Shifting the Spotlight to the Biofilm Structure: Why Only Targeting the Bacteria in Wounds is Not Enough

The Emerging Science of Biofilm is a new occasional sponsored column from Next Science, Jacksonville, FL. Installments will feature information on the challenges and triumphs of biofilm treatment — what we know and what we hope to learn.

In an era of value-based health care, infections still consume a large portion of our health care dollars. Because of readmissions, progression to higher levels of acuity (ie, amplified morbidity and mortality), unsuccessful use of high-end advanced therapies, or penalties and reduced reimbursement, infections are taking center stage, costing more without reducing their impact. In 2014, hospitals saw their Medicare reimbursement diminish by >1%. equating to more than $373 million in lost revenue due to penalties associated with infections.^1,2 Penalties for infections considered avoidable accounted for 65% of the $26 billion Medicare spends annually on readmissions for infection.² Despite advances in technologies to identify and treat infections, the cost associated with chronic wounds is now >$25 billion annually; wound infection costs are trending upward while treatment reimbursement is trending in the opposite direction.² 

Biofilm is comprised of an organic slime secreted by bacteria trying to build a protective structure against assault from the body’s immune system or from antibiotic/antimicrobial attack. The extracellular polymeric substance (EPS) secreted by the bacteria is initially composed of proteins and smaller molecules strung together to make larger, stronger polymer units of sugars (polysaccharides) with macromolecules such as DNA and lipids. Once present on the wound surface, these previously water-soluble units sequester metallic ions from their surroundings in the form of calcium or iron metallic bonds, which then begin to mediate the cell-to-cell and cell-to-surface interactions of a biofilm. After metallic bonds are established in the substance, it becomes an insoluble capsular environment that evolves through intercellular communication, promoting bacterial growth, mutation, and proliferation. When the metallic bonds are intact, the biofilm improves its impervious position to internal assault or external attack, becoming more robust, developing resistance, and eventually progressing to biofilm proliferation with infectious potential. 

Biofilm in wounds is not a newly recognized problem. The construct known as biofilm has been studied by the scientific community since the early 1990s with limited translation to bedside care. Scientific contributions regarding biofilm and its impact on wound healing have continued to define the influence of bacteria in the wound and delineate the structural components of biofilm. However, until recently these findings have had a singular approach, with wound bacteria the focal point of treatment. Today, science and the validation of randomized controlled trails on the topic continue to emerge, providing wound care professionals glimpses into the mechanisms of biofilm pathophysiology. New evidence is beginning to answer the questions of how bacteria within a biofilm structure impact wound healing and provide ways to recover the healing cascade that can be disrupted by biofilm-mediated processes. Published studies have documented that up to 90% of chronic wounds and 6% of acute wounds are stalled in an inflammatory cycle of biofilm-induced wound degradation and failure to heal. Deploying the gold standard treatment of debridement (where clinically feasible) or utilizing sophisticated topical antimicrobial treatments with custom antibiotic mixtures (driven by specialty microscopy or DNA analysis) are gaining recognition, but such approaches can provide incomplete or ineffectual biofilm therapy. Although debridement can provide a transient reprieve from biofilm in the reduction of bacterial loads and topical treatments have positive effects against bacteria outside of the biofilm (planktonic or free-floating), the impact of these treatment modalities is short-lived because biofilm can recover to maturity in as little as 24 hours.^3,4 

Although studies demonstrate the sophisticated and intricate communication of bacteria within the biofilm (quorum sensing) and how bacteria metamorphosize into an array of bacterial phenotypes or become quiet through quintessence, the consistent factor identified in every biofilm is the structure. Current topical treatment offerings work intermittently at best, with little to no impact on the biofilm structure. As emerging science transitions the focus to biofilm  structure, it is evident that during the evolution of biofilm formation the key structural components are the metallic bonds. Without these bonds, the biofilm is reduced to water-soluble polymers and exposed bacteria are less likely to withstand assaults. With this understanding, treatment choices for biofilm become prioritized based on foundational tenets for success. The optimal biofilm treatment requisites include:

• broad antimicrobial spectrum (biofilm is often polymicrobial, including gram-positive and gram-negative bacteria and fungi);
• a mechanism of action that does not result in the development of microbial resistance;
• high tissue compatibility (one that is noncytotoxic and will not negatively impact healthy cells or healing);
• sustained barrier effect that prevents biofilm re-formation⁵; and
• the ability to dismantle the biofilm EPS structure (ie, the ability to bind the metallic bonds rendering the EPS structurally soluble, bringing it into solution).

The self-perpetuating life-cycle of biofilm and resident pathogens are a recognized and proven barrier to wound healing. Every stage of biofilm development — from surface inoculation, attachment, growth, and regrowth of the protective gel structure — is naturally designed to withstand even the most robust external attack. Using biomechanical science, in vitro and in vivo testing continues to validate that the only effective way to treat persistent biofilm is to dissolve the protective EPS matrix, exposing and killing the bacteria within. 

The success of most antimicrobial and antiseptic products (dressings, gels, or washes) is dependent on direct contact and interaction with the pathogens. Because of the protective biofilm structure, current treatments are limited to attacking unprotected or exposed bacteria, which account for only 10% to 20% of biofilm-based pathogens; these treatments fail to reach 80% to 90% of the bacteria encased within its EPS.⁶  

Absorbing loose bacteria, recently dispersed bacteria, or breaking the biofilm apart with debridement, as demonstrated by a recent Georgetown University study,⁴ only partially addresses biofilm and results in intermittent reductions in pathogenic loads. Evidence now suggests that killing free-floating or planktonic bacteria and breaking apart biofilm may actually enhance the lifecycle, stimulating robust biofilm protection more rapidly, often within minutes to hours. Meeting these key treatment elements should provoke providers to understand the mixed messages of treatments that have had partial effectiveness but failed to recognize the true resilience of the biofilm — that is, its structure. Key to biofilm’s demise is understanding that biofilm is not a specific bacterial type nor related to traditional wound chronicity; instead, it should be viewed as a structure designed to house, protect, and promote its community of inhabitants. 

The Emerging Science of Biofilm is made possible through the support of Next Science, Jacksonville, FL (www.nextscience.com). The opinions and statements of the clinicians providing The Emerging Science of Biofilm are specific to the respective authors and not necessarily those of Next Science; OWM, or HMP. This article was not subject to the Ostomy Wound Management peer-review process.