Systematic Review of Intra-Articular Use of Antibiotics and Antiseptic Irrigation and their Association with Chondrolysis

Abstract

Category: Arthroscopy; Other Introduction/Purpose: Intra-articular antibiotics have been proposed as a treatment for septic arthritis to allow for high local concentrations without subjecting a patient to systemic therapy and its associated toxicity/side effects. However, there is concern for chondrotoxicity with intra-articular use of antimicrobials and antiseptic solutions in high concentrations. The purpose of this systematic review was to evaluate the intra-articular use of antibiotics and antiseptic solutions, determine their association with chondrolysis following in vitro or in vivo administration, and identify the dosages at which they become chondrotoxic. Methods: A systematic review was conducted following the PRISMA guidelines through PubMed, Clinical Key, OVID, and Google Scholar. Studies were included if they were written in the English language and evaluated for chondrotoxicity following in vitro or in vivo intra-articular exposure to an antibiotic and antiseptic solutions. All agents, study characteristics, and conclusions were extracted and summarized. Results: The initial search resulted in 228 studies, with 36 meeting full inclusion criteria. Overall, chondrotoxicity was not associated with 7 out of 24 (29%) included agents: minocycline, tetracycline, chloramphenicol, teicoplanin, pefloxacin, linezolid, polymyxin-bacitracin. Inconsistent results were noted with 8 (33%) agents: doxycycline, ceftriaxone, gentamicin, vancomycin, ciprofloxacin, ofloxacin, chlorhexidine, and povidone iodine. Chondrotoxicity was evident with 9 (38%) agents, all of which were also dose-dependently chondrotoxic based on reported estimated half maximal inhibitory concentrations (est.IC50): amikacin (est. IC50 = 0.31-2.74 mg/mL), neomycin (0.82 mg/mL), cefazolin (1.67-3.95 mg/mL), ceftazidime (3.16-3.59 mg/mL), ampicillin- sulbactam (8.64 - >25 mg/mL), penicillin (11.61 mg/mL), amoxicillin (14.01 mg/mL), imipenem (>25 mg/mL), and tobramycin (>25 mg/mL). Additionally, certain studies reported chondroprotective effects of doxycycline and minocycline. Conclusion: This systematic review identified antimicrobial and antiseptic agents that may be used in the treatment of septic arthritis. The following agents should be avoided due to their dose-dependent chondrotoxic effects: amikacin, neomycin, cefazolin, ceftazidime, ampicillin-sulbactam, penicillin, amoxicillin, imipenem, and tobramycin. Further studies, especially in human models, are needed to clarify the safety of these medications for human intra-articular use.