Amicidin-alpha and Amicidin-beta: Synthetic proteins engineered to prevent and treat infections in surgery and trauma

Author(s):
Joseph Solomkin; George Babcock; Tara Riddle; Caitlin Nurik; Daniel Huang; Shalyn Lane; Doug Looker; Michael Bevilacqua

Background:

Amicidins are synthetic proteins, purpose-built for application to exposed tissues of surgery and trauma. Amicidin-alpha combines barrier properties of structural proteins (keratins, collagens) with microbicidal activity of antimicrobial proteins (cathelicidins, defensins). It is intended for intraoperative use, especially in clean and clean-contaminated procedures, to protect against microbial invasion and thereby decrease risk of surgical site infection. Amicidin-beta combines microbicidal activity with biosurfactant properties. It is for intraoperative and post-operative use, especially in procedures with heavily contaminated or infected tissue, to reduce microbial load and block progression to sepsis. Both products are in GMP manufacturing; Phase 1 clinical trials are planned. Data presented here focus on a rodent orthopedic surgical model used to assess Amicidins.

Hypothesis:

Amicidin-alpha and Amicidin-beta will help prevent and treat surgical site infections, as well as reduce the use of antibiotics.

Methods:

A surgical wound is created on Sprague-Dawley rats to expose the femur and a steel suture placed. Assessments at 24, 48, or 72h include gross observation, histology, and microbiology of wounds, adjacent muscle, and distant organs.

Results:

Amicidin-alpha applied intraoperatively was effective in preventing microbial contamination, as well as in blocking local infection and progression to sepsis. By example with MRSA (10⁷), the combination of intraoperative Amicidin-alpha and systemic cefazolin completely blocked muscle tissue invasion at 24h, whereas cefazolin alone had very modest effect. Amicidin-alpha alone was also found to be highly effective in studies with MRSA and P. aeruginosa.

Amicidin-beta applied intraoperatively (post-contamination) and post-operatively demonstrated multi-log CFU reductions in wound-adjacent muscle and blocked progression to sepsis. By example with P. aeruginosa (10⁷ CFU), Amicidin-beta showed 4 log CFU reduction in muscle at 24h. With a second treatment at 24h, >6 log CFU reduction in P. aeruginosa in muscle tissue was observed at 48h; no microbes were recovered from distant organs. Amicidin-beta with systemic cefazolin was also highly effective.

Conclusions:

Amicidin-alpha with its barrier and microbicidal properties and Amicidin-beta with its anti-biofilm (biosurfactant) properties demonstrated a high level of effectiveness in this model, which mimics the human condition with rapid progression of organisms into adjacent and then remote organs.