A Blind Spot in an FDA Standard Leaves Significant Bacterial Survivors After Chlorhexidine Gluconate Preoperative Skin Preparation

My name is Hannah Duffy. I'm from the University of Utah. I'm a PhD student in the Department of Biomedical Engineering. I work under Dr. Dustin Williams in the bone and biofilm lab. Surgical site infections are really interesting, and actually what ticked us off on this whole process now is that the culprits for surgical site infection mirror exactly the natural flora of human skin. So this means that in your shoulders, your neck and the chest area, P. acnes is often the most common culprit. But staphylococcus epidermis or staphylococcus aureus is a much more common in the lower extremities like the knee and foot. And so with this, we were able to see a pattern of where the surgical site infection occurred, and then what the culprit was. And this pattern could then be correlated to patient's own endogenous flora. It has been reported recently that between 70% and 95% of surgical site infections are actually caused by endogenous patient flora.

It makes up the largest contribution greater than the air, the patient, the mask, any outside contaminants, air flow, or the surgeon themselves, which is really fascinating and potentially pretty concerning. So in this model, this is a preclinical model. We used pigs. We took seven pigs. We used an N of five per treatment group. On the back of each pig, we compared two bacterial sampling methods. Now, these methods are what I will refer to as the cup scrub method and the tissue blend method. The cup scrub method is a standardized method that the FDA requires for a presurgical skin preparation to be approved. So this is any of your off the shelf presurgical skin products such as chlorhexidine gluconate, maybe Betadine, any of those one stick click applicators. Those would have to be approved by this process. And the way this process works is a sterile cup is applied directly to the surface of the skin.

So just a cylinder is pushed down, and then it's filled with broth, and then a little small sterile spatula is put in and scraped along the surface of the skin. Then the bacteria, which has been suspended into the broth is then taken out, serially diluted, and then quantified. Then this resulting bioburden gives an indication as to how much bacteria is in the skin. Now, this method, unfortunately, fails to consider the bacteria underneath the surface of the skin, hence a blind spot in an FDA standard, which could be of some concern. So in this method, which I will call the tissue blend method, full thickness tissue samples of 16 centimeters squared are excised. Imagine like a large biopsy is taken out. Obviously, this is not appropriate for human patients, and thus the preclinical animal model has been used in this case. Then the tissue sample is then blended and then serially diluted, and then quantified in order to determine exactly the number of bacteria both on the surface and underneath the surface of the skin.

The results of this study I'll differentiate between the two methods that we have previously talked about. The first is the cup scrub method, using chlorhexidine gluconate, a very common healthcare antiseptic, chlorhexidine gluconate eradicated almost all of the bacterial bugs on the surface of the skin. However, using the tissue blend method when the full thickness skin samples were used, significant bioburden resulted. Thus, we have a discrepancy between the cup scrub method and the tissue blend method. Now, the significance of this result goes beyond the chlorhexidine gluconate and also to our control samples. Our control samples were not treated with antiseptic. When we compare the control tissue blend method samples with the chlorhexidine gluconate treated tissue blend samples, we get a statistically insignificant difference. This means that chlorhexidine gluconate is not diffusing down into the skin, and perhaps more microbes than we may might think are surviving this presurgical skin preparation.

I think it's utmost importance that we consider the way that we prepare patients for surgery. When a patient goes into the OR, they are wheeled in, often a few minutes later, a resident, a medical student, or maybe the surgeon themselves will perform an expeditious skin prep, something that lasts anywhere from 20 seconds to maybe a couple of minutes. Often, with the time of the or being constrained, it is difficult to wait sufficient time for this antiseptic to dry or to penetrate as needed. Thus, surgeons may begin a surgery prior to the time when the antiseptic has fully worked. Additionally, I have personally observed surgeries where the antiseptic preparation may be insufficient. Perhaps a medical student has missed a spot or perhaps the surface area of the patient exceeds the quantity that a simple ChloraPrep would cover. In these circumstances, it is especially important to educate the people who are performing the presurgical skin preps, that they do so adequately and with enough time that the presurgical skin prep may dry.

My lab is also working on the next generation of skin prep technology to solve the problem of diffusion and dwell time. We need these antiseptics such as chlorhexidine gluconate, iodine, and others to penetrate further into the skin, into the hair follicles and sebaceous glands. In order to do this, we are looking into novel treatment strategies, and we are excited about promising results that will be forthcoming coming. The true crux of the surgical site infection problem is the anatomical location of where bacteria are located. Bacteria are located on the stratum corneum, the very surface of the skin, the hair follicles, down the hair follicle track, and at the hair follicle bulb, and also in sweat glands and sebaceous glands. These are anatomical features that are located several millimeters underneath the surface of the skin, and it's worth noting that antiseptics used today are not sufficiently penetrating the skin.