Despite advances in wound care, bacterial and fungal infections remain among the most common and painful conditions, often leading to significant death and illness. Currently, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa are the most common bacteria found in infected wounds.

Stages of the healing process

The healing process is a meticulously coordinated series of events that involve both resident and migrating cell populations, extracellular matrix components, and soluble mediators. This intricate process can be divided into five distinct phases.

Haemostasis is the initial phase, during which a fibrin clot forms to prevent blood loss through vasoconstriction and to protect against microbial contamination. Simultaneously, the inflammatory phase begins, marked by the recruitment of neutrophils, monocytes/macrophages, and lymphocytes. Neutrophils engulf bacteria, cleanse the wound through proteases and antimicrobial peptide secretion, and produce reactive oxygen intermediates.

Monocytes differentiate into macrophages, facilitating the removal of apoptotic neutrophils and other cells, while also secreting cytokines and growth factors. Lymphocytes contribute with specific responses to combat microbes; B-lymphocytes produce antibodies, and T-lymphocytes secrete cytokines involved in cytolytic activity.

The migration and proliferative phases follow, as fibroblasts migrate to the wound site and differentiate into myofibroblasts, producing extracellular matrix components like fibronectin, hyaluronic acid, collagen, and proteoglycans. These components are integral to extracellular matrix production, the formation of new blood vessels, and re-epithelisation.

The final stage, called maturation or remodelling, marks the conclusion of the wound healing process, in which all processes activated after the injury come to a halt.

Advanced wound dressings

Conventional wound dressings are passive barriers that protect wounds from infection and contamination. Advanced wound dressings, on the other hand, are active participants in the healing process, delivering therapeutic compounds to the wound site. These compounds can aid in the removal of dead tissue, promote tissue growth, and prevent or treat infections.

Antimicrobial dressings are a particularly valuable tool for managing local infections. They deliver high concentrations of antibiotics directly to the wound site, where they can effectively kill bacteria and prevent the development of biofilms. For example:

• Gentamicin-impregnated dressings can be used to treat diabetic foot ulcers.
• Silver sulfadiazine dressings are useful for treating burn wounds.
• In the treatment of chronic wounds that have been colonised by bacteria and biofilms, cadexomer iodine dressings have demonstrated efficacy.

Commonly used antibiotics
Antimicrobial dressings utilise a limited range of antibiotic classes, including aminoglycosides, beta-lactams, glycopeptides, quinolones, sulphonamides, and tetracyclines, each employing diverse mechanisms to disrupt vital bacterial processes.

• Beta-lactams and glycopeptides target bacterial cell wall synthesis.
• Penicillins, carbapenems, and cephalosporins, known as beta-lactam antibiotics, block penicillin-binding proteins, crucial for cell wall construction.
• Glycopeptide antibiotics like vancomycin hinder peptidoglycan synthesis by binding to peptidoglycan within the cell wall, restraining transglycosylases and PBPs. This compromises cell wall integrity and may lead to cell lysis.
• Sulphonamides focus on the bacterial folate pathway essential for growth. Acting as folic acid mimics, they competitively bind to bacterial enzymes, disrupting DNA, RNA, and protein synthesis.
• Aminoglycosides and tetracyclines act as protein synthesis inhibitors by binding to the 30S ribosomal subunit, obstructing aminoacyl-tRNA recruitment to the ribosome and hindering new protein production.
• Quinolones inhibit nucleic acid synthesis by targeting topoisomerase II and topoisomerase IV, enzymes vital for DNA topology maintenance. Quinolones transform topoisomerases into chromosome-fragmenting enzymes, leading to bacterial cell death.

Antimicrobial resistance

Drug-resistant wound infections are a growing threat to wound healing. The primary factor contributing to the emergence of antimicrobial resistance is the inappropriate use of antimicrobial agents, raising concerns about the proliferation of superbugs or multi-drug resistant strains.

Notably, about half of infections associated with bacteria such as Escherichia coli, Klebsiella pneumoniae, S. aureus, and P. aeruginosa have exhibited resistance even to potent antimicrobials like third generation cephalosporins. A fundamental prerequisite for the judicious prescription of antimicrobials is a comprehensive understanding of the criteria for wound infections, the causative pathogens, and their prevalent susceptibility patterns.

Given the established efficacy of wound debridement and irrigation, the initial approach to managing infected wounds should generally not involve prescribing antibiotics. Systemic antibiotics are warranted when the infection appears to be spreading through subcutaneous soft tissues, in cases of ascending limb infection, or when severe sepsis is a concern.

To minimise the impact of individual antibiotics on the normal flora of the skin and gut, preference should be given to narrow-spectrum agents. Empirical treatment with systemic antibiotics should be adapted based on wound culture results, and topical antibiotics have proven effective in managing patients with infected wounds.

REFERENCES

Negut I, et al. Treatment Strategies for Infected Wounds. Molecules, 2018.
Filius PM, et al. Impact of increasing antimicrobial resistance on wound management. Am J Clin Dermatol, 2002;3(1):1-7.
Simões D et al. Recent advances on antimicrobial wound dressing: A review. Eur J Pharm Biopharm, 2018.