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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.

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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.

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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.

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Antibiotic resistance is considered a significant public health concern by multiple international organizations. The US Centers for Disease Control and Prevention estimate that approximately 35,000 deaths occur in the United States each year related to antibiotic resistance. Moreover, the agency predicts that millions more deaths will occur in the coming decades. By 2050, it is estimated that the number of deaths resulting from drug-resistant infections will surpass 10 million, which equates to one person dying every three seconds. The total global cost to economic output related to these deaths is estimated at US $100 trillion.

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Wound healing is often accompanied by bacterial infection. Many clinicians use antibiotics to treat wound infections. However, the overreliance on antibiotics is becoming an increasing concern for many global health organizations because it contributes to widespread antibiotic resistance. Excessive use of synthetic antibiotics leads to drug resistance, which poses a substantial threat to human health.

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Chronic wounds of the lower extremities impose an increasing burden on health care providers and systems, and they can have a devastating impact on patients and their families. These wounds include diabetic ulcers, venous ulcers, arterial ulcers, and pressure injuries. The estimated socioeconomic cost of chronic wounds is 2% to 4% of the health budget in Western countries. Moreover, patient mortality in individuals with chronic wounds has been estimated at 28% over a two-year period, significantly higher than the 4% mortality rate reported for 75 to 79 year-olds without chronic wounds.

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Chronic and non-healing wounds are those that do not progress through the healing process in a timely or predicted manner. They are a global problem and are becoming harder to treat. Medicare estimates that over 8 million Americans have chronic wounds that cost the national health care system between $18.1 and $96.8 billion dollars annually.

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Chronic and complex wounds of the lower extremity frequently recur. It is difficult to determine the precise recurrence rate across patients with different lower extremity wound types, including diabetic foot ulcers, arterial ulcers, pressure injuries, and venous ulcers. However, we know that recurrence rates are high; nearly 40% of patients with an ulcer will develop a recurrence within one year of healing. This percentage is 60% at three years after healing and 65% at the five-year mark.

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Growth factors and cytokines are secreted by the cells and are essential to the complex wound healing and tissue regeneration process. This process involves the interplay of growth factors with chemokines, cytokines, and other signaling molecules. Although there have been numerous advances that have increased our understanding of wound healing, the exact tissue regeneration mechanisms following an injury have yet to be determined.

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Angiogenesis: The complex process in which the growth of normal, stable, and functional vessels is critically dependent on the coordinated interplay in space and time of different cell types and growth factors. This process involves the forming of new blood vessels from preexisting vessels by invading the wound clot to organize in a microvascular network throughout granulation tissue.

Autologous cell therapy: A therapeutic intervention that uses an individual’s cells, which are cultured and expanded outside of the body and reintroduced into the donor as a bioengineered skin substitute to aid in wound closure.

Immunomodulation: Therapeutic interventions aimed at modifying the immune response. Healing in chronic and complex wounds can be enhanced with immunomodulating agents.

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