Effects of Bromelain-Based Enzymatic Debridement on Biofilm and Microbial Loads in Venous Leg and Diabetic Foot Ulcer Patients

Dr. Robert Snyder shares key details from his original research paper, “An Open-label, Proof of Concept Study, Assessing the Effects of Bromelain-Based Enzymatic Debridement on Biofilm and Microbial Loads in Patients with Venous Leg and Diabetic Foot Ulcers.” Read the full paper here.

Transcript

Robert Snyder, DPM, FACFAS, CWS:

Hello, my name is Dr. Rob Snyder. I'm Dean and professor of Clinical Research at Barry University School of Podiatric Medicine. And I'm going to talk today a little bit about a paper which was just published on the use of topical bromelain for the treatment of biofilm in patients with chronic wounds.

So, in thinking about why this paper was initiated in the first place, we all know from the literature that greater than 90% of all wounds, including venous leg ulcers have 90% biofilm and 100% of biofilm is noted in patients with diabetes. And, of course, when patients are not healing with appropriate algorithm care, very often biofilm is the culprit, because it's creating a chronic state of inflammation.

It was a very interesting article that was published based on some in vitro data. It was done out of San Antonio on a Staph aureus biofilm, and they looked at 4 different types of enzymes, 1 of which was bromelain. And what they found that bromelain had a 98% reduction in biofilm when utilized in this study. So, because we were looking very seriously at a topical bromelain-based therapy, we felt this was important to carry out in an in vivo model.

So what we did was we looked at 3 sites in the US. It was an open-label study. We looked predominantly at 12 patients with diabetic foot ulcers and venous leg ulcers. It was a prospective open-label, single-arm pharmacologic study. And we were looking at several endpoints. Number 1, we wanted to make certain that it was safe and efficacious. We wanted to see the effect it had on biofilm. We also wanted to see the effect it had on planktonic bacteria, and lastly, wound progression. So, we did also look at biomarkers. We did not find that biomarkers change dramatically, but again, this was done over such a short period of time that this was not surprising.

The results were very, very significant. First and foremost, 70% of patients achieved complete debridement within 8 applications. And the average number of applications was 3.9 or about 4 applications. Sixty-five percent of the patients had a reduction in bioburden; 35% of the patients had a decrease in wound size by the end of a 2-week follow-up. And very importantly, 100% of those patients that had biofilm in their wounds had complete reduction of that biofilm.

So, what we did, in essence, is we took 3 mm punch biopsies of the wounds before we applied the topical bromelain-based enzymatic debriding agent to the wound. We waited for the wound to be completely debrided, and then we took another 3 mm punch biopsy.

Another thing that we did was in order to ensure that we were biopsying the right place, we used the MolecuLight device that would fluoresce bacteria so that we knew exactly what we were looking at and what we were going to sample. And of course, we sent those samples to a biofilm lab, but not only to evaluate for the biochemistry, but also to look under a confocal scanning laser microscopy to make certain that we were actually seeing biofilm. They also used the classification, which was based on 0 to 5, 0 being no biofilm, and 5 being a significant amount or a continuous film of microorganisms. And what they found, as I had mentioned earlier, in those individuals, in those wounds rather, that had biofilm present, there was a complete resolution of that biofilm.

So, it was a very significant result. I found that it very, very likely will fill a gap that we currently have. Biofilm is very difficult to treat. It's very clear from the literature that even when you do an extensive debridement of the biofilm bacteria, that it will reform a mature biofilm within 72 hours. Greg Schultz did a very interesting study looking at a step-down model where he's very aggressive on the front end and then over a period of days and weeks can then go to a standard of care model. But what's very often missing is the fact that you don't have continuous debridement throughout that period. So, what this therapy could conceivably do is create that dynamic where when the product is being applied, that biofilm is constantly being debrided in an enzymatic format. So, this could have a significant benefit, particularly in those patients that have recalcitrant wounds.

What led me to create the study was the fact that we knew that biofilm was a very significant issue in those individual patients that were not healing with appropriate care. And again, we looked at that study done out of San Antonio with the Staph aureus biofilm, and there was such a dramatic response to bromelain, as I said, 98%, that it just made sense to move to the next level and study this topical agent in an in vivo model. So that was really the catalyst for doing this.

The most surprising result, I think, that I found was the fact that there was a dramatic decrease in wound size at the end of the 2-week follow-up. We were looking at safety and we were looking at both planktonic and biofilm bacteria. But it was very surprising that even in this short period of time, it was a dramatic decrease in wound size. So, it is showing that this bromelain-based topical agent is having an effect on wound healing as well.

I think it's very important that biofilm be kind of at the top of mind, because there are many, many wounds that will not heal. And often the culprit is the biofilm. And if we're not treating this appropriately, or if we have nothing in our toolboxes to really treat this, then these will lead to very recalcitrant wounds, which ultimately can become infected. And particularly in the diabetic population, that could be devastating, leading to sepsis, infection, limb loss, and even death. So it's very, very important that we evaluate this particular aspect of the wound very, very carefully. And again, at this point in time, there really are not many topical agents that really will help in this regard. They are looking at silver products, they're looking at cadexomer iodine, they're looking at surfactants, but nothing really has come to the forefront as significant as this study that we did looking at a bromelain-based topical agent.