Triclosan, Often Decried, May Have a Good Side – Treatment of Cystic Fibrosis Infections

Maybe you had the experience of wading through a creek and struggling to keep your balance on the smooth rocks, or forget to brush your teeth in the morning and feel a liner viscous in the mouth. These are examples of bacterial biofilms that are found wherever a surface is exposed to bacteria in a humid environment.

In addition to causing falls in water courses or creating unhealthy teeth, biofilms can cause big problems. Biofilms, multicellular communities of bacteria that can grow on a surface enclosed in their own self-produced silt matrix, can prevent immune cells from engulfing and killing bacteria or preventing antibodies from binding to their surface.

In addition, bacteria in a biofilm resist destruction by antibiotics because of the sticky nature of the matrix and the activation of inherent resistant mechanisms, such as slow-growing cells or the ability to extract the antibiotics from the cell.

Biofilms are one of the major growth patterns of bacteria, but all clinically used antibiotics have been developed against planktonic bacteria swimming freely. That's why they do not work well against biofilms.

My laboratory studies how and why bacteria produce biofilms, and we develop new therapies to target them. Because antibiotic resistance is the most problematic aspect of biofilms during infections, we sought to identify new molecules that could improve the activity of antibiotics against these communities.

We have discovered that an antimicrobial that recently got a bad name for overuse in many household products could be the secret sauce to kill biofilms.

The hunt for antibiotic suramazing

find such compounds, we developed a test to grow plates of 384 tiny biofilms of the bacterium Pseudomonas aeruginosa . We did this to screen for molecules that enhance destruction by the antibiotic tobramycin. We chose this bacterium and this antibiotic as test subjects because they are commonly associated with lung infections and treatment for cystic fibrosis.

People with CF are particularly vulnerable to biofilm infections. These infections often become chronic in the lungs of cystic fibrosis patients and are often never eliminated even with aggressive antibiotic therapy.

After analyzing 6,080 small molecules in the presence of tobramycin, we found several compounds demonstrating the activity of antibiotic improvement. sought. Triclosan antimicrobial has aroused particular interest because it has been widely used in household products such as toothpaste, soaps and hand sanitizers for decades, indicating that it could be used safely at home. patients with cystic fibrosis. Triclosan has also gained a bad reputation because of its over-exploitation, and states like Minnesota have banned these products. The Food and Drug Administration banned its use of soaps in September 2016. This decision was not based on safety concerns, but rather because the companies that made these products did not show more microbial destruction when triclosan was added.

Another fact that piqued our interest is that P. aeruginosa is resistant to triclosan. Indeed, treatment with tobramycin or triclosan alone had very little activity against P. aeruginosa biofilms, but we found that the combination was 100-fold more active, killing more than 99 percent of the bacteria.

We further investigated this combination and found that it worked against P. aeruginosa and other bacterial species isolated from the lungs of cystic fibrosis patients. The combination also significantly improved the rate of destruction so that at two hours of treatment, virtually all the biofilm is eradicated.

Our efforts are now focused on the preclinical development of the tobramycin-triclosan combination. In the case of cystic fibrosis, we expect that patients will inhale these antimicrobials as a combination therapy, but they could also be used for other applications, such as non-healing diabetic wounds.

Although questions about the safety of triclosan have emerged in the mainstream media, dozens of studies, including in humans, conclude that it is well tolerated, summarized in this extensive 2009 European report. My laboratory strongly agrees that triclosan has been significantly overused, and it should be reserved for fighting life-threatening infections.

The next stages of development are to initiate studies of safety, efficacy and pharmacology. And up to now, our own studies indicate that triclosan is well tolerated when it is administered directly to the lungs. We hope that in the near future, we will have enough data to initiate clinical trials with the FDA to test the activity of this combination in people with biofilm-based infections.

We believe that our approach to enhancing biofilm activity with the addition of new compounds will increase the utility of currently used antibiotics. The study of how these compounds work will also shed light on how bacterial biofilms resist antibiotic therapy.