The new combined medicinal therapy offers hope for the treatment of chronic wound infections

Researchers at the University of Oregon have tried a new combined pharmaceutical treatment that could disassemble the difficult bacteria that reside in chronic wound infections.

Their findings, published on September 29 in the magazine Applied and environmental microbiologyThey illuminate ways to develop more effective antimicrobial therapies that promote healing in chronic wounds. Such treatments could also help reduce the risk of serious infections that sometimes lead to amputations, such as diabetic legs.

Finished by the National Institutes of Health, the approach mates long -known substances that do not only do little against hard for treatment pathogens in chronic wounds, namely the Pseudomonas aeruginosa bacterium. But with the addition of small doses of a simple molecule called chloride to standard antibiotics, the combination proved 10,000 times more effective in killing bacterial cells in the laboratory than the antibiotics of a drug. This type of power reduced the dose of medicines required to kill P. aeruginosa.

If the findings can be translated into humans, they could help reduce the time that patients should be in antibiotics and reduce the dangers of toxicity, said Melanie SPERO, Assistant Professor of Biology at UO College of Arts and Sciences and Senior Author.

Although investigated here in the context of chronic wound infections, the strategy may have a promise to tackle resistance to antibiotics.

I think the combinations of drugs will be a critical approach that helps us fight the rise of antibiotic resistance. Finding synergy examples between the antimicrobials already on the market will be truly valuable. And we have to dig further the mechanisms behind why they work well together. ”

Melanie SPERO, Assistant Professor of Biology at UO College of Arts and Sciences

Challenges in the treatment of chronic wound infections

A chronic wound is an injured tissue that has not begun to heal within a regular time frames of four to 12 weeks. The most common type is a diabetic foot ulcer, said SPERO, which is an open wound on the underside of the foot formed by poor circulation, prolonged pressure and lack of sensation.

According to a study published by the American Diabetes Association, about 1 in 4 people with type 2 diabetes develop foot ulcer and over half of these cases are infected.

“An active infection is the most common complication that prevents healing and wound closure,” SPERo said, adding that when it is serious, 1 in 5 diabetic foot ulcers require amputation. “It is very impaired, but there is not much microbiology research in this area. So it is an opportunity to make a big difference.”

The displacements in the blood flow, the high demand for the oxygen of inflammatory cells and the presence of bacteria in the position of chronic trauma limit how much oxygen reaches the tissue, preventing healing. These low oxygen conditions are also the very problem that makes bacterial infections difficult to fight: it reveals the resistance and tolerance of antibiotics.

When a trauma position becomes limited by oxygen, the bacteria move to nitrate respiratory for energy, known as nitrate breathing. Their growth slows down without oxygen, but they still survive and continue to spread.

The resulting slow growth of bacteria, especially P. aeruginosa, makes them known to conventional antibiotics. This is due to the fact that many medicines are rated on the basis of how well they kill rapidly growing bacteria, SPERO said. But if the bacteria grow slowly, these antibiotics, which are often examined only in oxygen -rich conditions, end up being ineffective, he said.

At least when they are administered on their own, SPERo found.

To take more miles than current antibiotics

When antibiotics are combined with a small molecule called chlorine salt, “it emphasizes the bacterial cell in a way that makes it extremely sensitive to antibiotics,” Spero said.

The research is based on studies that SPERO is being carried out for the first time as a postdoctoral researcher at the California Institute of Technology. He previously found that the chloric salt, a simple compound that is harmless to mammals and people in the low doses used in its studies, converts antibiotics from lukewarm interpreters into powerful bacterial killers into cellular crops and diabetic models.

Thanks to a $ 1.84 million grant for five years from the National Institutes of Health, SPERO was able to continue its project in its new workshop in the UO. Her latest study shows that chloride works to make antibiotics more effective for killing P. aeruginosa and can reduce the dose of antibiotics required to fight the pathogen. With a small amount of chloride in the mixture, its team could use 1 % of the typical dose of the antibiotic CEFTAZIDIME broad spectrum, according to the study.

“In the case of chronic infections, people are often in antibiotics for long periods and this can cause destruction in the body,” Spero said. “Drugs with high toxicity can disrupt bowel germs and have serious side effects. Anything we can do to reduce the amount of time a person is to be in antibiotic and reduce dosage, the better.”

The results come from controlled laboratory tests in bacterial cell crops, so the translation into the clinic is still well below the line. Especially because chronic infections usually do not include a single bacterium, SPERO said, as they host entire microbial neighborhoods that live and interact together. Thus, revealing the way in which combinations of drugs affect these complex communities in model organisms is an obvious next step, he added.

The exact mechanism for how chlorine salts enhance antibiotics is still a mystery. SPERo explained that the chloric salt is known by scientists to occupy nitrate breathing, so that in complete absence of oxygen, the germs are eliminated. But in low or high or high oxygen base, bacteria can somehow repair that they harm and tolerate the chemical. Thus, in the traditional projections of a drug, which are usually performed in high oxygen conditions, the chloric salt has been overlooked, SPERO said.

“I think this is not fully appreciated: the types of trends imposed by these compounds on the cell that are invisible to us,” he said. “If our only metric is viability – do bacteria live or die?

SPERO hopes that the appearance of a “under the hood” of a cell during chopper-antibiotic exhibitions will show scientists with the biological mechanism of how bacteria become sensitive to a series of antibiotics.

“This will have significant consequences not only for the treatment of chronic wound infections but also for the infectious diseases and the fight against antibiotic resistance and the failure of treatment,” Spero said. “As soon as we understand the mechanisms of the synergy of drugs, we can begin to find other molecules that cause these synergistic behaviors and we will not feel like a game of speculations where we try every possible combination of medicines.