New Drug Combination Offers Hope for Chronic Wound Infections

Researchers at the University of Oregon have made significant strides in combating chronic wound infections through a new combination drug therapy. Their findings, published on September 29, 2023, in the journal Applied and Environmental Microbiology, reveal a promising approach to tackling the persistent bacteria that complicate healing in chronic wounds, particularly those caused by the bacterium Pseudomonas aeruginosa.

Chronic wounds are defined as injuries that fail to heal within the typical timeframe of four to twelve weeks. The most prevalent among these is the diabetic foot ulcer, which often results from poor circulation and prolonged pressure on the foot. According to research from the American Diabetes Association, approximately 25% of individuals with Type 2 diabetes will experience a foot ulcer, with more than half of these cases becoming infected.

Melanie Spero, an assistant professor of biology at the University of Oregon and senior author of the study, emphasized the critical need for advances in this area: “An active infection is the most common complication that prevents the wound from healing and closing.” She noted that in severe cases, up to 20% of diabetic foot ulcers may lead to amputation, underscoring the urgency of effective treatments.

The research, funded by the National Institutes of Health, explores a novel pairing of known substances that individually show limited efficacy against difficult pathogens. By introducing small doses of chlorate alongside standard antibiotics, the combination demonstrated a remarkable increase in effectiveness—up to 10,000 times more potent in laboratory settings than antibiotics used alone.

This discovery not only reduces the necessary dosage of medication required to combat P. aeruginosa but also holds potential for minimizing the duration of antibiotic treatment. Spero explained, “In the case of chronic infections, people are often on antibiotics for long periods of time, and that can wreak havoc on the body.” By shortening treatment duration and lowering dosages, the therapy could mitigate the risk of side effects and toxicity.

The challenge of treating chronic wounds lies in the low-oxygen environment they often present, which promotes antibiotic resistance. In these conditions, bacteria like P. aeruginosa adapt by using nitrate for energy, which slows their growth but allows them to survive. Traditional antibiotics, which are typically evaluated in oxygen-rich environments, fail to effectively target these slow-growing bacteria.

Spero’s previous research at the California Institute of Technology laid the groundwork for this latest study, demonstrating that chlorate can enhance the efficacy of various antibiotics. With a grant of $1.84 million from the National Institutes of Health, she has continued this exploration at the University of Oregon, finding that even a small amount of chlorate allows for significant reductions in antibiotic dosages needed to combat P. aeruginosa.

The implications of this research extend beyond chronic wounds. Spero suggests that the strategy could be instrumental in addressing the broader issue of antibiotic resistance: “Finding examples of synergy among antimicrobials already on the market is going to be really valuable.”

Despite the promising laboratory results, Spero cautions that translating these findings to clinical settings will require further investigation. Chronic infections typically involve complex microbial communities rather than a single bacterium, making it essential to understand how drug combinations interact within these environments.

Understanding the precise mechanism by which chlorate enhances antibiotic efficacy remains an area of active research. Spero noted that chlorate appears to disrupt nitrate respiration in bacteria, leading to increased susceptibility to antibiotics. As researchers look deeper into the biological processes at play, they aim to uncover additional compounds that exhibit similar synergistic effects.

Spero concluded, “This will have important implications not only for treating chronic wound infections but also broadly for the infectious disease field and our fight against antibiotic resistance and treatment failure.” As scientists continue to explore the potential of drug combinations, the hope is to develop more effective treatment protocols that leverage existing medications to improve patient outcomes.