Pre-clinical Evaluation of a Third Generation Absorbable Antibacterial Envelope.
Academic Article
Overview
abstract
BACKGROUND: The TYRX absorbable antibacterial envelope has been shown to stabilize implantable cardiac devices and reduce infection. A third-generation envelope was developed to reduce surface roughness with a redesigned multifilament mesh and enhanced form-factor but identical polymer coating and antibiotic concentrations as the currently available second-generation envelope. OBJECTIVE: To compare drug elution, bacterial challenge efficacy, stabilization, and absorption of second- vs. third-generation envelopes. METHODS: Antibiotic elution was assessed in vitro and in vivo. For efficacy against gram+/gram- bacteria, 40 rabbits underwent device insertions with or without third-generation envelopes. For stabilization (migration, rotation), 5 sheep were implanted with 6 devices each in second- or third-generation envelopes. Pre-specified acceptance criteria were <83 mm migration and <90 degrees rotation. Absorption was assessed via gross pathology. RESULTS: Elution curves were equivalent (similarity factors ≥50 per FDA guidance). Third-generation envelopes eluted antibiotics above minimal inhibitory concentration (MIC) in vivo at 2hr post-implant through 7d, consistent with second-generation envelopes. Bacterial challenge showed reductions (p<0.05) in infection with second- and third-generation envelopes. Device migration was 5.5±3.5 (third-generation) vs. 9.9±7.9 mm (second-generation) (p<0.05). Device rotation was 18.9±11.4 (third-generation) vs. 17.6±15.1 degrees (second-generation) and did not differ (p=0.79). Gross pathology confirmed absence of luminal mesh remainders and no differences in peri-device fibrosis at 9 or 12wks. CONCLUSION: The third-generation TYRX absorbable antibacterial envelope demonstrated equivalent pre-clinical performance to the second-generation envelope: antibiotic elution curves were similar, elution was above MIC for 7d, infections were reduced compared to no envelope, and acceptance criteria for migration, rotation, and absorption were met.
