Microbial biofilms for diabetic foot ulcers

NewsBot · Jul 15, 2007

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Press Release:
Kane Biotech Announces Positive Results From an Independent Wound Care Study

WINNIPEG, MANITOBA--(Marketwire - July 11, 2007) - Kane Biotech Inc. (TSX VENTURE:KNE), a biotechnology company engaged in the development of products that prevent and disperse microbial biofilms, is pleased to announce positive results from an in vitro study using a novel approach to treat chronic wound infections with a combination of DispersinB and lytic bacteriophage.

The study carried out by Dr. Randy Wolcott's team at the Southwest Regional Wound Care Center in Lubbock, Texas, showed that the combination of DispersinB with a bacteriophage mixture was very effective against biofilm-embedded E.coli. More specifically, the DispersinB and bacteriophage mixture showed almost 99% inhibition of E.coli growth and proliferation as compared to only 9% inhibition by the bacteriophage mixture alone over the four day period of treatment. While DispersinB makes biofilm-embedded bacteria more susceptible to bacteriophage by inhibiting or dispersing biofilms, lytic bacteriophage invades bacterial cells and disrupts the metabolism of the bacteria. This combination therapy could provide a new and highly effective method of treating chronic wounds such as diabetic foot ulcers.

"DispersinB degrades the defences of the biofilm, providing a synergistic effect when combined with bacteriophages. Our findings are very encouraging as DispersinB may also enhance the effectiveness of a number of antimicrobial agents in the treatment of chronic wounds" stated Dr. Wolcott. "I believe that DispersinB will also prove effective against other wound infection associated bacteria in combination with other antimicrobials and we are continuing our studies in this area."

"DispersinB is one of our lead technologies to prevent and disperse biofilms and is proving to have very broad applications in the medical field. This study adds further evidence to the growing knowledge base on the value of our technology", stated Gord Froehlich, President and CEO of Kane Biotech.

Chronic wounds are a serious debilitating complication of vascular disease, diabetes and prolonged immobility and are a huge unmet clinical need that costs the US health care system $20 billion per year. The current global market for wound care management technology is estimated at US$4.5 billon per year.

"Our DispersinB technology prevents and removes biofilms while the bacteriophages and antimicrobial agents offer broad spectrum microbial control. As a naturally occurring non-antibiotic antibiofilm enzyme, DispersinB is a compelling technology for clinical settings", added Mr. Froehlich.
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NewsBot · Jul 14, 2016

Bacteriophage treatment of intransigent diabetic toe ulcers: a case series.
Fish R et al
J Wound Care. 2016 Jul;25(Sup7):S27-S33.

OBJECTIVE:
Diabetic foot ulcer (DFU) infections are a growing public health problem, with increasing prevalence, poor response to antibiotics and bacterial resistance to traditional antimicrobials leading to increased morbidity and mortality. Bacteriophages (phages), the viruses that target specific bacteria, are one option for addressing bacterial infections, especially where antibiotics fail. Of particular value is a class of virulent staphylococcal phages that hit almost all Staphylococcus aureus, including most methicillin-resistant Staphylococcus aureus (MRSA) strains. Here we report a continuous case series assessing the effectiveness of treating infected and poorly vascularised toe ulcers with exposed bone, after failure of recommended antibiotic therapy, using topically applied Staphylococcus aureus-specific phage.
METHOD:
This was a compassionate-use case series of nine patients with diabetes and poorly perfused toe ulcers containing culture-proven Staphylococcus aureus infected bone and soft tissue, who had responded poorly to recommended antibiotic therapy. Six representative cases are presented here. The only generally accepted other option in each case was toe amputation. Exposed portions of the infected phalanges were removed in three cases and left in place in two cases. One case presented as a micro-clot induced gangrene following vascular stenting. In this case, phage were used to prevent infection. The phage used was a commercially available fully sequenced preparation of staphylococcal phage Sb-1. Phage solution was applied topically to the ulcerations once weekly, following standard good wound care. The amount of phage solution applied varied from 0.1 to 0.5 cc depending on volume and area of the ulceration.
RESULTS:
All infections responded to the phage applications and the ulcers healed in an average of seven weeks with infected bone debridement. One ulcer, where vascularity was extremely poor and bone was not removed to preserve hallux function, required 18 weeks of treatment. In the case of the toe with the micro-clot gangrene, the toe was salvaged and healed in seven weeks without complications.
CONCLUSION:
Topical application of a staph mono-phage preparation can be used successfully to treat infected toe ulcerations with bone involvement, despite very poor vascularity and failure of antibiotic treatment. The success within this small series provides the groundwork for controlled clinical trials of staph phage for diabetic foot infections.
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NewsBot · Nov 10, 2017

Bacteriophage Treatment of Infected Diabetic Foot Ulcers.
Morozova VV et al
Methods Mol Biol. 2018;1693:151-158. doi: 10.1007/978-1-4939-7395-8_13.

Diabetic foot ulcers occur as a common complication of diabetes. Healing of the ulcers is largely delayed by the concomitant infection. Antibiotic treatment of infected ulcers is complicated by formation of microbial biofilms , which are often heterogeneous and resistant to antibiotics. Bacteriophage therapy is considered as an additional approach to the treatment of infected wounds. Here, we describe the basic method of application of bacteriophages for treatment of infected diabetic foot ulcers, including ones that are very large.
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NewsBot · Nov 22, 2022

Bacteriophage therapy as an alternative technique for treatment of multidrug-resistant bacteria causing diabetic foot infection
Amira Mohamed Ghanaim et al
Int Microbiol. 2022 Nov 9

Diabetic foot ulcer (DFU) represented the most feared diabetic complication that caused the hospitalization of the diabetic patient. DFU was usually characterized with delayed healing as the diabetic neuropathy, angiopathy, and ulcer concomitant infections, among them, are multidrug-resistant (MDR) bacteria that emphasized the clinical importance for developing new therapeutic strategy with safe and effective alternatives for the antibiotics to overcome DFU-MDR bacterial infection. Bacteriophage therapy was considered a novel approach to eradicate the MDR, but its role in the polymicrobial infection of the DFU remains elusive. Thus, the current work was designed to investigate the effect of the topical application of the phage cocktail on the healing of the diabetic wound infected with clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella variicola, Escherichia coli, and Proteus mirabilis. Bacterial isolation was performed from clinical hospitalized and non-hospitalized cases of DFU, identified morphologically, biochemically, molecularly via 16 s rRNA sequencing, and typed for the antibiotic resistance pattern. Moreover, phages were isolated from the aforementioned clinical isolates and identified with electron microscope. Forty-five adult male Sprague-Dawley rats were assigned in 3 groups (15 rats each), namely, the diabetic infected wound group, diabetic infected wound ceftriaxone-treated group, and the diabetic infected wound phage cocktail-treated group. The results revealed that phage cocktail had a superior effect over the ceftriaxone in wound healing parameters (wound size, wound index, wound bacterial load, and mRNA expression); wound healing markers (Cola1a, Fn1, MMP9, PCNA, and TGF-β); inflammatory markers (TNF-α, NF-κβ, IL-1β, IL-8, and MCP-1); anti-inflammatory markers (IL-10 and IL-4); and diabetic wound collagen deposition; and also the histomorphic picture of the diabetic infected wound. Based on the current findings, it could be speculated that phage therapy could be considered a novel antibiotic substitute in the DFU with MDR-polymicrobial infection therapeutic strategies.
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NewsBot · Jul 26, 2023

Phage Therapy for Diabetic Foot Infection: A Case Series
Matthew J Young et al
Clin Ther. 2023 Jul 11

Purpose: Infected diabetic foot ulcers can be difficult to treat and, despite appropriate antibiotic therapy, some diabetic foot infections (DFIs) require amputation. Bacteriophages (phages) are viruses that infect and kill bacteria. Phage therapy has been repeatedly used to successfully treat DFIs and other chronic wounds.

Methods: This article reports the provision of topical adjunctive anti-staphylococcal phage therapy to 10 patients with DFI at high risk of amputation at two UK hospitals as part of clinical care; tolerability and efficacy were clinically assessed.

Findings: The opinion of the experienced clinical teams caring for these patients was that 9 of the 10 patients appeared to benefit from adjunctive phage therapy. No adverse effects were reported by clinicians or patients. In 6 of 10 patients the clinical impression was that phage therapy facilitated clinical resolution of infection and limb salvage. Resolution of soft tissue infection was observed in a 7th patient but unresolved osteomyelitis required amputation. An 8th patient demonstrated eradication of Staphylococcus aureus from a polymicrobial infection and a 9th showed signs of clinical improvement before early cessation of phage therapy due to an unrelated event. One patient, with a weakly susceptible S aureus isolate, had no significant response.

Implications: This report describes the largest application of phage therapy in the United Kingdom to date and the first application of phage therapy for DFI in the United Kingdom and offers subjective hints toward impressive tolerability and efficacy. Phage therapy has the potential to transform the prevention and treatment of DFIs.
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NewsBot · Aug 18, 2023

Phage therapy for diabetic foot infection
Joshua D Jones, Lesley ML Hall, Matthew J. Young
7 February 2023

The treatment of diabetic foot infections (DFIs) represents a costly and growing challenge to the NHS. DFIs can be difficult to treat for a variety of reasons, including late presentation of advanced infection, and antibiotic tolerance or resistance. Bacteriophage (phage) are ubiquitous viruses that infect and kill bacteria in a species-, sometimes even strain-, specific manner. Phages have been used to treat bacterial infection since 1919, but their use in the geopolitical West ceased in the 1930s due to a variety of factors, including the mass production of antibiotics. The modern antibiotic resistance crisis has driven renewed interest in phage therapy and 2,241 patients with mostly with antibiotic refractory infections have been treated since 2000, 79% of whom improved. This includes at least 310 patients with chronic wound infections, among whom 86.1% achieved clinical resolution or improvement of infection. Reassuringly, the available evidence suggests that phage therapy is safe and without notable side effects. Some phages also possess enzymes capable of degrading the biofilms that afford antibiotic tolerance to bacteria and underpin many chronic infections. Phages also act independent of antibiotic resistance, allowing the treatment of even pan-resistant bacteria, and topical or local application to DFIs means antimicrobial activity is independent of a patient’s peripheral perfusion. Presently only an option when antibiotics are not meeting a patient’s clinical needs, future integration of phage therapy at all levels of DFI care will radically transform the outlook for DFIs in the UK. Reducing the number of serious infections and amputations will not only benefit patients but will deliver vast savings to the NHS and reduce the amount of antibiotics used, making phage therapy a tangible response to the antibiotic resistance crisis.
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NewsBot · Jan 1, 2024

Bacteriophage Treatment of Infected Diabetic Foot Ulcers
Vera V Morozova et al
Methods Mol Biol. 2024:2734:197-205

Diabetic foot ulcers occur as a common complication of diabetes. The concomitant infection significantly delays the healing of the ulcers. Antibiotic treatment of infected ulcers is complicated by the formation of microbial biofilms, which are often heterogeneous and resistant to antibiotics. Bacteriophage therapy is considered an additional approach to the treatment of infected wounds. Here, we describe the basic method of application of bacteriophages for the treatment of infected diabetic foot ulcers, including very large ones.
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NewsBot · Feb 22, 2024

Lytic activity of phages against bacterial pathogens infecting diabetic foot ulcers
Legesse Garedew Kifelew et al
Sci Rep. 2024 Feb 12;14(1):3515

Complications of diabetes, such as diabetic foot ulcers (DFUs), are common, multifactorial in origin, and costly to treat. DFUs are the cause of nearly 90% of limb amputations among persons with diabetes. In most chronic infections such as DFU, biofilms are involved. Bacteria in biofilms are 100-1000 times more resistant to antibiotics than their planktonic counterparts. Multidrug-resistant (MDR) Staphylococcus aureus and Pseudomonas aeruginosa infections in DFUs may require alternative therapeutic agents such as bacteriophages ("phages"). This study describes the lytic activity of phage cocktails AB-SA01 (3-phage cocktail) and AB-PA01 (4-phage cocktail), which target S. aureus and P. aeruginosa, respectively. The host range and lytic effect of AB-SA01 and AB-PA01 on a planktonic culture, single-species biofilm, and mixed-species biofilm were evaluated. In vitro testing showed that 88.7% of S. aureus and 92.7% of P. aeruginosa isolates were susceptible to AB-SA01 and AB-PA01, respectively, in the planktonic state. The component phages of AB-SA01 and AB-PA01 infected 66% to 94.3% of the bacterial isolates tested. Furthermore, AB-SA01 and AB-PA01 treatment significantly (p < 0.05) reduced the biofilm biomass of their hosts, regardless of the antibiotic-resistant characteristics of the isolates and the presence of a non-susceptible host. In conclusion, the strong lytic activity, broad host range, and significant biofilm biomass reduction of AB-SA01 and AB-PA01 suggest the considerable potential of phages in treating antibiotic-resistant S. aureus and P. aeruginosa infections alone or as coinfections in DFUs.
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Microbial biofilms for diabetic foot ulcers

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Microbial biofilms for diabetic foot ulcers

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Eliminate Shoe Odor: The Battle Between Anti-Odor and Antimicrobial Solution

Topical antimicrobial agents for treating foot ulcers in people with diabetes.

WHO release policy document on Antimicrobial Resistance

Expression of antimicrobial peptides in diabetic foot ulcer.

Nail surgery - Do you use any anti-microbial dressing?

Topical Antimicrobials in the Control of Wound Bioburden

Foot odor due to microbial metabolism and its control

Share This Page

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