The Potential of Bacteriophage Therapy as an Alternative Treatment Approach for Antibiotic-Resistant Infections.

OBJECTIVE: This study aimed to provide a comprehensive overview of the current state of the literature on the therapeutical application of bacteriophages. METHODS: First, a bibliometric analysis was performed using the database Web of Science to determine annual number of publications and citations. Second, a systematic literature review was conducted on randomized-controlled trials (RCTs) of phage therapy in PubMed. RESULTS: Over the past decade, the number of publications on bacteriophage therapy increased more than fourfold with 212 articles in 2011 and 739 in 2022. The systematic search in PubMed yielded 7 RCTs eligible for inclusion, reporting on a total of 418 participants. Identified indications in this study included bacterial diarrhea, urinary tract infections, infected burn wounds, chronic otitis, chronic venous leg ulcers, and chronic rhinosinusitis. In three studies, mild to moderate adverse events were reported in 10/195 participants (5.1%). Three of the studies reported a statistically significant difference in outcomes comparing phage therapy with standard of care or placebo. CONCLUSION: Phage therapy has gained increasing interest over the years. RCTs on different indications suggest the safety of phage therapy; however, reasons why phage therapy is not yet well accepted are limitations in the study designs. For a successful translation into clinical practice researchers and clinicians should learn from the earlier experiences and consider issues such as the quality of phage preparation, sensitivity testing, titer and dosages, as well as access to the infection site and stability for standardized protocols and future trials.

Calcified Leg Ulcers in Older Patients: Clinical Description, Morphology, and Chemical Characterization.

Chronic wounds, including leg ulcers, constitute an important medical problem among older patients. Dystrophic calcifications (DC) are associated with a variety of disorders, including leg ulcers. The aim of this study was to report the clinical and biological characteristics of older patients with DC in leg ulcers and to determine the morphology and chemical composition of these calcifications. We conducted a prospective monocentric study in our Geriatric-Wound and Healing ward, Rothschild Hospital, Paris, from January 2018 to December 2019. Patients with leg ulcers were screened for DC by palpation. Patients' clinical, biological, and radiological findings were collected. DC morphology was analyzed using field-emission scanning electron microscopy and chemical composition was analyzed using µFourier transform infra-red spectroscopy and X-ray Fluorescence. Ten (7%) of the 143 patients hospitalized for leg ulcers presented DC. Older patients with DC were more likely to have leg ulcers with venous insufficiency (p = .015), colonized by Pseudomonas aeruginosa (p = .026), with a longer healing evolution (p = .0072) and hypercalcemia (p = .041). Five DC were extracted from ulcers: 2 presented 500 nm lacunar spheres and intermingled fibrils of about 10 nm in diameter, consistent with bacterial and biofilm imprints. DC were always composed of calcium-phosphate apatite and associated to the presence of zinc. Our analyses were consistent with the involvement of microorganisms and inflammatory process in DC formation. Early management of venous insufficiency, treatment of chronic bacterial colonization and use of calcium-solubilizing drugs seem to be rational strategies for calcified leg ulcer management in older patients.

Prospective clinical study on the efficacy of bacterial removal with mechanical debridement in and around chronic leg ulcers assessed with fluorescence imaging.

Bacterial colonisation in wounds delays healing, mandating regular bacterial removal through cleaning and debridement. Real-time monitoring of the efficacy of mechanical debridement has recently become possible through fluorescence imaging. Red fluorescence, endogenously produced during bacterial metabolism, indicates regions contaminated with live bacteria (>104 CFU/g). In this prospective study, conventional and fluorescence photos were taken of 25 venous leg ulcers before and after mechanical debridement, without use of antiseptics. Images were digitally segmented into wound bed and the periwound regions (up to 1.5 cm outside bed) and pixel intensity of red fluorescence evaluated to compute bacterial area. Pre-debridement, bacterial fluorescence comprised 10.4% of wound beds and larger percentages of the periwound area (~25%). Average bacterial reduction observed in the wound bed after a single mechanical debridement was 99.4% (p<0.001), yet periwound bacterial reduction was only 64.3%. On average, across bed and periwound, a single mechanical debridement left behind 29% of bacterial fluorescence positive tissue regions. Our results show the substantial effect that safe, inexpensive, mechanical debridement can have on bacterial load of venous ulcers without antiseptic use. Fluorescence imaging can localise bacterial colonised areas and showed persistent periwound bacteria post-debridement. Fluorescence-targeted debridement can be used quickly and easily in daily practice.

Er:YAG laser vs. sharp debridement in management of chronic wounds: Effects on pain and bacterial load.

Chronic wounds affect roughly 6.5 million patients in the US annually. Current standard of therapy entails weekly sharp debridement. However, the sharp technique is associated with significant pain, while having minimal impact on the bioburden. Our study proposes the Er:YAG laser as an alternative method of debridement that may decrease procedural pain, reduce bioburden, and potentially improve overall healing. This pilot study was performed as a prospective, randomized, controlled, crossover clinical trial, containing two groups: (1) one group underwent single laser debridement session first, followed by single sharp debridement session one week later; and (2) the other group underwent single sharp debridement session first, followed by single laser debridement session one week later. Variables analyzed included pain during debridement, pre- and post-debridement wound sizes, pre- and post-debridement bacterial loads and patient preference. Twenty-two patients were enrolled (12 patients in Group 1, plus 10 patients in Group 2). The mean pain score for patients undergoing laser debridement was 3.0 ± 1.7 vs. 4.8 ± 2.6 for those undergoing sharp debridement (p = 0.003). The mean percent change in wound size 1-week post-laser debridement was -20.8% ± 80.1%, as compared with -36.7% ± 54.3% 1-week post-sharp debridement (p = 0.6). The percentage of patients who had a bacterial load in the low/negative category increased from 27.3% to 59.1% immediately after laser debridement (p = 0.04), vs. 54.5% to 68.2% immediately after sharp debridement (p = 0.38). Moreover, there was a sustained decrease in bacterial load 1-week post-laser debridement, as compared with no sustained decrease 1-week post-sharp debridement (p < 0.02). Overall, 52.9% of patients preferred laser debridement vs. 35.3% for sharp debridement. We believe that Er:YAG laser serves as a promising technology in chronic wounds, functioning as a potentially superior alternative to sharp debridement, the current standard of therapy.

Real-time bacterial fluorescence imaging accurately identifies wounds with moderate-to-heavy bacterial burden.

OBJECTIVE: Clinical evaluation of signs and symptoms (CSS) of infection is imperative to the diagnostic process. However, patients with heavily colonised and infected wounds are often asymptomatic, leading to poor diagnostic accuracy. Point-of-care fluorescence imaging rapidly provides information on the presence and location of bacteria. This clinical trial (#NCT03540004) aimed to evaluate diagnostic accuracy when bacterial fluorescence imaging was used in combination with CSS for identifying wounds with moderate-to-heavy bacterial loads. METHODS: Wounds were assessed by study clinicians using NERDS and STONEES CSS criteria to determine the presence or absence of moderate-to-heavy bacterial loads, after which the clinician prescribed and reported a detailed treatment plan. Only then were fluorescence images of the wound acquired, bacterial fluorescence determined to be present or absent and treatment plan adjusted if necessary. RESULTS: We examined 17 VLUs/2 DFUs. Compared with CSS alone, use of bacterial fluorescence imaging in combination with CSS significantly improved sensitivity (22% versus 72%) and accuracy (26% versus 74%) for identifying wounds with moderate-to-heavy bacterial loads (≥104 CFU/g, p=0.002). Clinicians reported added value of fluorescence images in >90% of study wounds, including identification of wounds incorrectly diagnosed by CSS (47% of study wounds) and treatment plan modifications guided by fluorescence (73% of study wounds). Modifications included image-guided cleaning, treatment selection, debridement and antimicrobial stewardship. CONCLUSION: Findings from this pilot study suggest that when used in combination with CSS, bacterial fluorescence may: (1) improve the diagnostic accuracy of identifying patients with wounds containing moderate-to-heavy bacterial loads and (2) guide more timely and appropriate treatment decisions at the point-of-care.

Antibiogram in the biopsy of chronic venous ulcers related to sudden changes in the pain profile.

INTRODUCTION: Chronic venous insufficiency (CVI) has an important impact on the public health system in particular due to the occurrence of chronic venous ulcers (UCV) and infections. OBJECTIVE: To evaluate cultures of biopsies of chronic venous ulcers of patients who suffered an acute change in the intensity of pain of the lesion. METHOD: Antibiograms of the cultures of chronic venous ulcer biopsies of patients who suffered an acute change in the lesion with significant pain for 24 hours were evaluated. All patients were treated between 2011 and 2015 in the Vascular Surgery Outpatient Clinic of the Medical School in São José do Rio Preto. Other causes of pain such as chronic arterial insufficiency and problems with the dressings were ruled out. RESULTS: Positive cultures were detected in 34 of the 35 patients whose pain was resolved by antibiotic therapy. CONCLUSION: Acute changes in the intensity of pain associated with chronic venous ulcers seem to be related to local infectious disease.

Evaluation of wound fluid biomarkers to determine healing in adults with venous leg ulcers: A prospective study.

Clinical practice guidelines recommend using repeated wound surface area measurements to determine if a chronic ulcer is healing. This results in delays in determining the healing status. This study aimed to evaluate whether any of a panel of biomarkers can determine the healing status of chronic venous leg ulcers. Forty-two patients with chronic venous leg ulcers had their wound measured and wound fluid collected at weekly time points for 13 weeks. Wound fluid was analyzed using multiplex enzyme-linked immunosorbent assay to determine the concentration of biomarkers in the wound fluid at each weekly time point. Healing status was determined by examining the change in wound size at the previous and subsequent weeks. Predictive accuracy with 95% confidence intervals (CI) is reported. Of 42 patients, 105 evaluable weekly time points were obtained, with 32 classified as healing, 27 as nonhealing, and 46 as indeterminate. Thirteen biomarkers significantly differed between healing and nonhealing wounds (p < 0.1) and were included in a multivariate logistic regression model. Granulocyte macrophage-colony stimulating factor (p < 0.001) and matrix metalloprotease-13 (p = 0.004) were the best predictors of wound healing. Receiver operating characteristic curves indicated 92% accuracy (95% CI: 85%,100%) for granulocyte macrophage-colony stimulating factor, and 78% accuracy (95% CI: 65%,90%) for matrix metalloprotease-13 in discriminating between healing and nonhealing wounds. This study found that two biomarkers from wound fluid can predict healing status in chronic venous leg ulcers. These findings may lead to the ability to determine the future trajectory of a wound and the ability to modify treatment accordingly.

The diagnosis of infection in chronic leg ulcers: A narrative review on clinical practice.

This literature review aimed to provide a narrative review of evidence on validity of clinical and microbial indicators of infection and to gain insights into the diagnosis of infection in chronic leg ulcers (CLUs). A search was conducted in Cinahl, Medline, the Cochrane Library databases, Embase, Web of Science, ScienceDirect, Pubmed, PsycINFO, ProQuest dissertations, and Google Scholar from January 1990 to July 2017. The inclusion criteria were original studies, systematic reviews, and consensus documents focused on "infection" in CLUs, English language, clinical and community settings, and human. The reviewed studies were inconsistent in criteria for infection between investigated wound types and lack of specificity regarding wound types. There were few studies investigating the criteria for diagnosis of infection in leg ulcers. The identification of leg ulcer infection still remains problematic and relies on out-of-date and not uniform evidence. Literature in this area was mostly limited to level III and IV evidence based on The Australian National Health and Medical Research Council Levels of Evidence, or expert opinion. This literature review showed seven clinical signs and symptoms that could be diagnostic for infection in CLUs, including: new, increased, or altered ulcer pain; malodour; increased ulcer area; wound breakdown, delayed or non-healing; and erythema and increased local temperature, whilst the microbial indicators used to diagnose infected leg ulcers were varied and regarded as less important.

A case study of venous leg ulceration.

Venous ulcers or stasis ulcers account for 80% of lower extremity ulcerations. Approximately 1-2% of the population will suffer from the chronic debilitating condition, with chronic venous insufficiency affecting up to 50% of the adult population. There are many methods of treatment and common treatments include conventional, surgical or mechanical methods. This article examines the complications of leg ulcer management, with the emphasis on the use of antibiotics. The case study demonstrates the positive impact self-care can have as part of a treatment plan.

Impact of Gram-negative bacteria on the treatment of venous leg ulcers.

Gram-negative germs with and without multi-resistance are garnering more and more importance. The aim of this study was to investigate the frequency and rate of resistance against antibiotics and to clarify the impact of Gram-negative bacteria, especially with high rates of resistance, for the treatment of venous leg ulcers. This is a retrospective, monocentric, non-randomised open study. Included were all data within 1 year of bacterial swabs of venous leg ulcers. We performed summarization, pooling, and descriptive analysis for frequencies and crossover. We analysed 679 swabs of 285 patients with venous leg ulcers. The mean patient age was 69.78 years. There were 76.1% Gram-positive and 58.2% Gram-negative germs detected; 56.5% of the swabs showed multi-resistance. Gram-negative bacteria were associated with more pain. Exacerbation and relevant aggravation of wounds that led to stationary treatment occurred more frequently. With polihexanid treatment, we saw less Gram-negative flora. This study showed an immediate impact of Gram-negative germs on the patient's pain, the risk for aggravation, and the choice of treatment. Further studies for prophylaxis and treatment of Gram-negative germs in venous leg ulcer therapy are needed.

The Impact of Microbial Communities on Wound Healing: A Review.

Chronic, nonhealing wounds place an enormous burden on both the health care system and patients, with no definitive treatments available. There has been increasing evidence that the microbial composition of wounds may play an important role in wound healing. Culture-independent methods for bacterial detection and analysis have revealed the wound microbiome to be much more diverse and complex than culture alone. Such methods primarily rely on targeted amplification and sequencing of various hypervariable regions of the bacterial 16S rRNA for phylogenetic analysis. To date, there have been several studies utilizing culture-independent methods to investigate the microbiome of a variety of chronic wounds, including venous insufficiency ulcers, pressure ulcers, and diabetic foot ulcers. Major bacteria found include Staphylococcus, Streptococcus, Corynebacterium, Pseudomonas, and various anaerobes. Current studies suggest that improved healing and outcomes may be correlated with increased bacterial diversity and instability of the microbiome composition of a wound. However, the exact role of the microbiome in wound healing remains poorly understood. While the current research is promising, studies are very heterogeneous, hindering comparisons of findings across different research groups. In addition, more studies are needed to correlate microbiome findings with clinical factors, as well as in the relatively unexplored fields of acute wounds and nonbacterial microbiomes, such as the wound mycobiome and virome. Better understanding of the various aspects of the microorganisms present in wounds may eventually allow for the manipulation of the wound microbiota in such a way as to promote healing, such as through bacteriophage therapies or probiotics.

Optimal Compression Therapy and Wound Care for Venous Ulcers.

Venous leg ulcers remain a major public health issue with significant economic impact. Two main components of the management of patients with venous leg ulcers are compression therapy and wound care. This article addresses principles and specific aspects of compression therapy and focal wound care for patients with venous leg ulcers.

Are there clinical signs and symptoms of infection to indicate the presence of multidrug-resistant bacteria in venous ulcers?

The selection of topical and systemic therapies for the treatment of venous ulcers with signs of infection is challenging and should be accompanied by specific precautionary measures to protect against cross-contamination in the presence of multidrug-resistant microorganisms. However, there are still no clinical indicators for this situation, and confirmation of resistant strains occurs through culture and sensitivity, which can take up to 14 days. During this period, protective measures may no longer be taken, contributing to the spread of these pathogens. This study aimed to analyze the relationship between clinical signs and symptoms of infection in venous ulcers and the presence of antimicrobial-resistant Staphylococcus aureus and/or Pseudomonas spp. A cross-sectional study was developed including 69 patients with 98 venous ulcers. Clinical observation protocol was applied to detect infection indicators established by the European Wound Management Association and microbiological analysis of samples of the lesions. Fisher's exact test and χ2 were used for analyses (P < 0.05). Two indicators of infection predominated (f >70%): discoloration of the opaque type and/or dark brick red and increased exudate volume; 31 (31.6%) ulcer samples showed positive culture for the bacteria studied. There was no relationship between signs and symptoms of infection and the presence of multidrug-resistant microorganisms. Taking into account the percentage of lesions with resistant strains, for safe care, contact precautionary measures should be implemented in the treatment rooms, in addition to standard precautions.

Disruption of Biofilms and Neutralization of Bacteria Using Hypochlorous Acid Solution: An In Vivo and In Vitro Evaluation.

OBJECTIVES: The aims of this study were to assess the effectiveness of a hypochlorous acid-based wound cleanser (Vashe Wound Solution [VWS], SteadMed Medical, Fort Worth, Texas) in disrupting methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa biofilms relative to other cleansers using an in vitro collagen biofilm model and to evaluate cleansers' cytotoxicity. The bioburden reduction of venous stasis wounds by VWS and another cleanser was evaluated. METHODS: Plates coated with collagen films incubated with active bacteria cultures to yield biofilm mimics were treated with VWS, 1% and 10% povidone-iodine (PI), 0.05% chlorhexidine wound solution (CWS), or normal saline for 3 or 10 minutes. Biofilms were then analyzed for biomass density using a crystal violet assay, quantitative cultures, and fluorescent microscopy. Cytotoxicity was measured using neutral red uptake by primary human dermal fibroblasts. Pre- and postcleansing exudates and swab samples obtained from venous stasis wounds of patients were processed and plated on a series of selective agar plates for bacteria typing and quantification. RESULTS: All agents tested significantly neutralized methicillin-resistant S aureus and P aeruginosa biofilms compared with saline control as assessed by crystal violet assay and fluorescent microscopy assays. Undiluted VWS was significantly less cytotoxic compared with 1% PI, CWS, and 10% PI (in increasing order of cytotoxicity). There was no significant difference in bacterial reduction in wounds after treatment with VWS or CWS for any type of bacteria examined using selective media. In wounds that were treated with VWS or CWS, there was a similar percentage reduction in bacterial colony-forming units from precleansing levels when plated on tryptic soy agar, MacConkey, streptococcal, and mannitol salt agar plates. Plates treated with CWS trended toward higher bacterial reduction on nonselective and gram-negative agars, whereas VWS trended toward higher bacterial reduction in Streptococcus-selective agars. CONCLUSIONS: These findings support the use of VWS in the treatment of wounds with biofilms and to reduce the bioburden of venous stasis ulcers. While VWS-treated biofilms had higher biomass than CWS- and saline-treated biofilms, most of the cellular component was not viable. Ultimately, VWS had a similar effectiveness to CWS in eliminating bacteria but with lower cytotoxicity.

Maltodextrin/ascorbic acid stimulates wound closure by increasing collagen turnover and TGF-ß1 expression in vitro and changing the stage of inflammation from chronic to acute in vivo.

It has been reported that carbohydrates confer physicochemical properties to the wound environment that improves tissue repair. We evaluated in vitro and in vivo wound healing during maltodextrin/ascorbic acid treatment. In a fibroblast monolayer scratch assay, we demonstrated that maltodextrin/ascorbic acid stimulated monolayer repair by increasing collagen turnover coordinately with TGF-ß1 expression (rising TGF-ß1 and MMP-1 expression, as well as gelatinase activity, while TIMP-1 was diminished), similar to in vivo trends. On the other hand, we observed that venous leg ulcers treated with maltodextrin/ascorbic acid diminished microorganism population and improved wound repair during a 12 week period. When maltodextrin/ascorbic acid treatment was compared with zinc oxide, almost four fold wound closure was evidenced. Tissue architecture and granulation were improved after the carbohydrate treatment also, since patients that received maltodextrin/ascorbic acid showed lower type I collagen fiber levels and increased extracellular alkaline phosphatase activity and blood vessels than those treated with zinc oxide. We hypothesize that maltodextrin/ascorbic acid treatment stimulated tissue repair of chronic wounds by changing the stage of inflammation and modifying collagen turnover directly through fibroblast response.

[Comparative study of the efficacy of larva therapy for debridement and control of bacterial burden compared to surgical debridement and topical application of an antimicrobial]. / Estudio comparativo de la eficacia de la larvaterapia (LT) para desbridar y controlar la carga bacteriana en úlceras venosas comparado con desbridamiento quirúrgico y aplicación de un antimicrobiano tópico.

Maggot debridement therapy (MDT) is the use of medical grade maggots of the fly Lucilia sericata for wound debridement. Recent observations show that MDT decreases bacterial burden as well. Venous ulcers are the most commonly seen in wound clinics and require, besides adequate treatment of venous hypertension, proper wound bed preparation with debri dement of necrotic tissue and control of potential infections. To evaluate the efficacy of MDT in venous ulcers a randomized controlled trial was designed to compare MDT to surgical debridement and topical application of silver sulfadiazine (SSD) in 19 patients for 4 weeks. The study variables were area reduction, wound bed characteristics, pain, odor, anxiety and bacterial burden using quantitative tissue biopsies. MDT was effective as surgical debridement associated with topical SDD in the debridement of the wound and in reducing its size. A significant difference was observed in the reduction of bacterial burden in favor of the MDT group. Odor and anxiety increased in the MDT group without any difference in the pain intensity between groups. In conclusion, this study suggests that MDT is as effective as surgical debridement for the debridement of necrotic tissue and promote wound healing in venous ulcers and better at reducing bacterial burden.

[When to worry about before a vascular chronic leg ulcer?]. / Quand s'inquiéter devant un ulcère de jambe d'origine vasculaire ?

Leg ulcers are a chronic condition. Healing can be long for venous ulcers and the risk of complications is significant. Infection is the most severe complication and can occur in the form of easily diagnosed acute bacterial dermohypodermitis that generally responds well to antibiotic treatment if given at an appropriate dose or in the form of localized infection that is more difficult to diagnosis. Indeed, no consensus has been reached in the literature on the clinical criteria to retain for the diagnosis of localized infection. Similarly, the most appropriate treatment remains to be established. Local care would be a logical starting point, followed by systemic antibiotics if this approach is unsuccessful. Individual conditions also should be taken into consideration (immunodepression, severe arteriopathy warranting more rapid use of systemic antibiotics). The second most frequent complication is an allergic reaction to a topical agent used for wound care. The rate of sensitivization in patients with leg ulcers is high (60 %), although the rate is declining with modern dressings. No product can be considered perfectly safe for these polysensitized patients. Dermocorticoid therapy can be very effective. Allergology tests are needed. Certain leg ulcers require special care from diagnosis. An arterial origin must be suspected for deep, or necrotic ulcers. Arterial supply must be explored rapidly, followed by a revascularization procedure when necessary. Highly painful superficial extensive necrotic ulcers due to necrotic angiodermitis require hospital care for skin grafts that will control the antiodermitis and provide pain. Carcinoma should be suspected in cases of leg ulcers with an atypical localization exhibiting excessive budding. A biopsy is mandatory for leg ulcers with an unusual course (absence of healing despite well-conducted care).

Evaluation of Early Surgical Treatment Results Considering Venous Leg Ulcers.

UNLABELLED: Lower leg ulcers are characterized by a chronic and recurrent course, being considered as a difficult therapeutic problem. Based on epidemiological data chronic ulcers concern 0.2 to 2% of the Western European population. The above-mentioned problem affects women more often than men, and increases with age. Treatment and recurrence prevention methods remain under discussion and research. The aim of the study was to evaluate the early surgical treatment results of venous leg ulcers at the Department of Traumatology and Emergency Medicine, Medical University of Lublin. MATERIAL AND METHODS: We evaluated patients hospitalized at the Department of Traumatology and Emergency Medicine, Medical University of Lublin during the period between 2009-2014. Inclusion criteria were as follows: venous leg ulceration, full documentation. The study group comprised 62 patients subjected to treatment for leg ulcerations, including 35 women and 27 men, aged between 30 and 94 years. The treatment method included the excision of the ulcers with the deep fascia, and the implantation of the mesh graft (thickness of skin) directly into the exposed muscle. RESULTS: Amongst patients evaluated at discharge, the healing of the transplant was as follows: in case of 44 patients 90-100%, in 8 patients - 75-89%, in 5 patients 50-74% and in 5 patients less than 50%. The predominating bacteria collected from ulceration samples was Pseudomonas aeruginosa (32%) and Staphylococcus aureus (35%). CONCLUSIONS: The patient outcome shows that surgery is an effective method considering treatment of venous leg ulcers. Earlier qualification for this type of surgery will improve patient outcome.

Antiseptic with modern wound dressings in the treatment of venous leg ulcers: clinical and microbiological aspects.

OBJECTIVE: To assess the impact of a two-period treatment on the clinical condition, bacteriological changes and results of treatment of venous leg ulcers (VLU) using octenidine dihydrochloride. METHOD: Patients with a VLU were recruited and treated with octenidine dihydrochloride for one month, after which they were randomised and treated with hydrocolloids or foam dressings. The wounds were clinically assessed for the amount of necrotic tissue, granulation tissue, epithelialisation, amount of exudate and pain level. During the first period, bacterial colonisation and antimicrobial efficacy of octenidine dihydrochloride were also evaluated. In the second period the efficacy of treatment, time of treatment and healing rate were investigated. RESULTS: In the group of 50 VLU patients, all wounds (100%) improved after the first treatment period. No clinical signs of infection were observed. Statistically significant changes were observed in all the clinical parameters studied in the treated groups of VLU patients, including reduction of necrotic tissue, the amount of exudate and of pain, as well as increased granulation and epithelialisation. In the second period including treatment with the two dressings, no differences were observed in treatment efficacy, time of treatment or healing rate. CONCLUSION: As used in this study, octenidine dihydrochloride proved to be effective and useful, changing the clinical condition of VLU, preparing the wound for future treatment with modern dressings. High microbicidal activity of octenidine was observed, both against Gram-negative and Gram-positive bacteria isolated from the ulcers. Octenidine dihydrochloride caused an eradication of multiresistant strains (88%) as well as of bacteria qualified as alert-pathogens (100%) in the treated wounds after four weeks. However, no differences in the effects, time or rate of healing of VLU with two dressings were found in the second period. No side effects or significant local intolerance reactions used for treatment were observed.