Microbiology of Wounds PDF

lPreface

Chronic wounds are a serious public health issue. The incidence and prevalence of the different types of chronic wounds are largely unknown worldwide, but 13 years ago George1 estimated the worldwide burden of wounds to be:

• Surgical wounds, 40 to 50 million

• Leg ulcers, 8 to 10 million

• Pressure ulcers, 7 to 8 million

• Burns, 7 to 10 million

In the United States alone, the estimated number of chronic wounds includes 1 to 2 million diabetic foot ulcers, 1 to 2 million venous leg ulcers, 3 to 5 million pressure ulcers, and 1% surgical site infections. One of the underlying pathologies known to increase the prevalence of chronic wounds is diabetes mellitus. Diabetes mellitus in the Western world is growing continuously at a double-digit rate. However, this figure is not truly representative of the extent of the problem. Figures from the Centers for Disease Control and Prevention (CDC) state that there are approximately 24 million patients with diabetes mellitus (24 million diabetics). Cutaneous wounds in the United States alone cost society over $25 billion annually.

The management of infected wounds remains an area of confusion and hence great debate. No definition or authoritative clinical guidelines of what constitutes an infected wound exists. Terminology in wound care such as colonization, critical colonization, biofilm, and other descriptions of bacterial behavior on the surface of the wound are not clearly defined. Even the term infection requires redefining in light of recently generated insight into the prevalence and behavior of the biofilm phenotype. In addition, many of the concepts concerning wound infections are not backed up with meaningful scientific support. Consequently many terms used in wound care have led to confusion and unnecessary or inappropriate management of chronic wounds.

It is well established that wound healing is dynamic, infinitely complex, nonlinear, and prodigiously individualized to the context of the patient. Understanding the intricacies of chronic wounds becomes even more complex when one considers the myriad of host variables that contribute to the disease state.

The plausible common barrier that may impair many of these wounds from healing is chronic infection as a result of biofilm infection. Chronic biofilm-based infections constitute 80% of all human infection. Accordingly, acute infections remain as the minority census of all infectious disease. The definition of acute infection is based on clinical characteristics of rapid onset and aggressive bacterial behavior, which responds rapidly and completely to antibiotics or the host immune response. Chronic infections are persistent and recalcitrant. It is interesting to note that acute and chronic infections have not been clearly differentiated on a molecular level and may be explained by bacteria pursuing widely divergent survival strategies only now becoming elucidated through research.

Bacteria producing chronic infections employ a biofilm phenotype for their infectious strategy. In this type of survival strategy, the bacteria attach to the host and subvert a number of host systems. First, the bacterium rapidly encases itself inside an extracellular polymeric substance (EPS), which protects the biofilm members from the host's immunity. Bacteria within the biofilm secrete communication molecules termed quorum-sensing molecules, which direct the activity of many bacteria within the community. Subsequently, the bacteria are collectively under partial regulatory control by the community. This highly organized and competent communal structure is biofilm.

This biofilm, now attached and centrally regulated, strives to reproduce itself and obtain sustainable nutrition from host sources. Through multiple modes, the biofilm exploits host inflammatory pathways. By commandeering other host pathways, the biofilm is able to prevent apoptosis in the cells that constitute the wound bed. Consequently, a senescent wound bed is created which may provide a stable base of attachment. Further, the biofilm prevents host neutrophils from lysing the surface of the wound bed to remove the attached biofilm. The biofilm also downregulates bacterial protease activity, and alternatively, stimulates the host inflammatory response to produce increased host protease activity, thereby generating plasma transudate as a constant source of fluid and nutrition for the biofilm community. As previously stated, through quorum sensing the biofilm can regulate the size and activity of the entire community in its pursuit of a parasitic strategy.

The issue of addressing whether or not chronic wounds are "infected" is controversial, and that controversy seems to rely on the traditional diagnostic markers of infection (acute or chronic). Chronic wounds exhibit high proinflammatory cytokines, high host protease activity, and excessive neutrophil infiltration, which is predictably typified by most other tissues affected by the persistent biofilm infection. Also, the secondary signs of infection most common in wounds—such as excessive exudate, a soft degraded and senescent wound bed that fails to progress—are all consistent with a host response to a biofilm.

Acknowledgment of the presence of chronic infection and biofilm in most chronic wounds as an important barrier to healing allows a single, unified perspective for the approach and treatment of chronic cutaneous wounds. Indubitably, patient comorbidities such as neuropathy, immobility, poor perfusion, impaired immunity, malnutrition, and systemic diseases must be aggressively managed as a parallel strategy to optimize the treatment regimen, but if we ignore the contribution of biofilms to infection and fail to manage appropriately, then our care will be suboptimal.