Local prolonged release of antibiotic for prevention of sternal wound infections postcardiac surgery—A novel technology

Abstract

Introduction Sternal wound infection (SWI) is a devastating postcardiac surgical complication. D‐PLEX100 (D‐PLEX) is a localized prolonged release compound applied as a prophylactic at the completion of surgery to prevent SWI. The D‐PLEX technology platform is built as a matrix of alternating layers of polymers and lipids, entrapping an antibiotic (doxycycline). The objective of this study was to assess the safety profile and pharmacokinetics of D‐PLEX in reducing SWI rates postcardiac surgery. Method Eighty‐one patients were enrolled in a prospective single‐blind randomized controlled multicenter study. Sixty patients were treated with both D‐PLEX and standard of care (SOC) and 21 with SOC alone. Both groups were followed 6 months for safety endpoints. SWI was assessed at 90 days. Results No SWI‐related serious adverse events (SAEs) occurred in either group. The mean plasma Cmax in patients treated with D‐PLEX was about 10 times lower than the value detected following the oral administration of doxycycline hyclate with an equivalent overall dose, and followed by a very low plasma concentration over the next 30 days. There were no sternal infections in the D‐PLEX group (0/60) while there was one patient with a sternal infection in the control group (1/21, 4.8%). Conclusion D‐PLEX was found to be safe for use in cardiac surgery patients. By providing localized prophylactic prolonged release of broad‐spectrum antibiotics, D‐PLEX has the potential to prevent SWI postcardiac surgery and long‐term postoperative hospitalization, reducing high‐treatment costs, morbidity, and mortality.

Assessment of the impact of intravenous antibiotics treatment on gut microbiota in patients: Clinical data from pre-and post-cardiac surgery

“…The incidence of SSI in cardiac surgery is across a broad range. This complication is associated with an increase in the duration of hospitalization, mortality, and economic burden (Frenette et al, 2016;Gudbjartsson et al, 2016;Schimmer et al, 2017;Kachel et al, 2020;Liu et al, 2021). The incidence of readmission and mortality for SSI patients is about 46% and 1-14%, respectively, and the cost of treatment is 2.5 times higher than for non-SSI patients (Frenette et al, 2016;Gudbjartsson et al, 2016).…”

“…Clinical practice guidelines for antibiotic prophylaxis provide some recommendations in cardiac surgery (Hamouda et al, 2015;Eckardt et al, 2018). Periprocedural antibiotics are necessary to prevent infection post-cardiac surgery (Gudbjartsson et al, 2016;Schimmer et al, 2017;Kachel et al, 2020;Surat et al, 2021).…”

Antimicrobial Formulation of a Bacterial Nanocellulose/Propolis-Containing Photosensitizer for Biomedical Applications

“…The result of a longer release is interesting, considering the topical application of the formulations. Once the action of hydrogels is extended, it is possible to promote gradual bacterial inhibition, which can facilitate treatment and wound healing [ 72 ].…”

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

“…More recently, a Phase 2b trial studied the use of a bioresorbable, modified-release gel containing a combination of vancomycin and gentamicin also failed to demonstrate a significant benefit in SSI reduction [ 24 ]. Of the postulated reasons for these findings, the authors note the need for “rethinking of the proposed drug formulation.” The study notes the duration of the gel at approximately 48 h, which is remarkably shorter than the roughly 700 h duration for D-PLEX [ 9 ]. While formally planned studies are certainly necessary for further validation, it is interesting to postulate the utility of a prolonged-eluted locally applied antibiotic treatment option such as D-PLEX as an addition to current standard prophylactic recommendations.…”

“…1 ) for the prevention of superficial and deep SSIs. This PLEX platform contains a matrix of alternating layers of polymers and lipids, which forms a protected reservoir and enables a localized, continuous release of doxycycline for a period of 30 days [ 8 , 9 ]. Here, we report a Phase 2 multi-center single-blind study evaluating the safety and efficacy of D-PLEX in addition to SOC in preventing superficial and deep surgical site infections for patients who have elective colorectal surgery.…”