Prolonged Antimicrobial Durability of a Sodium Mercaptoethane Sulfonate (MeSNA) + Minocycline (M) + Rifampin (R) Combination in an In Situ Melting, Bioabsorbable Wrap for Preventing Tissue Expander Infections Following Breast Reconstruction Surgeries

Background: Tissue expanders (TE) used in breast reconstruction following cancer surgery have reported infection rates ranging from 2.5-24%. Most of these infections occur within 90 days of TE insertion and hypothesized to be caused by post-operative colonization of the TEs. The common practice of peri-operatively irrigating surgical pockets with low-viscosity antibiotic solutions provides ineffective transient prophylaxis. We previously reported a novel method for prolonging prophylaxis via application of solid film (wrap) containing M/R at implantation that subsequently liquefied in situ (at 37⁰C) to a viscous fluid. Here we tested further addition of the cytoprotective agent, MeSNA, previously shown to reduce fibrous capsule formation around TE implants in animals, to the M/R wrap for its ability to further enhance antimicrobial durability in an in vitro model.

Methods: Antimicrobial gelatin-based wraps were formed containing no antibiotic, M (0.1%)/R (0.05%), MesNA (5%), and M (0.1%)/R (0.05%)/MeSNA (5%). One-cm diameter silicone disks cut from TEs were covered with wraps. The disks were incubated with 5x10⁵ CFU/ml clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug resistant Pseudomonas aeruginosa (MDR-PA) in broth containing physiologic concentrations of collagenase. The inoculum was replaced weekly with fresh inoculum for 2 weeks. Each week disks were harvested and adherent organisms enumerated.

Results: Control silicone disks and no-antibiotic gelatin-wrapped disks yielded about 5x10⁴ cfu/disc of adherent bacteria for each challenge organism. Wraps containing M/R completely inhibited all challenge organisms from attaching to the silicone at 1 week (p<0.001), but breakthrough occurred at week 2 for MDR-PA (at a level of 5x10³ CFU/mL). The 5% MeSNA wraps did not inhibit adherence of MRSA or MDR-PA, but M/R/MeSNA wraps completely inhibited attachment of both challenge organisms for 2 weeks (p<0.001). Incorporation of MeSNA visibly decreased the rate of enzymatic dissolution of the wraps.

Conclusion: Addition of MeSNA (the MeSNA/M/R combination) enhanced the durability of antimicrobial efficacy of the M/R antimicrobial wrap against MDR-PA in a physiologic in vitro model.