New Drug Combo Targeting Chronic Wound Infections Shows Promise

Researchers at the University of Oregon have developed a promising new combination drug therapy that significantly enhances the treatment of chronic wound infections. Their findings, published on September 29, 2023, in the journal Applied and Environmental Microbiology, suggest that this approach could effectively tackle the bacterial strains that complicate healing in chronic wounds, particularly those associated with diabetes.

The study focused on the notorious bacterium Pseudomonas aeruginosa, which is frequently implicated in chronic wound infections. By combining traditional antibiotics with small doses of a molecule known as chlorate, the researchers achieved a remarkable increase in effectiveness—up to 10,000 times more effective in laboratory settings compared to single-drug treatments. This breakthrough not only reduces the required dosage of antibiotics but also has the potential to shorten the duration of treatment, thereby minimizing the risks of toxicity for patients.

Chronic wounds, particularly diabetic foot ulcers, pose a significant health challenge. According to research from the American Diabetes Association, approximately 25% of individuals with Type 2 diabetes will develop a foot ulcer, and more than half of these cases become infected. As Melanie Spero, an assistant professor of biology at the University of Oregon and senior author of the study, explains, “An active infection is the most common complication that prevents the wound from healing and closing.” In severe cases, 20% of diabetic foot ulcers may necessitate amputation.

The chronicity of these wounds can be attributed to several factors, including inadequate blood flow and the presence of bacteria that thrive in low-oxygen environments. These conditions activate antibiotic resistance mechanisms, making standard treatments ineffective. Spero notes, “When a wound site becomes oxygen-limited, bacteria switch to breathing nitrate for energy, known as nitrate respiration,” which allows them to survive despite antibiotic treatment.

The introduction of chlorate into the treatment regimen alters the dynamics of bacterial survival. Spero’s previous research at the California Institute of Technology revealed that chlorate, at low doses, enhances the potency of antibiotics, transforming them from mediocre to highly effective agents against P. aeruginosa. With support from a $1.84 million grant from the National Institutes of Health, Spero has expanded her investigations into this area at her current laboratory.

In lab tests, the combination of chlorate and antibiotics allowed for the use of just 1% of the standard dose of the broad-spectrum antibiotic ceftazidime while maintaining efficacy against the bacteria. Spero emphasized the importance of reducing the duration of antibiotic treatment: “People are often on antibiotics for long periods of time, and that can wreak havoc on the body.” Shortening treatment could mitigate severe side effects and help preserve gut microflora.

While the findings are promising, Spero cautioned that these results stem from controlled laboratory settings. Chronic infections often involve complex microbial communities, and the next phase of research will investigate how these drug combinations function within those environments. Understanding the mechanisms underlying chlorate’s enhancement of antibiotic efficacy remains a critical area for further exploration.

Spero concluded, “Once we understand the mechanisms of drug synergy, we can start to find other molecules that elicit these synergistic behaviors.” This research not only has the potential to improve treatments for chronic wound infections but could also contribute significantly to the broader fight against antibiotic resistance, a growing concern in the medical community.

As research progresses, the hope is that this innovative approach will lead to more effective strategies in managing infections that threaten the health and mobility of many patients worldwide.