Incisional microenvironments and reduction in SSIs in patients treated with a local doxycycline-eluting formulation
Author(s):
Noam Emanuel; Goldi Kozloski; Anthony Senagore
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 undergoing both elective and emergent surgeries. Patients undergoing colorectal surgery are at increased risk for SSIs. D-PLEX100 is a novel, drug-eluting polymer-lipid matrix that supplies a high, local concentration of doxycycline for approximately four weeks with minimal systemic drug exposure.
Hypothesis:
The objective of this analysis was to evaluate SSI reduction and identify the causative pathogens found within the postoperative soft tissue infection to determine variations in the surgical wound microenvironment following administration of D-PLEX100.
Methods:
Patients undergoing elective colorectal surgery were randomized 1:1 to D-PLEX100 plus Standard of Care (SOC) or SOC alone (ClinicalTrials.gov identifier NCT03633123). All patients received prophylactic IV antibiotics 30-60 minutes prior to surgery. Patients randomized to the investigational arm received D-PLEX100 at the time of closure based on the length of surgical incision (5-10 cm = 5g D-PLEX100 (5g D-PLEX100 contains 54.6 mg doxycycline), 11-20 cm = 10g D-PLEX100, >20cm = 15g D-PLEX100). The SSI rate within 30 days post-index surgery was evaluated. Pre- and post-treatment bacterial colonization analysis was assessed by rectal swab, and organisms were identified and isolated from adjudicated incisional SSIs. Systemic doxycycline plasma concentrations were assessed at various post-operative time points.
Results:
There was a 64% relative risk reduction in SSI rate in the D-PLEX100 plus SOC group (N=7/88 [7.9%]) vs SOC alone (N=20/91 [21.9%]); p<0.05. Causative organisms from SSI wounds were similar between study arms. There was no significant difference in colonization with multi-drug resistant organisms (MDROs) between groups based on rectal swabs. The maximum systemic doxycycline exposure (mean Cmax) was 183.04 ng/ml for patients treated with 15g D-PLEX100 (maximum dose), significantly lower than the 5,100ng/ml found after a standard 200mg oral dose.
Conclusions:
These data demonstrated that the addition of D-PLEX100 to the SSI SOC prophylaxis regimen in elective colorectal surgery provided a 64% reduction in SSIs and importantly this was achieved without affecting the incidence of postoperative colonization by MDROs. As such, D-PLEX100 may be a promising addition to established colorectal SSI bundles for reducing SSIs without the risks associated with systemic antibiotic exposure.