A prospective, randomized assessment of a novel, local antibiotic releasing platform for the prevention of superficial and deep surgical site infections

Abstract

Background Despite significant advances in infection control guidelines and practices, surgical site infections (SSIs) remain a substantial cause of morbidity, prolonged hospitalization, and mortality among patients having both elective and emergent surgeries. D-PLEX100 is a novel, antibiotic-eluting polymer–lipid matrix that supplies a high, local concentration of doxycycline for the prevention of superficial and deep SSIs. The aim of our study was to evaluate the safety and efficacy of D-PLEX in addition to standard of care (SOC) in preventing superficial and deep surgical site infections for patients undergoing elective colorectal surgery. Methods From October 10, 2018 to October 6, 2019, as part of a Phase 2 clinical trial, we randomly assigned 202 patients who had scheduled elective colorectal surgery to receive either standard of care SSI prophylaxis or D-PLEX100 in addition to standard of care. The primary objective was to assess the efficacy of D-PLEX100 in superficial and deep SSI reduction, as measured by the incidence of SSIs within 30 days, as adjudicated by both an individual assessor and a three-person endpoint adjudication committee, all of whom were blinded to study-group assignments. Safety was assessed by the stratification and incidence of treatment-emergent adverse events. Results One hundred and seventy-nine patients were evaluated in the per protocol population, 88 in the intervention arm [51 males, 37 females, median age (64.0 range: 19–92) years] and 91 in the control arm [57 males, 34 females, median age 64.5 (range: 21–88) years]. The SSI rate within 30 day post-index surgery revealed a 64% relative risk reduction in SSI rate in the D-PLEX100 plus standard of care (SOC) group [n = 7/88 (8%)] vs SOC alone [n = 20/91 (22%)]; p = 0.0115. There was no significant difference in treatment-emergent adverse events. Conclusions D-PLEX100 application leads to a statistically significant reduction in superficial and deep surgical site infections in this colorectal clinical model without any associated increase in adverse events.

Preclinical In-Vivo Safety and Toxicokinetics of D-PLEX100 in an Abdominal Surgery Incision Model in Juvenile Miniature Swine

“…By that, D-PLEX can provide controlled antibacterial activity directly at the surgical site, while keeping systemic antibiotic exposure very low. 9,13 The safety of D-PLEX in adult animals has been demonstrated previously in preclinical in vivo studies in a sternal surgical defect model in New Zealand white rabbits and in an abdominal surgical incision model in miniature swine. Full absorption of D-PLEX was observed after 9 and 6 months in both models, respectively.…”

“…However, this method has limitations in its effectiveness since the local concentration of the given antibiotic at the surgical site may not reach the necessary levels, resulting in ineffective prophylaxis. [7][8][9] The medical conditions known to be associated with lower local concentrations include peripheral vascular disease, obesity, and diabetes. [9][10][11][12] To overcome this hurdle, various techniques for delivering antibiotics directly to the surgical site have been developed.…”

“…[7][8][9] The medical conditions known to be associated with lower local concentrations include peripheral vascular disease, obesity, and diabetes. [9][10][11][12] To overcome this hurdle, various techniques for delivering antibiotics directly to the surgical site have been developed. Such a local drug delivery system is D-PLEX (PolyPid Ltd, Petah Tikva, Israel), which pairs an innovative Polymer-Lipid Encapsulation matriX (PLEX) technology platform with the broad-spectrum antibiotic, doxycycline.…”

Novel Strategies to Prevent Surgical Site Infections

“…The authors concluded that this novel matrix could be a promising addition to current SSI prevention bundles. 6…”

“…No significant differences in adverse events occurred between the two groups. The authors concluded that this novel matrix could be a promising addition to current SSI prevention bundles 6 …”