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MedCity Influencers, BioPharma, Physicians
By Noam Emanuel
Surgical site infections (SSIs) are among the most common complications following surgery, occurring in 2-4% of patients undergoing inpatient surgical procedures. Though often treatable, SSIs, which occur at or near a surgical incision shortly after a procedure, significantly increase the likelihood of severe morbidity and even mortality. No matter how skilled the surgeon, SSIs can undo the success of a procedure and adversely impact the health of a patient. As a leading contributor to hospital readmissions, the impact of SSIs on healthcare resources also poses a significant financial burden, propelling scientists and healthcare experts to identify effective preventive measures to reduce SSI rates.
The obvious remedy to warding off an infection at the surgical site is through the administration of antibiotics. But it is not so simple. Standard antibacterial methods used by surgeons today are limited in their effectiveness, as is evident by the prevalence of SSIs. These methods only provide a short exposure to antibiotics which is not always sufficient to eradicate invasive bacteria. Moreover, bacteria can invade the surgical wound during the healing process, and long after surgery when no antibiotic coverage is available. Hence, antibacterial treatments must be reconfigured to extend over a prolonged term to effectively eradicate any invasive bacteria that could result in an SSI.
Rethinking antibiotic administration
The standard of care for the prevention of SSI includes the administration of antibiotics intravenously (IV) within one hour prior to surgery. Prophylactic systemic administration uses significant doses of antibiotics in order to transport the medication through the entire circulatory system to reach the surgical site and maintain effective local concentration levels. However, most of the drug is dispersed to non-relevant organs and only a small fraction of the administered antibiotic dose reaches the wound before being cleared through the kidneys and liver, and then expelled from the body over the course of just a few hours.
Another element to consider is that surgery disrupts the blood supply at the incisional site, which further limits the penetration of the drug into the surgical wound. This highly invasive process can render post-operative administration of antibiotics inadequate in preventing incisional SSI, as it can take several days following surgery for blood flow to be fully resumed at the location of the incision. Furthermore, compensating for the limited effect by elevating the systemic dose of antibiotics, and/or extending the administration period, could increase the risk of overall toxicity to the patient and may boost the generation of antibiotic-resistant bacterial strains.
Uncovering how to make antibiotic therapies more effective in preventing SSI, it is logical to assume that it is not only the selection of antibiotic, but rather the way it is administered to the wound, that determines the treatment’s efficacy. The limited effectiveness of systemic antibiotic administration led physicians to embrace localized therapeutics – but that too has failed to further reduce SSIs rates in high-risk procedures, such as abdominal colorectal resections. To give patients the best chance at healing and avoiding SSIs, while also reducing healthcare costs, we must change our approach. We cannot solely rely on the poor penetration of systemic antibiotics into the incisional site, nor can we mitigate this deficiency by exposing the patient to toxic and extended high dosages of antibiotics.
There is no doubt that localized antibiotic administration is a central and crucial element for any future SSI prevention solution since it can bypass key delivery issues. To be effective, however, local delivery of antibiotics needs to generate sufficiently high concentration levels locally in the incision, and over the entire and extended duration needed to stave off SSI. This includes infections resulting from hospital-acquired antibiotic-resistant bacteria. To achieve that, the localized solution must store an antibiotic reservoir adjacent to the surgery site and release the drug in a controlled manner to deliver long lasting, high concentrations of antibiotics, while maintaining non-toxic systemic exposure.
Currently, localized therapeutic options leave much to be desired and a reform is needed. Today’s localized antibiotic therapeutics come in various forms, such as antibiotic-infused sheets or high doses of antibiotic powder poured directly into the surgical site. However, these solutions demonstrated limited or no further reduction in SSI’s rates and have yet to prove efficacy for SSI prevention over standard solutions – especially in high-risk procedures and when facing challenging antibiotic-resistant bacterial infections.
The key is finding the right localized therapeutic formulations needed for success. Luckily, we are finally making headway. Such therapeutics must leverage cutting-edge technologies to enable simple application of localized, controlled-release mechanisms that stay anchored to the surgical site, deliver effective and safe doses of antibiotics, and subsequently degrade when the pre-determined release period ends – all without any external intervention. In recent years extended-release formulations have been innovated using either polymer or lipid technologies, and with some adjustments they could be the future of localized administration of SSI prevention antibiotics.
The power of layers … done right
Polymer-based drug delivery systems can trap or mix drugs in polymer matrices, making them useful for anchored, attenuated drug release in a desired location. However, polymeric systems by themselves cannot ensure extended drug release, as the release of the drug from such polymer-based delivery systems is often uncontrolled and therefore limited in its ability to ensure constant and sufficient medication concentration to the site over the desired period. Moreover, the polymers are often less equipped to protect the embedded drug from degradation caused by the body’s natural hydration process over time, reducing drug reservoirs needed for a prolonged local effect.
Alternatively, lipid-only drug delivery systems, such as liposomal-based applications, may be better equipped to protect the drug’s reservoir from the body. However, lipid-only drug delivery systems lack key attributes that polymeric systems contain. Ultimately, neither polymer-based nor lipid-based solutions can individually provide anchored, localized drug delivery at customizable, predetermined rates and prolonged release, which are critical attributes needed for improved healing rates.
The power of effective localized therapeutics lies in innovative multi-layer formulations that combine both polymer- and lipid-based technologies. These technologies can trap a therapeutic drug, protect the drug reservoir, and when applied to the tissue, slowly dissolve into the body at the required rate. With these capabilities, such solutions enable extended and effective drug delivery that can withstand, over a period of weeks, minimal systemic exposure. By harnessing the qualities of each of these therapeutic delivery systems, patients can be protected in the lengthy recovery process, even weeks following surgery.
The Covid-19 pandemic has served as a catalyst for evolutionary change in the healthcare sector, leading to the implementation of innovations previously regarded as futuristic. SSI prevention is one of those compelling areas requiring immediate change to help reduce patient morbidity and mortality and relieve a tremendous financial burden from 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, ushering in the revolutionary change in SSI-prevention physicians have been waiting for.
Photo: Motortion, Getty Images
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Dr. Emanuel is the co-founder and chief scientific officer of PolyPid. He received his Ph.D. degree from the Faculty of Medicine at the Hebrew University of Jerusalem.
biopharma nl, surgical site infection
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