med. 2023 Oct 30;16(3):272-276. doi: 10.17161/kjm.vol16.20357. eCollection 2023.
Intra-articular antibiotics have been proposed as a treatment for septic arthritis to allow for high local concentrations without subjecting a patient to the toxicity/side effects of systemic therapy. However, there is concern for chondrotoxicity with intra-articular use of these solutions in high concentrations. The purpose of this systematic review was to evaluate the intra-articular use of antibiotics and antiseptic solutions, and to determine their association with chondrolysis following or administration.
A systematic review was conducted following PRISMA guidelines through PubMed, Clinical Key, OVID, and Google Scholar. Studies in English were included if they evaluated for chondrotoxicity following antibiotic exposure.
The initial search resulted in 228 studies, with 36 studies meeting criteria. These 36 studies included manuscripts that studied 24 different agents. Overall, 7 of the 24 (29%) agents were non-chondrotoxic: minocycline, tetracycline, chloramphenicol, teicoplanin, pefloxacin, linezolid, polymyxin-bacitracin. Eight (33%) agents had inconsistent results: doxycycline, ceftriaxone, gentamicin, vancomycin, ciprofloxacin, ofloxacin, chlorhexidine, and povidone iodine. Chondrotoxicity was evident with 9 (38%) agents, all of which were also dose-dependent chondrotoxic based on reported estimated half maximal inhibitory concentrations (est. IC50): amikacin (est. IC50 = 0.31-2.74 mg/mL), neomycin (0.82), cefazolin (1.67-3.95), ceftazidime (3.16-3.59), ampicillin-sulbactam (8.64 - >25), penicillin (11.61), amoxicillin (14.01), imipenem (>25), and tobramycin (>25). Additionally, chondroprotective effects of doxycycline and minocycline were reported.
This systematic review identified agents that may be used in the treatment of septic arthritis. Nine agents should be avoided due to their dose-dependent chondrotoxic effects. Further studies are needed to clarify the safety of these medications for human intra-articular use.
关节腔内使用抗生素已被提议作为治疗化脓性关节炎的一种方法，以便在不使患者遭受全身治疗毒性/副作用的情况下实现高局部浓度。然而，人们担心高浓度关节腔内使用这些溶液会产生软骨毒性。本系统评价的目的是评估抗生素和防腐溶液的关节腔内使用情况，并确定其与给药后软骨溶解的关联。
按照PRISMA指南，通过PubMed、Clinical Key、OVID和谷歌学术进行系统评价。纳入的英文研究需评估抗生素暴露后的软骨毒性。
初步检索得到228项研究，其中36项符合标准。这36项研究包括研究24种不同药物的手稿。总体而言，24种药物中有7种（29%）无软骨毒性：米诺环素、四环素、氯霉素、替考拉宁、培氟沙星、利奈唑胺、多粘菌素-杆菌肽。8种（33%）药物结果不一致：强力霉素、头孢曲松、庆大霉素、万古霉素、环丙沙星、氧氟沙星、氯己定和聚维酮碘。9种（38%）药物存在明显的软骨毒性，根据报道的估计半数最大抑制浓度（估计IC50），所有这些药物也具有剂量依赖性软骨毒性：阿米卡星（估计IC50 = 0.31 - 2.74 mg/mL）、新霉素（0.82）、头孢唑林（1.67 - 3.95）、头孢他啶（3.16 - 3.59）、氨苄西林-舒巴坦（8.64 ->25）、青霉素（11.61）、阿莫西林（14.01）、亚胺培南（>25）和妥布霉素（>25）。此外，还报道了强力霉素和米诺环素的软骨保护作用。
本系统评价确定了可用于治疗化脓性关节炎的药物。9种药物因其剂量依赖性软骨毒性作用应避免使用。需要进一步研究以阐明这些药物在人体关节腔内使用的安全性。
