Antibiotic treatment and resistance in chronic wounds of vascular origin

Tzaneva, Valentina; Mladenova, Irena; Todorova, Galina; Petkov, Dimitar

doi:10.15386/cjmed-647

Cited by 28 publications

(27 citation statements)

References 11 publications

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“…Polymicrobial infections in chronic wounds are responsible for poor clinical outcomes and cause elevated mortality rates as compared to single‐species infections (Tzaneva et al ). Colonizing species establish mutualistic relationship through multiple mechanisms including metabolite crossfeeding to promote community stability and resilience (West et al ; Ramsey et al ).…”

Section: Discussionmentioning

confidence: 99%

Metabolic modelling of chronic wound microbiota predicts mutualistic interactions that drive community composition

Phalak

Henson

2019

J Appl Microbiol

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Aims: To identify putative mutualistic interactions driving community composition in polymicrobial chronic wound infections using metabolic modelling. Methods and Results: We developed a 12 species metabolic model that covered 74% of 16S rDNA pyrosequencing reads of dominant genera from 2963 chronic wound patients. The community model was used to predict species abundances averaged across this large patient population. We found that substantially improved predictions were obtained when the model was constrained with genera prevalence data and predicted abundances were averaged over 5000 ensemble simulations with community participants randomly determined according to the experimentally determined prevalences. Staphylococcus and Pseudomonas were predicted to exhibit a strong mutualistic relationship that resulted in community growth rate and diversity simultaneously increasing, suggesting that these two common chronic wound pathogens establish dominance by cooperating with less harmful commensal species. In communities lacking one or both dominant pathogens, other mutualistic relationship including Staphylococcus/Acinetobacter, Pseudomonas/ Serratia and Streptococcus/Enterococcus were predicted consistent with published experimental data. Conclusions: Mutualistic interactions were predicted to be driven by crossfeeding of organic acids, alcohols and amino acids that could potentially be disrupted to slow chronic wound disease progression. Significance and Impact of the Study: Approximately 2% of the US population suffers from nonhealing chronic wounds infected by a combination of commensal and pathogenic bacteria. These polymicrobial infections are often resilient to antibiotic treatment due to the nutrient-rich wound environment and species interactions that promote community stability and robustness. The simulation results from this study were used to identify putative mutualistic interactions between bacteria that could be targeted to enhance treatment efficacy.

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Section: Discussionmentioning

confidence: 99%

Metabolic modelling of chronic wound microbiota predicts mutualistic interactions that drive community composition

Phalak

Henson

2019

J Appl Microbiol

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“…Bacteria in biofilms are at least tenfold more resistant to systemically as well as topically applied antibiotics than their planktonic variants, because of their improved survival mechanisms [8, 9]. They show slower growth rate, are able to transfer genes mediating resistances to antibiotics and, due to the EPS, the penetration of antibiotics and other biocides is aggravated [10–12].…”

Section: Introductionmentioning

confidence: 99%

Impact of probiotics on pathogen survival in an innovative human plasma biofilm model (hpBIOM)

et al. 2019

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Background Despite of medical advances, the number of patients suffering on non-healing chronic wounds is still increasing. This fact is attended by physical and emotional distress and an economic load. The majority of chronic wounds are infected of harmful microbials in a protecting extracellular matrix. These biofilms inhibit wound healing. Biofilm-growing bacteria developed unique survival properties, which still challenge the appropriate wound therapy. The present in-vitro biofilm models are not suitable for translational research. By means of a novel in-vivo like human plasma biofilm model (hpBIOM), this study systematically analysed the influence of 3 probiotics on the survival of five clinically relevant pathogenic microorganisms. Methods Human plasma was used to produce the innovate biofilm. Pathogenic microorganisms were administered to the plasma. By stimulating the production of a fibrin scaffold, stable coagula-like discs with integrated pathogens were produced. The five clinically relevant pathogens P. aeruginosa , S. aureus , S. epidermidis , E. faecium and C. albicans were challenged to the probiotics L. plantarum , B. lactis and S. cerevisiae . The probiotics were administered on top of the biofilm and the survival was quantified after 4 h and 24 h of incubation. For statistics, two-way ANOVA with post-hoc Tukey’s HSD test was applied. P-value > 0.05 was considered to be significant. Results SEM micrographs depicted the pathogens on the surface of the fibrin scaffold, arranged in close proximity and produced the glycocalyx. The application of probiotics induced different growth-reducing capacities towards the pathogens. B. lactis and S. cerevisiae showed slight bacteria-reducing properties. The survival of C. albicans was not affected at all. The most antimicrobial activity was detected after the treatment with L. plantarum . Conclusions This study successfully reproduced a novel human biofilm model, which provides a human wound milieu and individual immune competence. The success of bacteriotherapy is dependent on the strain combination, the number of probiotics and the activity of the immune cells. The eradicating effect of L. plantarum on P. aeruginosa should be emphasized.

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“…Indeed, microscopic analyses revealed, that 60-80% of chronic wounds are colonized by densely arranged mono-and polymicrobial communities, comprised of bacterial and/or fungal microorganisms. These microorganisms produce and reside within an extracellular polymeric substance (EPS) [4][5][6] . Various studies postulate, that persisting biofilms on chronic wounds negatively affect cellular behaviour in tissue repair processes, inflammatory cellular response and the innate immune system 7,8 .…”

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confidence: 99%

Efficacy of antiseptics in a novel 3-dimensional human plasma biofilm model (hpBIOM)

Besser

Dietrich

Weber

et al. 2020

Sci Rep

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The increasing incidence of non-healing wounds constitutes a pivotal socio-economic burden. 60-80% of chronic wounds are colonized by pathogenic microorganisms within a protective extracellular polymeric substance, bearing a great challenge in wound management. Human plasma was used to prepare the biofilm model (hpBIOM), adding pathogens to the plasma and forming Coagulalike discs with integrated pathogens were produced. The antiseptics Octenisept and Lavasorb were tested regarding their antibacterial properties on clinically relevant biofilm-growing bacteria (MRSA, P. aeruginosa) in the hpBIOM. Biofilm-typical glycocalyx-formation was confirmed using immunohistochemical staining. Treatment of a 12 h-maturated biofilm with Octenisept resulted in complete eradication of P. aeruginosa and MRSA after 48 h. Lavasorb proved less effective than Octenisept in this setting. In more mature biofilms (24 h), both antiseptics showed a delayed, partially decreased efficacy. Summarized, the hpBIOM provides essential factors for a translational research approach to be used for detailed human biofilm analyses and evaluation of antimicrobial/-biofilm properties of established and novel therapeutic strategies and products. Octenisept and Lavasorb showed an attenuated efficacy in the hpBIOM compared to planktonic conditions and previously published biofilm-studies, prompting the question for the necessity of introducing new international standards and pre-admission requirements on a translational base.

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Antibiotic treatment and resistance in chronic wounds of vascular origin

Cited by 28 publications

References 11 publications

Metabolic modelling of chronic wound microbiota predicts mutualistic interactions that drive community composition

Metabolic modelling of chronic wound microbiota predicts mutualistic interactions that drive community composition

Impact of probiotics on pathogen survival in an innovative human plasma biofilm model (hpBIOM)

Efficacy of antiseptics in a novel 3-dimensional human plasma biofilm model (hpBIOM)

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