Myth Buster Wound Biofilm
Dr Matthew Malone ‘busts’ the common myths and misconceptions about wound biofilm, and how these are relevant to your clinical practice.
Smith & Nephew Mythbuster Matthew Malone June 3, 2020
0:02 Welcome to Smith & Nephew's Closer to Zero podcast, a bi-monthly podcast with leading experts in wound care hosted by Smith & Nephew, helping healthcare professionals in reducing the human and economic costs of wounds.
0:15 Hello, I'm Ruth Timmins from Smith & Nephew and it's my pleasure to host our inaugural Myth Buster podcast episode today with our very special guest, Dr. Matthew Malone. We have a great discussion centred around dispelling common myths about wound biofilm. Matthew is a leading global expert in wound biofilm and is the current director of research for the Southwest Sydney Limb Preservation and Wound Research academic unit, and we're really pleased to have Matthew with us today.
DR. MATTHEW MALONE:
0:45 Thanks Ruth. It's a pleasure to be here with you today.
0:48 Welcome Matthew and thanks for joining us for the launch of our very first podcast. I know this topic is of great interest to many clinicians and there are many myths about wound biofilm. It's great that we can get your expertise and thoughts and to help us bust a few myths for our listeners
DR. MATTHEW MALONE:
1:05 Yeah, thanks Ruth. It's a great opportunity for me to try and dispel lots of, I think, misconceptions around biofilm. If you're a clinician and you've maybe walked around some of the recent conferences, there is probably not a stand that you pass that doesn't have a product or make a claim against biofilm, and there's a lot of information out there which may not be so accurate. So, it's just great to have 25 minutes or so with you and have a good old chat and see if we can dispel some of the misconceptions around biofilm.
1:44 That's great. Thanks Matthew, and so, I guess one of the first ones perhaps to start with is, are all biofilms bad?
DR. MATTHEW MALONE:
1:51 That's a great question. It's actually something I've asked Thomas Bjarnsholt, who's a leading expert in biofilms from Denmark, I actually asked him whether, you know, he thought all biofilms were bad because I think there's a misconception that if you have biofilm in a wound, it's all doom and gloom and that must be a problem, and so, I asked Thomas, I said, you know, what do you think about this? And, you know, he said to me that basically, you know, not all biofilms are bad, and we can look to nature to provide examples of this, and so, if you look at lakes or aquatic environments and Marine Ecosystems, biofilms actually form the predominant mode in which micro-organisms live. If we look a bit closer to human health and disease and we look at the gut microbiome for example, you know, we've heard a lot about having good gut bacteria. So, they exist as biofilms, and so, we know in human health and disease that there's obviously good biofilms.
So, when it comes to wounds, you know, the question is, are all biofilms bad? The likelihood is that the answer is yes and no, and we'll have, I think, good biofilms in wounds. But I also think maybe some of the reasons why we might see a lot of problems potentially with biofilms in wounds is because of maybe the types of patients that we find them in. We know that our patients are generally not very healthy, typically on the skin. The skin will remain unbroken and you'll have microorganisms on there. But when you breach that skin, you expose potentially otherwise sterile structures that are moist and warm and potentially then attract bacteria. When you add to that the fact that maybe some people don't feel these injuries and therefore might not try and address the problem in a quick time i.e., clean it, you can start to build a picture to maybe potentially why we start to see quite a few problems in the type of cohorts of patients we see.
3:59 OK. Thanks, Matthew. So, another perhaps common misconception is that biofilms are visible to the naked eye observation. So, what are your thoughts on that?
DR. MATTHEW MALONE:
4:09 Yeah, it's quite a funny one actually. I think you have to have a bit of common sense here, and so, you know, if I was to ask you, Ruth, whether you could see bacteria that's, you know, on your keyboard or on your mouse or on your phone or on your kitchen table, you're going to turn around to me and say, no, you can't, unless, you know, you have microscopy vision.
The simple fact is, biofilms are just bacteria, and in that instance, you know, we can't see them. If we look again to nature, OK, maybe there's areas where you can see them, where biofilms have been left untouched for years and years to mature and grow, you know, in rivers, on the stones that are on rivers or, you know, build-up of slurry and things inside pipes where they're not touched. But, you know, wounds are maybe a different story where often than not, they're sort of looked up quite frequently or they're cleaned quite frequently or debrided and so forth, and so, you know, I think that obviously that doesn't give him a chance to build up. So, whether or not we can see biofilms on wounds for me is a big fat no. It's not possible. You cannot see biofilms with naked eye observations.
Some people in the literature have reported that there's potentially things which might tell you there's a biofilm there, you know, there's a slimy layer on the wound or it's a translucent shiny thing on the wound or it's a sort of fibrin slough that you debride it and it comes back really quickly, and the problem with that is, it's all based on rhetoric and there's no real science to prove that that's actually the case. So, for me, no. You cannot see biofilms with your naked observations.
5:55 OK. Thank you, Matthew. So, perhaps another one is that, you know, biofilms are formed only on the wound surface. So, what are your thoughts around that thought?
DR. MATTHEW MALONE:
6:10 Yeah. Look, I think again, you've just got to apply a level of common sense, and here, if you think about bacteria, you know, bacteria don't just sit on the surface of skin or wounds. Well, obviously on the skin they do because we have quite a lot of host barriers. When you breach that skin and you have a wound, microorganisms can colonise into the wound and then can start to spread extracellularly through the tissue. So, we know that bacteria can move from the surface of the wound and go quite deep into the tissue. We know that because I've taken biopsies of wounds and found biofilms at a significant depth. We know that because I've done studies where we've looked at infected bone and we've found biofilm as a cause of chronic osteomyelitis. So, they've got to be able to then spread from a surface to deeper structures. So, the key here really is that these biofilms, they behave in a similar way to planktonic bacteria with regards to, if planktonic bacteria can move down from the surface of a wound deeper, then certainly biofilms will be able to do that, and that obviously then has sort of treatment ramifications with regards for clinicians, maybe, you know, just thinking that they can clean the surface of a wound is enough, and that's unlikely to be true.
7:34 OK, thank you. It's thought that there is only really one type of biofilm in wounds. What do you think about that statement?
DR. MATTHEW MALONE:
7:42 You know, it's the same again. What we know from... Lots of studies were done either through conventional culture or through molecular sequence. It is that the majority of wounds are polymicrobial. What's really interesting, potentially, with biofilm in wounds is that there seems to be sort of a non-random pattern, and by that what I mean is, you know, if you find biofilm in a wound, you very rarely find it on its own. So, you don't just find a wound with biofilm. You'll find a wound that has biofilm but that also has planktonic bacteria in there. The sections of tissue we've taken from studies have found that, well actually, you can find biofilm in one part of the wound and then there'd be nothing in another part. You can find that some of the biofilm in one part of the wound might just be one species like Staph aureus form in the biofilm, and then right next to it you find another aggregate of biofilm, and actually, that's a polymicrobial biofilm. So, the key thing here really is, it's unlikely that, you know, if you get a wound culture and it shows Staph aureus, that that is going to be the only biofilm forming bacteria in that wound, and so, for me, I have to say that the bulk of wounds we see will more than likely have polymicrobial biofilms in them.
9:08 OK. So, you mentioned wound cultures there. So, do wound cultures diagnose biofilm in your experience?
DR. MATTHEW MALONE:
9:16 So, the answer to that is both yes and no. You can culture and grow biofilm, but it takes quite eloquent lab techniques to do that, and your standard clinical microbiology labs will not have setups to grow biofilm from clinical samples. The other key thing here really, I think, is around how you collect those samples. So, most clinicians may take a wound swab. Now, with that, that certainly may not be enough to actually pick up biofilm from a cotton swab from the tissue because obviously they may be adhered to the tissue and be at depth which is deeper than just the wound surface, and so, you know, maybe just taking a swab will be unlikely to actually obtain the biofilm for culturing purposes, and actually, probably the best and most likely way to resolve this is to obtain sections of tissue where you can actually physically remove large sections of biofilm and then sort of grind up tissue and then and implant them out.
So, you may be able to identify some biofilms through wound cultures. Again, that may vary with the type of sampling technique you use, and also, just for clinicians to be a little bit aware that not all bacteria, whether they're in biofilm or not, you can actually cultivate in a lab, and we know that through molecular studies we've done where we've shown that actually lots of bacteria don't culture very well in the lab. So, actually we may not have a full picture of it. So, there's not a straightforward answer.
11:06 OK. Thank you, Matthew. So, quite often silver agents are thought of as highly effective against wound biofilm. So, what would you say about that statement?
DR. MATTHEW MALONE:
11:20 So, look. I think for me, all of this really started in about 2007 and Thomas Bjarnsholt and the Danish group published a paper which was called Silver against Pseudomonas Aeruginosa Biofilms. What this study did was use some really nice in vitro models to look at the bactericidal concentration of silver required to eradicate biofilm, and it was 10 to 100 times higher than the concentrations required to kill planktonic microorganisms, and what they basically found was that the concentration of many silver dressings used for wounds was just far too low to have an effect, therefore, against biofilms.
And since that time, there's probably been an array of studies that have tested biofilm with really varying results. Probably to summarise that, we have actually, my group, published a systematic review where we've looked at all of the available antimicrobial agents used for wound biofilms, and if we look at silver in an in vitro situation, if we combine all of these tests together, we typically find that silver dressings can have a two-log reduction against in vitro biofilms, and you compare that to iodine, which has a five-log reduction and the PHMBs that have a 3.5-log reduction, and then you look at the animal models where silver has a 0.8-log reduction and iodine can demonstrate a 4.5-log reduction and a PHMB of about DR. 2.3-log reduction. Taken collectively, the evidence does seem to suggest that, you know, silvers are really not that effective against mature biofilms.
13:10 OK, thank you. So, is debridement the only treatment needed to remove wound biofilm then?
DR. MATTHEW MALONE:
13:19 So, again, if we look at the evidence as a whole, we've not really been able to find this magic pill that can completely eradicate or sterilise biofilm from wounds, and because of that, in the absence of it, the sort of gold standard treatment is to then try and physically remove biofilm in its entirety, and obviously in the wound care scenario, the best way to do this is through sharp debridement and with sharp debridement, you basically try to physically remove that nidus, that source of infection or biofilm.
The problem we have with it is while it's an extremely aggressive way and highly effective way potentially to remove biofilm physically in this way, you can't see the bacteria. So, clinicians can't appreciate where the biofilm is situated within a wound and what that means is that you may actually leave pockets of bacteria while you've debrided healthy tissue and think maybe it looks really good, and actually, what happens is, you've left the biofilm, which can then re-form and so, what that really has led, the consensus document which we released as part of the expert wound biofilm group in 2017 is to say that debridement really should be followed by other treatments and form this multifaceted approach.
So, you know, you should debride and then cleanse and then use a topical agent and do that quite frequently.
14:50 OK. Thank you. So, are antibiotics effective against biofilm? Often, antibiotics are prescribed. So, what are your thoughts on antibiotics?
DR. MATTHEW MALONE:
15:02 So, if we look at systemic antibiotics or those taken orally or even intravenously against biofilm, the answer again is both yes and no. We've certainly found evidence to show that there seem to be antibiotics that are more effective in treating biofilm such as Daptomycin, Rifampicin, Ciprofloxacin. But again, this is dependent on the types of species and strains of bacteria or fungi that are forming the biofilm. So, there are agents which seem to work, but the variability is obviously depending on the type of biofilm or species that's forming it. Those results may be variable and that may be one of the reasons why, you know, the sort of clinical treatment of biofilms with antibiotics is also fairly variable with regards to outcomes, and as in any other clinical scenario, it's also about the ability of that bacteria to actually reach the target. So, you know, if you've got ischemic disease, the antibiotic may be effective but obviously is just not able to reach the tissues and reach the biofilm.
Conversely to that, are antibiotics effective against biofilm? No. So, biofilm physiology is different than planktonic bacteria that are rapidly dividing. Biofilms have slow growth. They've reduced their metabolism. What this does is sort of reduce the antibiotic targets. So, you know, antibiotics only work on metabolically active cells, and so, if you've got these very slow-growing microorganisms, that reduces their antibiotic targets obviously they're going to have quite a low effect. Other things are that biofilms often, as I said, are polymicrobial. They exist in communities, and what they can do is something really cool. They can start to share lots of the genetic information, particularly with things around antimicrobial resistance.
So, you can find that one species can provide another species with antibiotic resistance genes. There's lots of things that they're sharing within the biofilm. Also, you know, if you've got a polymicrobial biofilm, what you might find is that some species help others. They might possess antibiotic resistance mechanisms or efflux pumps and other things which help protect maybe the weaker bacteria. It was quite interesting from that perspective. So, as a whole, we know that in biofilms, the concentrations of antibiotics often required to eradicate biofilms in in vitro models can be 100 to 1,000 times as therapeutic concentrations required. So, you know, they can be significantly tolerant to many forms of treatment, and antibiotics is one of them.
17:54 OK. Thank you, Matthew. That's really insightful. So, I guess there's lots of information that we've covered there and dispelling some of the common misconceptions maybe around wound biofilm, and we know that it is problematic for clinicians to manage wound biofilm with delayed healing and so on. So, can you summarise what would be your top three tips for managing wound biofilm?
DR. MATTHEW MALONE:
18:18 Yeah, I think clinicians have got to use a multifaceted approach. I think, you know, debridement and physical removal is pivotal and the core of that, so a good standard of care followed by good wound bed cleansing whether or not that's where the sort of a topical wash or just saline alone, and certainly, once you've debrided and prepared the wound bed to then make sure you're using a topical agent that has a proven efficacy. So, if you have debrided and you have potentially missed things, your employing strategy is to try to keep trying to have a go at the biofilm themselves.
My second tip is, you need to do the above frequently, and I think we have to move away where we have these complex chronic infections, of seeing them weekly or every second week for example.
And actually, to get on top of them and tip the balance, you have to see them frequently now, maybe once or twice a week. It's sort of this step-down approach which we talk about in the consensus document, and then lastly, I think that, you know, as a clinician you can't just focus on the microbe. You've also got to look at local host factors and know what the patient needs. You need to make sure whether the patient has been offloaded or whether they have compression therapy, whether they have good glycemic control, etc, and I think then, together doing all of those in a multifaceted step-down approach, maybe you can tip the scales for patients.
19:45 Thank you Matthew. That's given us some really great tips and I think your insights have helped to dispel the myths and move towards a better understanding of wound biofilm, and I hope our listeners can take this information back to clinical practice. So, thank you once again to Matthew for joining us today and our listeners. Be sure to tune in for our next podcast.
20:09 Meet the challenge of biofilm. Antibiotics are ineffective against biofilm, and misuse can lead to resistance. Disrupt biofilms with IODOSORB 1-12 Up to three days of iodine released. For more information, contact your local Smith & Nephew representative or email us at email@example.com
20:33 The information presented in this podcast is for educational purposes only. It is not intended to serve as medical advice. Products listed and outline of care are examples only. Product selection and management should always be based on comprehensive clinical assessment. For detailed product information, including indications for use, contraindications, precautions and warnings, please consult the product’s applicable Instructions for Use prior to use.
21:00 Helping you get close to zero wound biofilm.
1. Fitzgerald DJ, Renick PJ, Forrest EC, et al. Cadexomer iodine provides superior efficacy against bacterial wound biofilms in vitro and in vivo. Wound Repair Regen. 2017;25(1):13-24.
2. Smith & Nephew 2008.IODOFLEX dressings - disruption of a variety of micro-organisms grown in pre-established single and mixed species biofilms. Internal Report. 0804007.
3. Roche ED, Woodmansey EJ, Yang Q, et al. Cadexomer iodine effectively reduces bacterial biofilm in porcine wounds ex vivo and in vivo. Int Wound J. 2019;16(3):674-83.
4. Phillips PL, Yang Q, Davis S, et al. Antimicrobial dressing efficacy against mature Pseudomonas aeruginosa biofilm on porcine skin explants. Int Wound J. 2015;12(4):469-483.
5. Schultz G, Qingpin Y. Microbicidal Effedts of Three Daily Treatments of a Carboxymethylcellulose Silver Dressing or a Cadexomer Iodine on Mature Bactericidal Biofilms Grown on Pig Skin Explants. Poster presented at WUWHS meeting, Florence, Italy, 2016.
6. Skog E, Arnesjo B, Troeng T, et al. A randomized trail comparing cadexomer iodine and standard treatment in the out-patient management of chronic venous ulcers. British Journal of Dermatology. 1983;109:77-83.
7. Troeng T, Skog E, Arnesjo B, et al. A Randomised Multicentre Trial to Compare the Efficacy of Cadexomer Iodine and Standard Treatment in the Management of Chronic Venous Ulcers in Out-Patients. Stuttgart: Schattauer Verlag; 1983.
8. Holloway GA, Johansen KH, Barnes RW, Pierce GE. Multicenter Trial of Cadexomer Iodine to Treat Venous Stasis Ulcer. The Western Journal of Medicine. 1989;151(1):35-38.
9. Malone M, Johani K, Jensen SO, et al. Effect of cadexomer iodine on the microbial load and diversity of chronic non-healing diabetic foot ulcers complicated by biofilm in vivo. J Antimicrob Chemother. 2017;72(7):2093-2101.
10. Hansson C, Persson L-M, Stenquist B, et al. The effects of cadexomer iodine paste in the treatment of venous leg ulcers compared with hydrocolloid dressing and paraffin gauze dressing. International Journal of Dermatology. 1998;37(390-396
11. Nherera LM, Woodmansey E, Trueman P, Gibbons GW. Estimating the Clinical Outcomes and Cost Differences Between Standard Care With and Without Cadexomer Iodine in the Management of Chronic Venous Leg Ulcers Using a Markov Model. Ostomy Wound Management. 2016;62(6):26-40.
12. O‘Meara S, Al-Kurdi D, Ologun Y, et al. Antibiotics and antiseptics for venous leg ulcers (Review). Cochrane Database of Systematic Reviews. 2014 (Issue 1 Art. No.: CD003557).
PhD FFPM RCPS (Glasg)
Matthew is the current Director of Research for the newly established South West Sydney Limb Preservation and Wound Research Academic Unit, and also the Head of Department for the High-Risk Foot Service at Liverpool Hospital in Sydney. Matthew was recently appointed as a senior lecturer, Infectious Diseases and Microbiology, School of Medicine, Western Sydney University, where Matthew completed his PhD Matthew is also a Fellow, Faculty of Podiatric Medicine, Royal College of Physicians and Surgeons Glasgow, a leading researcher in diabetic foot infections and the role of biofilms and is a current member of the International Working Group for the Diabetic Foot (IWGDF) diabetic foot infection guidelines working group. He is also a member of the Global Wound Biofilm Expert Panel, and a member of the Australian Society of Microbiology, Biofilm special interest group.