Preclinical evaluation of a third-generation absorbable antibacterial envelope

Abstract

The TYRX (Medtronic) 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. The purpose of this study was to compare drug elution, bacterial challenge efficacy, stabilization, and absorption of second- vs third-generation envelopes. Antibiotic elution was assessed invitro and invivo. For efficacy against gram-positive/gram-negative 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. Prespecified acceptance criteria were <83-mm migration and <90° rotation. Absorption was assessed via gross pathology. Elution curves were equivalent (similarity factors ≥50 per Food and Drug Administration guidance). Third-generation envelopes eluted antibiotics above minimal inhibitory concentration (MIC) invivo at 2 hours postimplant through 7 days, consistent with second-generation envelopes. Bacterial challenge showed reductions (P <.05) in infection with second- and third-generation envelopes. Device migration was 5.5 ± 3.5 mm (third-generation) vs 9. 9 ±7.9 mm (second-generation) (P <.05). Device rotation was 18.9° ± 11.4° (third-generation) vs 17.6° ± 15.1° (second-generation) and did not differ (P = .79). Gross pathology confirmed the absence of luminal mesh remainders and no differences in peridevice fibrosis at 9 or 12 weeks. The third-generation TYRX absorbable antibacterial envelope demonstrated equivalent preclinical performance to the second-generation envelope. Antibiotic elution curves were similar, elution was above MIC for 7 days, infections were reduced compared to no envelope, and acceptance criteria for migration, rotation, and absorption were met.