Neem Biotech, a South Wales based R&D pharmaceutical biotech working in the field of novel antimicrobial drug development, and the Welsh Wound Innovation Centre recently attended the Royal College of Physicians’ Innovation in Medicine Conference 2018 where Neem presented their data around wound-relevant biofilms.
The promising laboratory data presented reinforces the role of quorum sensing inhibition in virulence factor regulation and biofilm disruption, with implications for management of antimicrobial resistance.
Dr Graham Dixon, Neem’s CEO and Prof Keith Harding … read more
Identifying and managing biofilms have become two of the most important aspects of wound care. Biofilms can have a significant impact on wound healing, by contributing to bacterial infection, inflammation, and delayed wound healing. These issues make reducing biofilm presence a critical component of effective wound care. Although over 60% of chronic wounds contain a biofilm, many health care professionals are not able to identify biofilm formation in their patients. To manage this challenge effectively, health care professionals must understand what biofilms are, how to identify them, and how to take steps to reduce their impact on wound healing … read more
TEMPE, Ariz., Dec. 5, 2017 /PRNewswire/ — Vomaris Innovations, Inc. announced today breakthrough results of the first controlled, preclinical in vivo evidence on the anti-biofilm impact of the Company’s bioelectric antimicrobial technology. The study found that the technology can prevent and disrupt biofilm infection and restore functional wound healing. The manuscript, “Electric Field Based Dressing Disrupts Mixed-Species Bacterial Biofilm Infection and Restores Functional Wound Healing,” was published online in the Annals of Surgery. The research was led by Chandan Sen, Ph.D., Professor of Surgery and Director of the Comprehensive Wound Center at The Ohio State University’s Wexner Medical Center.
Bacteria use electrical interactions to communicate with each other in a process called quorum sensing (QS), signaling them to adhere to a wound, multiply, and encase themselves within a protective structural substance known as a biofilm. This protective biofilm barrier impedes the body’s immune defense system and renders the bacteria highly resistant to antibiotics, making biofilm infections extremely difficult to treat.
Approximately 80% of infections in chronic and surgical wounds are thought to be caused by bacteria within biofilm.1,2Chronic wounds affect an estimated 6.5 million patients a year and over $25 billion is estimated to be spent annually on their treatment.3 Surgical site infections (SSIs) occur in 2% to 5% of all patients undergoing inpatient surgery and affect up to 300,000 patients a year in the U.S. alone. Annual costs of managing SSIs range from $3.5 billion to $10 billion … full press release
These complex 3D structures of bacteria explain many of the challenges clinicians face with wound care, infection and healing. Scientists are fighting back.
Antonie van Leeuwenhoek (1632-1723) was the first person to delve into the field of microbiology and document initial observations of bacteria. After this preliminary discovery, microbiology was not actively studied again until the 1800s, when it began to gain a foothold in contemporary medicine. Fast-forward to today’s labs, where clinicians are becoming more knowledgeable in the bacteriology of wound healing, and researchers are identifying new ways to overcome long-standing challenges in wound healing, such as biofilms.
Biofilm is a term used to describe a colony of microorganisms, such as bacteria, fungi or yeast, encased by an extracellular polymeric substance (EPS). The EPS forms a shield, often causing the bacteria to be … read more
Researchers from the Ohio State University Wexner Medical Center have developed special electrically charged bandages that can prevent infections, combat antibiotic resistance and enable healing in burn wounds. This type of dressing turns electrically active when it comes in contact with bodily fluids. According to Dr. Chandan Sen, director of Ohio State’s Center for Regenerative Medicine and Cell Based Therapies, who led the study with colleagues at the Medical Center’s Comprehensive Wound Center and Center for Microbial Interface Technology, “Drug resistance in bacteria is a major threat, and antibiotic-resistant biofilm infections are estimated to account for at least 75 percent of bacterial infections in the United States. This is the first pre-clinical long-term porcine study to recognize the potential of ‘electroceuticals’ as an effective platform technology to combat wound biofilm infection.”
Interplay of host antimicrobial peptides and antibiotics
Purpose: The aim of this study is to improve the anti-biofilm activity of antibiotics. We hypothesized that the antimicrobial peptide (AMP) complex of the host’s immune system can be used for this purpose and examined the assumption on model biofilms.
Methods: FLIP7, the AMP complex of the blowfly Calliphora vicina containing a combination of defensins, cecropins, diptericins and proline-rich peptides was isolated from the hemolymph of bacteria-challenged maggots. The complex interaction with antibiotics of various classes was studied in biofilm and planktonic cultures of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii by the checkerboard method using trimethyl tetrazolium chloride cell viability and crystal violet biofilm eradication assays supplemented with microscopic analysis.
Results: We found that FLIP7 demonstrated: high synergy (fractional inhibitory concentration index <0.25) with meropenem, amikacin, kanamycin, ampicillin, vancomycin and cefotaxime; synergy with clindamycin, erythromycin and chloramphenicol; additive interaction with oxacillin, tetracycline, ciprofloxacin and gentamicin; and no interaction with polymyxin B. The interaction in planktonic cell models was significantly weaker than in biofilms of the same strains. The analysis of the dose–effect curves pointed to persister cells as a likely target of FLIP7 synergistic effect. The biofilm eradication assay showed that the effect also caused total destruction of S. aureus and E. coli biofilm materials. The effect allowed reducing the effective anti-biofilm concentration of the antibiotic to a level well below the one clinically achievable (2–3 orders of magnitude in the case of meropenem, ampicillin, cefotaxime and oxacillin).
Led by scientists at UCLA, an international team of researchers has discovered that bacteria have a “memory” that passes sensory knowledge from one generation of cells to the next, all without a central nervous system or any neurons.
“This is a huge surprise to us and to the field,” said Gerard Wong, a professor of bioengineering and of chemistry and biochemistry, member of the California NanoSystems Institute at UCLA and one of the study’s senior authors.
These findings are a major step toward understanding hard-to-treat infections caused by bacterial biofilms in people with cystic fibrosis.
The team studied a strain of bacteria called Pseudomonas aeruginosa that forms biofilms in the airways of people with cystic fibrosis and causes persistent infections that can be lethal. Bacterial biofilms can also form on surgical implants, like an artificial hip; when they do, they can cause the implant to fail. Bacterial biofilms are composed of genetically identical bacteria cells that can colonize nearly any surface and form communities in which single cells organize and cooperate … read more
Many patients with chronic wounds will develop infection (Landis et al, 2007; Sibbald et al, 2011). Worldwide consensus on the specific use of silver antimicrobials recommends that silver dressings should be used initially for a ‘two-week challenge’ (Wounds International, 2012). Sixteen different individual case studies were carried out to evaluate the efficacy of a biofilm remover/cleanser in gel form, Prontosan® (B Braun), together with the use of an ionic releasing silver alginate, Askina® Calgitrol® Paste (B Braun) or Askina® Calgitrol® Thin (B Braun), when used on infected wounds. This study was completed in an advanced wound management centre in Pretoria, South Africa, during 2016. Selection criteria included wounds showing clinical signs of infection with delayed healing for more than 2 weeks. The study results showed that 50% of the wounds’ clinical signs of infection resolved within the 2-week antimicrobial challenge and by week 3, 81% of all clinical signs resolved. Ninety-three per cent of the wounds had improved wound progress and healing .. read more
Given the impact of infection on delayed wound healing, determining the presence of colonization and infection is imperative to achieving healed outcomes. Chronic wounds are always contaminated, and timely implementation of management and treatment interventions is a key component of the plan of care.
Diagnosis of infection can be a very challenging task to say the least, and it is further complicated by the presence of biofilms for which no diagnostic tool is currently available. If not addressed in a timely manner, these local infections can become systemic, leading to sepsis, multiple organ failure, and death. The first steps are a complete and thorough history and a physical examination of the whole patient, not just the patient’s wound, while taking into account both primary and secondary findings to understand the host response.
Having a thorough understanding of the principles of chronic wound care and of the current diagnostic modalities available is essential to the improvement of clinical outcomes and cost reduction related to the complication of wound infection. Our focus is on the challenges to diagnosing wound infection, including accurately determining risk factors, differentiating colonization from infection, and understanding the gold standard for diagnosing wound infection … read more
This 11 minute film is excerpted from an interview with Dr. Tim Lu, who is an expert in characterizing & eliminating biofilms with phage therapy. He offers some insightful ways to describe complex biofilms and their connection to antibiotic resistance.
Among the greatest triumphs of modern medicine were the identification and naming of the Penicillium mold by Alexander Fleming in 1928, and its ability to inhibit bacteria growth on culture medium. Penicillin was then developed by the team of Heatley, Chain, and Florey in England during the Second World War.1 This miracle brought about the ability to cure previously untreatable diseases and devastating infections that had high morbidity and mortality rates. Along with the great efficacy of penicillin was the added benefit of very few side effects. This area of research brought about the era of antibiotic production, which began in the 1950s.
Mechanisms of Antibiotic Resistance and Implications for Health Care
Antibiotics target one or multiple modes of cellular communication which allow microorganisms to proliferate. These include cell wall, membrane transport, RNA function, DNA synthesis, protein function, or enzyme activity.2 Interrupting cellular communication and thus proliferation has made antibiotics very effective against a broad range of microoganisms. In looking at the history of multidrug-resistant organisms (MDROs) we must remember that there are two sides to every coin, and with the positive side of clinical efficacy against microoganisms there is also a downside. To ensure their survival, it has become necessary for microorganisms to evolve and genetically mutate. These processes have caused the organisms of today to be much different from the organisms of yesterday, much more virulent, and more multidrug resistant … read more
Dr. Randy Wolcott has been practicing medicine for almost thirty years and focusing on treating “unhealable” wounds the last twelve. His personal research at the Wound Care Center’s Research and Testing Laboratories and his collaboration with biofilm experts in the wound care field have earned him international recognition. I met “Randy” in October of 2010 and interviewed him, staff members and his patients to get a sense of how advanced their diagnostic & treatment methods really were. Their treatment approach has set a new (and badly needed) standard of care for treating chronic bacterial biofilm infections.
Given the complexity of biofilm in lower extremity wounds, these authors offer a closer look on how biofilm develops, keys to eradicating biofilm and emerging modalities that may have an impact in the future.
We all encounter biofilms on a regular basis in our practices. A biofilm is a complex polymicrobal community of bacteria and fungi that develops on foreign materials, necrotic debris, exposed bone, and within the bed of chronic wounds. When James and colleagues examined the biopsies of 50 chronic wound beds, 60 percent contained a biofilm.
Planktonic or free-floating bacteria are more aggressive and divide more rapidly. Changes in gene expression allow them to secrete hydrolase enzymes and exotoxins, resulting in more rapid local tissue invasion. As a bacterial colony develops, environmental stimuli induce the cells to engage in quorum sensing, a gradient-based recruitment strategy used to summon additional bacteria to the developing biofilm and alter the phenotypic expression of bacteria within the community. Free-floating planktonic bacteria adhere to the wound bed using very weak molecular interactions … read more
Both chronic and acute dermal wounds are susceptible to infection due to sterile loss of the innate barrier function of the skin and dermal appendages, facilitating the development of microbial communities, referred to as biofilms, within the wound environment. Microbial biofilms are implicated in both the infection of wounds and failure of those wounds to heal. The aim of this review is to provide a summary of published papers detailing biofilms in wounds, the effect they have on infection and wound healing, and detailing methods employed for their detection. The studies highlighted within this paper provide evidence that biofilms reside within the chronic wound and represent an important mechanism underlying the observed, delayed healing and infection. The reasons for this include both protease activity and immunological suppression. Furthermore, a lack of responsiveness to an array of antimicrobial agents has been due to the biofilms’ ability to inherently resist antimicrobial agents. It is imperative that effective strategies are developed, tested prospectively, and employed in chronic wounds to support the healing process and to reduce infection rates. It is increasingly apparent that adoption of a biofilm-based management approach to wound care, utilizing the “antibiofilm tool box” of therapies, to kill and prevent reattachment of microorganisms in the biofilm is producing the most positive clinical outcomes and prevention of infection …. full article available for purchase or rent