Impact of Antimicrobial Resistance on wound healing
Introduction
Antimicrobial resistance (AMR) is strengthening its roots in the absence of infection prevention and control measures. The frequent rise in antimicrobial resistance cases, are alarming. A report estimated the drastic rise in AMR associated death by year 2050.
Delayed wound healing and wound infections due to antibiotic resistance can lead to high mortality. For the prevention of chronic wounds and efficient wound healing, it is required to understand factors that affect the overall process. Like the physiological process of normal wound healing, chronic health conditions of an individual, recent exposure to antibiotics, general hygiene etc.
Implications of antimicrobial resistance in the wound healing process.
Skin functions as a crucial barrier to protect us from microbial and environmental infections. Skin possess remarkable ability to heal itself after an injury. A highly choreographed molecular and cellular cascade ensures the body’s barrier against opportunistic pathogens is repaired promptly.
Incase of severe tear to the skin be it accidental or during a surgical procedure, antibiotics are necessary to prevent opportunistic microbial infections at the site of tear.
However, the resistance causing pathogens affect the wound site which prolongs the inflammation phase and delays recovery. This results in increased risk of persistent infection, impaired proliferation and extended time in remodeling.
It is important to understand the stages of wound healing to comprehend the implication of AMR on wound recovery and infections. Wound healing is a structured phenomenon involving following stages:
● Hemostasis- constriction of blood vessels to reduce bleeding
● Inflammation- removal of cellular debris and foreign particles with the help of neutrophils and macrophages to reduce chances of infection
● Proliferation- formation of new cells and tissues, regeneration of the blood supply
● Remodeling- removal of excess cells and complete healing
The potential risk of opportunistic pathogens
Weak immune system or certain chronic health conditions increases the risk of persistent wounds. Certain health conditions like diabetes, chemotherapy, administration of immunosuppressant, HIV are responsible for delaying wound recovery in general. The rise of resistant microbes makes wound healing in people with such pre-existing conditions more complicated. The commonly reported resistant bacteria associated with delayed wound healing, as per this study are:
● Candida albicans,
● Staphylococcus aureus,
● Escherichia coli,
● Proteus species,
● Klebsiella pneumoniae,
● Pseudomonas aeruginosa
● Acinetobacter baumannii.
Hyperglycemia patients are also likely to suffer from and chronic wounds. Leading to prolonged prescription of antibiotics in them and hence an increased risk of the normal microflora of the individual developing resistance to antibiotics . According to latest statistics of WHO, 77 million people in India are suffering from type 2 diabetes, and around 25 million are in pre-diabetic zone.
It is crucial to modify the therapeutic approach and minimize the selection pressure entirely on conventional antibiotics. Rational use of systemic and topical antimicrobials can be an incredible tool to limit and control the use of resistance development.
Innovations in wound healing
A few innovators rooted in deep-tech are using alternate strategies to counter the problem of delayed wound healing.
Start-ups like Koshkey, Macro Biologics, Trellis Bioscience, and Peptilogics are a few that are part of the extended CARBX-GAN and C-CAMP network.
Koshkey Sciences-a C-CAMP supported initiative is harnessing the power of innate immunity. Their innovation invoves developing RNA interference therapies for non-healing diabetic wounds. Koshkey has successfully designed a drug molecule, called antisense oligonucleotides (ASO’s) and small interfering RNA (siRNA) which triggers release of antimicrobial peptides from skin cells. In clinical and preclinical studies, antimicrobial peptides (AMP) show efficient response against antibiotic-resistant strains and potent for treatment of infected chronic diabetic wounds.
The unique advantages of AMP in treatment of skin infections, diabetic wound healing and effectiveness against broad spectrum antibiotics makes it an ideal candidate. Since, AMPs are part of body innate immune response it does not induce any toxicity or undesirable immune response.
Macro Biologics (formerly known as Amicrobe) has been funded by CARB-X to develop a large molecule therapeutic, Amicidin-β. This is designed for direct application to tissues. This molecule has dual properties of a surfactant and microbicidal and thus has potential to make an impact in infections with bio-film formation. Amicidin-β potentially can have application in infections associated with orthopedic implants, general surgeries, trauma cases etc.
Trellis Bioscience and Peptilogics are both focused on infections associated with orthopedic/ joint surgeries. Trellis Bioscience has a monoclonal antibody called TRL1068 designed to clear bio-films associated with bacterial infections. While Peptilogics is developing a unique engineered peptide to treat infections with prosthetic joints. These CARB-X supported innovations are in Phase 1 stage of development.
Futuristic approaches to resolve delayed wound healing
Prevalence of antimicrobial resistance pathogens in management of wounds requires effective and innovative therapeutic approaches. Research and development of systemic, topical and certain preventive measures can help in better management of wound culture, in early stages.
Antibiotic resistance breakers (ARBs), nanotherapy, immunotherapy, phage therapy are promising range of solutions to mitigate the concerns of AMR. These solutions when combined with innovations in bioengineered skin grafts, and 3D bioprinting will ensure their optimal impact.
Implementing a combination of these approaches, tailored to specific contexts and infections is crucial in development of comprehensive strategy against resistant bacterial strains.
Conclusion
The escalating threat of antimicrobial resistance poses formidable challenges to wound healing. As bacteria continue to evolve and develop resistance to conventional antibiotics, the intricate stages of healing is witnessing disruptions leading to increased infection risks. The repercussions especially in immunocompromised individuals and individuals with life-style diseases are grave. Considering the high prevalence of diabetes and cardiovascular diseases in Indian population, dedicated efforts must be directed towards understanding the nexus of wound healing, resistant bacteria, and common co-morbidities observed in India.
It calls for combined efforts to foster global collaboration and invest in alternative strategies while also, promoting responsible and prescribed use of antibiotics. Only through innovation, invention and awareness that ensures next generation technologies are coupled with basics of antibiotic stewardship, challenges associated with antimicrobial resistance can be navigated.
References
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524042/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163183/
https://www.sciencedirect.com/science/article/pii/S1319562X22000158#ab005
