Clinical management of chronic wound infections: The battle against biofilm.

Bacteria constitute the most abundant life form on earth, of which the majority exist in a protective biofilm state. Since the 1980s, we have learned much about the role of biofilm in human chronic infections, with associated global healthcare costs recently estimated at ~$386 billion. Chronic wound infection is a prominent biofilm-induced condition that is characterised by persistent inflammation and associated host tissue destruction, and clinical signs that are distinct from signs of acute wound infection.

Early clinical performance of an adaptive self-assembling barrier scaffold in nonhealing chronic wounds: a review of six cases.

Introduction: Chronic nonhealing wounds pose a serious concern for patient health and the health care system. Management of chronic wounds becomes especially challenging in the setting of systemic comorbidities and patient nonadherence.

Objective: Authors evaluated the performance of a proprietary adaptive self-assembling barrier scaffold (aSABS) in the management and healing of complex chronic wounds.

Urethral Catheter Biofilms Reveal Plasticity in Bacterial Composition and Metabolism and Withstand Host Immune Defenses in Hypoxic Environment.

Biofilms composed of multiple microorganisms colonize the surfaces of indwelling urethral catheters that are used serially by neurogenic bladder patients and cause chronic infections. Well-adapted pathogens in this niche are , and spp., species that cycle through adhesion and multilayered cell growth, trigger host immune responses, are starved off nutrients, and then disperse.

Biofilm and catheter-related bloodstream infections.

Careful attention to detail and adherence to procedure guidelines when inserting and managing intravascular catheters has decreased the incidence of catheter-related bloodstream infections (CRBSIs). In order to limit these, health professionals must understand the underlying microbiology. Biofilms can explain the clinical findings most often seen with CRBSIs, yet they are poorly understood within medicine.

Biofilm exacerbates antibiotic resistance: Is this a current oversight in antimicrobial stewardship?

Objective: To raise awareness of the role of environmental biofilm in the emergence and spread of antibiotic resistance and its consideration in antimicrobial stewardship.

Background: Antibiotic resistance is a major threat to public health. Overuse of antibiotics, increased international travel, and genetic promiscuity amongst bacteria have contributed to antibiotic resistance, and global containment efforts have so far met with limited success.

A review of iodine-based compounds, with a focus on biofilms: results of an expert panel.

Biofilms play a central role in the chronicity of non-healing lesions such as venous leg ulcers and diabetic foot ulcers. Therefore, biofilm management and treatment is now considered an essential part of wound care. Many antimicrobial treatments, whether topical or systemic, have been shown to have limited efficacy in the treatment of biofilm phenotypes.

Patient genetics is linked to chronic wound microbiome composition and healing.

The clinical importance of microbiomes to the chronicity of wounds is widely appreciated, yet little is understood about patient-specific processes shaping wound microbiome composition. Here, a two-cohort microbiome-genome wide association study is presented through which patient genomic loci associated with chronic wound microbiome diversity were identified. Further investigation revealed that alternative TLN2 and ZNF521 genotypes explained significant inter-patient variation in relative abundance of two key pathogens, Pseudomonas aeruginosa and Staphylococcus epidermidis.

Chronic wound microbiome colonization on mouse model following cryogenic preservation.

Chronic wound infections are increasingly recognized to be dynamic and polymicrobial in nature, necessitating the development of wound models which reflect the complexities of infection in a non-healing wound. Wound slough isolated from human chronic wounds and transferred to mice was recently shown to create polymicrobial infection in mice, and there is potential this tool may be improved by cryogenic preservation. The purpose of this study was to investigate the application of cryogenic preservation to transferring polymicrobial communities, specifically by quantifying the effects of cryopreservation and wound microbiome transplantation.

Bacterial fitness in chronic wounds appears to be mediated by the capacity for high-density growth, not virulence or biofilm functions.

While much is known about acute infection pathogenesis, the understanding of chronic infections has lagged. Here we sought to identify the genes and functions that mediate fitness of the pathogen Pseudomonas aeruginosa in chronic wound infections, and to better understand the selective environment in wounds. We found that clinical isolates from chronic human wounds were frequently defective in virulence functions and biofilm formation, and that many virulence and biofilm formation genes were not required for bacterial fitness in experimental mouse wounds.

Improving the quality of clinical research on chronic wound infection treatment: expert-based recommendations.

Objective:: To produce recommendations for the design of reliable and informative clinical investigations in chronic wound infection.

Method:: A multidisciplinary panel of international experts from four countries (Italy, UK, Ireland and the US) were involved in a detailed, semi-structured discussion on how to better select and describe a target population, interventions and outcomes, and which infection-related criteria to apply in order to achieve a high-quality trial. Consent among the experts was measured using the Delphi method and GRADE Working Group suggestions.

transcriptome during human infection.

Laboratory experiments have uncovered many basic aspects of bacterial physiology and behavior. After the past century of mostly in vitro experiments, we now have detailed knowledge of bacterial behavior in standard laboratory conditions, but only a superficial understanding of bacterial functions and behaviors during human infection. It is well-known that the growth and behavior of bacteria are largely dictated by their environment, but how bacterial physiology differs in laboratory models compared with human infections is not known.

Efficacy of hyperbaric oxygen therapy in bacterial biofilm eradication.

Objective: Chronic wounds typically require several concurrent therapies, such as debridement, pressure offloading, and systemic and/or topical antibiotics. The aim of this study was to examine the efficacy of hyperbaric oxygen therapy (HBOT) towards reducing or eliminating bacterial biofilms in vitro and in vivo.

Method: Efficacy was determined using in vitro grown biofilms subjected directly to HBOT for 30, 60 and 90 minutes, followed by cell viability determination using propidium monoazide-polymerase chain reaction (PMA-PCR).

Understanding biofilm in practice: a global survey of health professionals.

Objective: The aim of this survey was to examine health professionals' views and practices relating to biofilm in chronic wounds.

Method: A global online survey was conducted to assess the current understanding of biofilm and wound management practices. The survey consisted of 20 questions designed to evaluate health professional knowledge of biofilm, perception and understanding of biofilm behaviour, detection and diagnosis, and treatment.

Temporal dynamics of relative abundances and bacterial succession in chronic wound communities.

Polymicrobial bacterial infection is an important factor contributing to wound chronicity. Consequently, clinicians frequently adopt a biofilm-based wound care approach, in which wounds are treated utilizing DNA sequencing information about microbial communities. While more successful than treatment not using community information, there is little information about temporal dynamics of wound communities and optimal approaches over the course of treatment.

A post-planktonic era of in vitro infectious models: issues and changes addressed by a clinically relevant wound like media.

Medical science is pitted against an ever-increasing rise in antibiotic tolerant microorganisms. Concurrently, during the past decade, biofilms have garnered much attention within research and clinical practice. Although the significance of clinical biofilms is becoming very apparent, current methods for diagnostics and direction of therapy plans in many hospitals do not reflect this knowledge; with many of the present tools proving to be inadequate for accurately mimicking the biofilm phenomenon.

Microbiota is a primary cause of pathogenesis of chronic wounds.

Objective: Diverse microorganisms present on the surface of chronic wounds have been established to constitute wound microbiota. The aims of this study were to quantify the viability of wound microbiota, classify dispersal of viable microbes from the wound, and determine if human wound microbiota can produce a chronic wound in an animal model.

Method: Wound microbiotas as units (multiple microbial species acting as one infectious agent) were obtained from well-defined human chronic wounds and seeded onto mouse surgical excision wounds to produce chronically infected wounds that closely resembled the chronic wounds observed in the original hosts.

Recommendations for the management of biofilm: a consensus document.

The potential impact of biofilm on healing in acute and chronic wounds is one of the most controversial current issues in wound care. A significant amount of laboratory-based research has been carried out on this topic, however, in 2013 the European Wound Management Association (EWMA) pointed out the lack of guidance for managing biofilms in clinical practice and solicited the need for guidelines and further clinical research. In response to this challenge, the Italian Nursing Wound Healing Society (AISLeC) initiated a project which aimed to achieve consensus among a multidisciplinary and multiprofessional international panel of experts to identify what could be considered part of 'good clinical practice' with respect to the recognition and management of biofilms in acute and chronic wounds.

The presence of biofilm structures in atherosclerotic plaques of arteries from legs amputated as a complication of diabetic foot ulcers.

Objective: Atherosclerosis, rather than microcirculatory impairment caused by endothelial cell dysfunction, is the main driver of circulatory compromise in patients with diabetic limbs. The presence of atherosclerotic plaque at the trifurcation is a significant contributor to amputation of diabetic legs. The presence of bacteria and other microorganisms in atherosclerotic plaque has long been known, however, the cause of chronic inflammation and the role of bacteria/viruses in atherosclerosis have not been studied in detail.

Disrupting the biofilm matrix improves wound healing outcomes.

Objective: The most unyielding molecular component of biofilm communities is the matrix structure that it can create around the individual microbes that constitute the biofilm. The type of polymeric substances (polymeric sugars, bacterial proteins, bacterial DNA and even co-opted host substances) are dependent on the microbial species present within the biofilm. The extracellular polymeric substances that make up the matrix give the wound biofilm incredible colony defences against host immunity, host healing and wound care treatments.

Analysis of the chronic wound microbiota of 2,963 patients by 16S rDNA pyrosequencing.

The extent to which microorganisms impair wound healing is an ongoing controversy in the management of chronic wounds. Because the high diversity and extreme variability of the microbiota between individual chronic wounds lead to inconsistent findings in small cohort studies, evaluation of a large number of chronic wounds using identical sequencing and bioinformatics methods is necessary for clinicians to be able to select appropriate empiric therapies. In this study, we utilized 16S rDNA pyrosequencing to analyze the composition of the bacterial communities present in samples obtained from patients with chronic diabetic foot ulcers (N = 910), venous leg ulcers (N = 916), decubitus ulcers (N = 767), and nonhealing surgical wounds (N = 370).