Clinicians treating foot ulcers are regularly faced with the decision of what to use on the wound if it has delayed healing. Recently, this decision has become more challenging with our new understandings on biofilm that further delays healing and promotes infection. These understandings have led to the development of new antimicrobial wound solutions backed by laboratory evidence to cleanse wounds and kill biofilm. Yet, while these solutions may work on biofilms in a lab, do they work in the clinic? And what is the difference between their effects in the lab, on skin substitutes and on real patients? Until now we didn’t know; but that was before DFAs Matthew Malone and his team decided to find out.
Matthew’s team at Liverpool Hospital has been at the cutting edge of biofilm research over the last few years. Biofilm are complex polymicrobial communities that reside on the wound if left unchecked. What they cleverly did in this world first study published in the Journal of Antimicrobial Chemotherapy is test these wound solutions on mature biofilm grown in the lab on plastic plates (‘in vitro’), on explanted pig skin grafts (‘ex vivo’) and on diabetic foot ulcers of ten patients (‘in vivo’). The solutions were ones typically used in clinics around the world, including:
- Woundaid Woundwash, a surfactant-based Melaleuca oil
- Prontosan, a surfactant-based antimicrobial solution with polyhexamethylene biguanid
- Microcyn, a superoxidized solution
- Betadine, a povidone iodine antiseptic solution5.
- Chlorhexidine &
They also tested these solutions using application times more in line with clinical application times. They did this because many of the products tested in lab based environments are applied to the biofilm continuously for up to 24 hours and we know in clinics they are more likely used for minutes not hours. So they applied these solutions once for 15 minutes in the lab; 12 times for 10 minutes over 24 hours on the explanted pig skin graft; and for 15 minutes every day for 7 days on the patient’s ulcers.
However, it should be noted here that not all products were tested in each environment. The authors stated that they did not have the funds to use all products in all environments so they chose the products they thought were most typically used in clinics for the pig skin and patient wounds. Therefore, while all products were tested in the lab, only Microcyn and saline was used on the pig skin graft, and Woundaid on the patients’ ulcers.
In short, the authors found “the performance of these solutions is poor when challenged against mature biofilms using short exposure times that mimic real clinical use”. However, that simple statement does not do their findings justice. They also found that more traditional solutions such as Betadine and Chlorhexidine worked well in reducing biofilm in the lab; whilst the new-generation solutions such as Woundaid and Prontozan performed poorly and no better than saline in the lab. Microcyn however, which is neither a traditional nor new-generation solution was also effective in the lab; but, it performed poorly on the explanted pig skin biofilm, as did the Woundaid on the patient ulcers.
This study’s findings shine a bright new light on the effect of wound solutions on biofilm. First, they indicate that existing laboratory testing protocols for wound solutions on biofilm does not mimic clinical environments. This suggests a need for the development of minimum protocol standards in terms of biofilm grown and exposure times when testing in labs. Second, wound solutions that were effective in the lab were not as effective on the pig skin. This suggests that biofilm grown on pig skin (that is similar to human tissue) penetrates into the tissue deeper beneath the wound surface and is a more complex structure than biofilm simply grown on a plastic plate in the lab. Third, we need much more testing of these products in clinically relevant environments and on patient’s wounds before we can confirm their effectiveness, which isn’t always easy to do.
While there were many strengths to this study – they compared different wound solutions for clinical relevant times in different environments on mature biofilm grown to contain the typical biofilm forming agents of Pseudomonas and Staphylococcus – they were also some limitations. These limitations included: they did not test the more traditional solutions on the pig skin or patient wounds which would have shone much more light on if they were effective in these environments, and they only tested the new-generation solution of Woundaid on a limited number of patients.
Although this study highlights the limitations of testing antimicrobial solutions on biofilm in a lab, it recommends we shouldn’t simply disregard lab findings. The authors suggest we could use these lab findings as a screening test to determine if solutions may be effective in skin substitute environments. If they are then effective on skin substitutes such as pig skin, then we should trial them on patients. If they are not effective in the lab they are most unlikely to be effective on patients.
We dare say this world-first Australian study may inform the future minimum protocol standards to test antimicrobial solutions in future. And hopefully then we will begin to know with much more certainty if they are effective on clinical biofilms and on improving diabetic foot ulcer healing in our patients.