A new approach to the management of surgical site infections: use of multilayer formulations in sustained-release antibiotics

Surgical site infections (SSIs) are among the most common complications after surgery, occurring in 2-4% of patients undergoing hospital-based surgeries. Although often treatable, SSIs, which occur at or near a surgical incision soon after surgery, greatly increase the likelihood of severe morbidity and even mortality. Regardless of the skill of the surgeon, SSIs can negate the success of a procedure and negatively impact a patient’s health. As the largest contributor to hospital readmissions, the impact of SSIs on healthcare resources also represents a significant financial burden, driving scientists and healthcare experts to identify effective preventative measures to reduce rates of ISO.

The obvious remedy to ward off infection at the surgical site is the administration of antibiotics. But it is not that simple. The standard antibacterial methods used by surgeons today are limited in their effectiveness, as evidenced by the prevalence of SSIs. These methods provide only a short exposure to antibiotics which is not always sufficient to eradicate invading bacteria. Additionally, bacteria can invade the surgical wound during the healing process and long after surgery when no antibiotic coverage is available. Therefore, antibacterial treatments should be reconfigured to span an extended duration to effectively eradicate any invasive bacteria that could lead to SSI.

Rethinking the administration of antibiotics

The standard of care for the prevention of SSI includes the administration of intravenous (IV) antibiotics within one hour before surgery. Prophylactic systemic administration uses large doses of antibiotics to transport the drug through the entire circulatory system to reach the surgical site and maintain effective local concentration levels. However, most of the drug is dispersed to irrelevant organs and only a small fraction of the administered antibiotic dose reaches the wound before being eliminated by the kidneys and liver and then expelled from the body in just a few hours.

Another consideration is that surgery disrupts the blood supply to the incision site, which further limits drug penetration into the surgical wound. This highly invasive process may make postoperative administration of antibiotics inadequate to prevent incisional SSI, as it may take several days after surgery for blood flow to fully resume at the incision site. Moreover, compensating for the limited effect by increasing the systemic dose of antibiotics and/or prolonging the period of administration could increase the risk of overall toxicity for the patient and stimulate the generation of antibiotic-resistant bacterial strains.

In discovering how to make antibiotic therapies more effective in preventing SSI, it is logical to assume that it is not just the choice of antibiotic, but rather how it is delivered to the wound, that determines effectiveness. of the treatment. The limited effectiveness of systemic antibiotic delivery has led physicians to adopt localized therapies – but this has also failed to further reduce SSI rates in high-risk procedures, such as resections abdominal colorectals. To give patients the best chance of recovery and avoid SSIs, while reducing healthcare costs, we need to change our approach. We cannot rely solely on poor penetration of systemic antibiotics into the incision site, nor mitigate this impairment by exposing the patient to prolonged toxic high doses of antibiotics.

There is no doubt that localized delivery of antibiotics is central and crucial to any future SSI prevention solution, as it can circumvent key delivery issues. However, to be effective, local administration of antibiotics must generate sufficiently high concentration levels locally in the incision, and over the extended duration necessary to avoid SSIs. This includes infections resulting from nosocomial antibiotic resistant bacteria. To achieve this, the localized solution must store a reservoir of antibiotic adjacent to the surgical site and release the drug in a controlled manner to deliver sustained high concentrations of antibiotics, while maintaining non-toxic systemic exposure.

Currently, localized treatment options leave something to be desired and reform is needed. Today’s localized antibiotic treatments come in a variety of forms, such as antibiotic-infused leaves or high doses of antibiotic powder poured directly into the surgical site. However, these solutions have demonstrated limited or no additional reduction in SSI rates and have yet to prove their effectiveness for SSI prevention compared to standard solutions – particularly in high-risk procedures and in the face of drug-resistant bacterial infections. difficult antibiotics.

The key is finding the right localized therapeutic formulations needed for success. Fortunately, we are finally making progress. These therapeutics must leverage state-of-the-art technologies to enable simple application of localized controlled release mechanisms that remain anchored to the surgical site, deliver effective and safe doses of antibiotics, and then degrade at the end of the predetermined release period – all without any outside intervention. In recent years, sustained-release formulations have been innovated using polymer or lipid technologies, and with a few tweaks, they could be the future of localized delivery of SSI-preventing antibiotics.

The power of layers… well done

Polymer-based drug delivery systems can entrap or mix drugs in polymer matrices, making them useful for anchored and attenuated drug delivery at a desired location. However, polymer systems alone cannot provide sustained drug release, as drug release from these polymer-based delivery systems is often uncontrolled and therefore limited in its ability to provide drug concentration. constant and sufficient on the site for the desired period. Additionally, polymers are often less equipped to protect the incorporated drug from degradation caused by the body’s natural hydration process over time, reducing the drug reservoirs needed for sustained local effect.

Alternatively, lipid-only drug delivery systems, such as liposome-based applications, may be better equipped to protect the body’s drug reservoir. However, lipid-only drug delivery systems lack the key attributes that polymer systems contain. Ultimately, neither polymer-based solutions nor lipid-based solutions can individually provide anchored and localized drug delivery at customizable, pre-determined rates and sustained release, which are critical attributes needed to improve patient outcomes. cure rate.

The power of effective localized therapeutics lies in innovative multi-layered formulations that combine both polymer and lipid-based technologies. These technologies can trap a therapeutic drug, protect the drug reservoir, and when applied to tissues, slowly dissolve in the body at the required rate. With these capabilities, these solutions allow for prolonged and effective drug delivery that can withstand, over a period of weeks, minimal systemic exposure. By harnessing the qualities of each of these therapy delivery systems, patients can be protected during the long recovery process, even weeks after surgery.

The Covid-19 pandemic has served as a catalyst for evolutionary change in the healthcare sector, leading to the implementation of innovations previously considered futuristic. SSI prevention is one of those compelling areas requiring immediate change to help reduce patient morbidity and mortality and alleviate the enormous financial burden of hospital care. Physicians may soon have a solution that could be ideal for preventing SSI with a combined multi-layered system that provides the surgical site with controlled and continuous delivery of antibiotics. As we determine the best use cases for this multi-layered matrix to ensure its safe and effective use as a drug delivery vehicle, we can expect support from the transformative healthcare industry for its implementation. implemented, ushering in revolutionary change in SSI prevention. expected.

Photo: Motortion, Getty Images

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