Safety Profile of Seven-Day Intra-Articular Antibiotic Irrigation for the Treatment of Chronic Periprosthetic Joint Infection: A Prospective Randomized Phase II Comparative Study.

INTRODUCTION: Systemic intravenous antimicrobials yield poor outcomes during the treatment of periprosthetic joint infection because systemic therapy is unable to obtain the minimum biofilm eradication concentration. Therefore, this study evaluated the safety of a novel method of optimized local delivery of intra-articular antibiotics (IAA) when compared to two-stage exchange arthroplasty.

METHODS: This was a Phase II, multicenter, prospective randomized clinical trial of the safety of a seven-day two-stage exchange arthroplasty with IAA irrigation compared to a standard two-stage exchange. The experimental group included irrigation using 80 mg tobramycin daily with a 2-hour soak, followed by hourly irrigation using 125 mg vancomycin with a 30-minute soak via an intramedullary irrigation device. The control group received an antibiotic loaded cement spacer with vancomycin (average 8.4 g) and tobramycin (average 7.1 g, total 16 g antibiotic). Both groups received 12 weeks of systemic antibiotics following Stage 2. Safety measures included: adverse events, peak vancomycin/tobramycin serum concentrations (experimental group), blood transfusion, and mortality. There were thirty-seven patients who were randomized to the experimental group and 39 to control. There was no difference in baseline demographics or comorbidities.

RESULTS: There were no antibiotic medication-related adverse events and 2 serious adverse events (SAEs) related to antibiotic instillation. Of 188 vancomycin peak measurements in the experimental group, 69% had detectable serum level concentrations, with all concentrations well below the maximum acceptable trough threshold of 20 μg/mL. Of the 103 tobramycin peak measurements, 45% had detectable levels, with all below the maximum acceptable peak threshold of 18 to 24 μg/mL. There was no difference in the amount of blood transfused per subject (Experimental: 655 ml versus Control: 792 ml; P = 0.4188). There were two (2) deaths that occurred in each group.

DISCUSSION: The use of IAA is safe with minimal systemic antibiotic exposure. There was no difference in the rates or severity of the SAEs between groups. Further research is being conducted to examine treatment efficacy.