Generation of Gelatin-Based Antibiotic-Eluting Conjugates for the Prevention of Surgical Site Infections

Fralish, Zachary D.
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Florida Southern College
Surgical site infections (SSIs) following major surgeries are a growing concern in the healthcare industry. These infections lead to lengthened hospital stays, additional surgical procedures, prolonged antibiotic use, and increased patient morbidity. Current prevention methods include oral administration of antibiotics before surgery, coating of antiseptic agents on incision sites and operating utensils, and systemic administration of antibiotics during surgery. With widespread delivery of antibiotics, there is an increased likelihood of further expansion of antimicrobial resistance. The development of a localized antibiotic-eluting hemostatic agent as a preventive measure will likely improve the efficiency and efficacy of antimicrobial prophylaxis and subsequently reduce the occurrence of SSIs. Therefore, the current investigation identified a methodology to produce a vancomycin-linked hemostatic agent through liquid-phase peptide bond formation. Type B gelatin was incubated with vancomycin and the cross-linking agent 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide (EDC) to allow for internal cross-linking of gelatin and conjugation of gelatin with vancomycin. Infrared (IR) spectroscopy, high pressure liquid chromatography (HPLC), and UV-Vis spectrometry confirmed that vancomycin released from the loaded hemostatic agent maintained its structural integrity following the cross-linking procedure. Additionally, the activity of eluted vancomycin was analyzed through Kirby-Bauer and microdilution assays, and MTT assays assessed toxicity of the released antibiotic. The method described here allows for the production of a biocompatible and active vancomycin-eluting hemostatic agent for the prevention of SSIs. Beyond vancomycin, this methodology was expanded to produce hemostatic agents that elute daptomycin, ceftazidime, and ceftibuten. Incorporation of this technology into post-operative procedures may expedite surgical protocols, limit cost burdens, and decrease mortality rates associated with SSIs.
Honors Thesis Spring 2020
Medical care, Surgery, Vancomycin, Antibacterial agents, Postoperative care, Surgery -- Complications