Infected Wounds

Centuries ago, science took a back seat to superstition. Infectious diseases were seen as a sign of supernatural powers or the wrath of God. We now know that it was smallpox that led to the downfall of the Aztecs. We also know that bubonic plague was not a divine punishment, but it was caused by bacteria transmitted by fleas on rodents traveling on trading ships.

Wounds typically heal in four sequential but overlapping phases — hemostasis, inflammatory, proliferative and remodeling — ultimately leading to tissue regeneration. Healing sometimes stalls for various reasons, a key one being extensive inflammation, which disrupts the normal cascade of healing and leads to chronic and hard-to-heal wounds. A vicious cycle of ongoing inflammation, pain and poor quality of life often follows. Understanding how to break this cycle is essential for wound care clinicians who want to optimize healing outcomes and patient quality of life.

Wound healing can stall for a number of reasons. Wounds that have not healed or significantly reduced in size after four to six weeks are considered chronic. They are characterized by a multitude of impeding factors including biofilm, excess matrix metalloproteinases (MMPs) and extracellular matrix degradation, inflammation, fibrosis, unresponsive keratinocytes and fibroblasts, and atypical growth factor signaling.

Biofilm: Colonies of multiphenotype, free-floating bacteria that secrete a polysaccharide matrix that protects the bacteria from immune response and antibiotics.

Chronic wounds: Wounds that stall in the inflammation phase and fail to progress toward healing within 3 months are considered chronic or hard to heal.

Continuous inflammation: When wound healing becomes stalled in the inflammatory phase because of the presence of bacteria and their endotoxins, the wound is unable to move out of the inflammatory phase and into the repair phase.

As scientists and researchers have delved deeper into the causes of wounds and wound chronicity, matrix metalloproteinases, or MMPs, have come into sharper focus. MMPs are not just present in chronic wounds — they also play an essential role in acute wounds.

An injury to the human body initiates a wound healing chain reaction that occurs in four sequential but overlapping phases: hemostasis, inflammatory, proliferative and maturation. This post focuses on the second (inflammatory) phase, which begins after blood flow stops (i.e., hemostasis) and defender white blood cells, or leukocytes, migrate to the site of the injury — a process known as chemotaxis.

The outer layer of the skin, the epidermis, is the body's physical barrier to the environment. This barrier is compromised when moisture or trauma damages the epidermis. Frequently, moisture or adhesives can damage the skin and cause painful injuries. The damaged area is then more susceptible to infection and delayed healing.

Overexposure to moisture can compromise the skin's integrity by disrupting the delicate molecular arrangement of intercellular lipids in the stratum corneum and the intercellular connections between epidermal cells or corneocytes. The term moisture-associated skin damage (MASD) encompasses a spectrum of injuries characterized by denudation (inflammation and erosion) of the epidermis resulting from prolonged exposure to various sources of moisture or irritants such as wound exudate, perspiration, urine, stool, or ostomy effluent.

Antibiotic resistance is a growing health threat, not just in the United States, but throughout the world. Health care professionals are facing problems with antibiotic resistance, as well as with resistance to other antimicrobial agents. The Centers for Disease Control and Prevention (CDC) noted in 2019 that “more than 2.8 million antibiotic-resistant infections occur in the United States (US) each year, and more than 35,000 people die as a result.” The CDC lists 18 current threats, with three on the watch list as emerging causes of antibiotic resistance. Many of the bacteria on this threat list are found in chronically stalled wounds. Therefore, wound clinicians must be good stewards of antimicrobial treatments to prevent contributing to an already worsening problem.

Treatment of chronic and complex wounds complicated by biofilm formed by pathogens remains a tremendous challenge for the health care industry. Recent increases in infections mediated by drug-resistant bacterial and fungal pathogens highlight the need for new antimicrobial therapies. The application of topical agents with antimicrobial and antiseptic properties is gaining traction as an alternative to antibiotic prescriptions.

Antibiosis: The biological relationship between two organisms in which one living organism kills another to ensure its existence.

Antimicrobial resistance: The process that occurs when bacteria, fungi, and parasites (microorganisms) change over time and no longer respond to antimicrobial medications. This resistance makes it more difficult to treat infections and increases the risk of spreading diseases that result in severe illness and death.

Antimicrobial stewardship plan: An antimicrobial stewardship plan should seek to prevent wound infection in the first place and should promote ideal antibiotic use in clinically infected patients while also preventing use of antibiotics in non-infected patients.