Background: The presence of a wound can be anywhere from non-problematic to life-threatening on a severity spectrum, with bacterial infection and resistance playing a major role in the development of chronicity, delaying wound healing. Wound colonization with multiple organisms and the limited number of effective antibiotics place a heavy burden on the healthcare system, with patients going through multiple surgeries during a prolonged hospitalization time. By analyzing the resistance patterns of pluri-bacterial populations and the approach used in managing complex cases, we aim to improve the protocols applied in caring for chronic wounds in our practice and share our experiences and observations. Methods: We designed a retrospective study on 212 diabetic and non-diabetic patients, aiming to evaluate the course of chronic wound treatment in our practice. We focused on the impact that MDR bacteria and diabetes have on surgical outcomes and their role in the healing process. Results: Patients who received empiric antibiotic therapy before being admitted eventually presented with multiple MDR bacteria compared to those who did not receive antibiotics (p = 0.014). The presence of at least one MDR bacteria in the wound bed was associated with ulcers reaching bone (p = 0.02) and was positively correlated with the number of surgeries performed (p < 0.001). Diabetes played a significant role in surgery-related complications (p = 0.02) and hospitalization time (p < 0.001). Conclusions: Proper management of chronic wounds requires a comprehensive, multidisciplinary approach and a thorough understanding of antibiotic usage. To address this need, we have developed and implemented a chronic wound treatment protocol in our clinic, with the goal of discharging patients once their ulcers have been treated and closed. A key summary of the protocol presented is to reduce the incidence of MDR bacteria and improve the patient’s quality of life.