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.

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.

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.

[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.

Bastonetes Gram-negativos em úlceras venosas e implicações para o atendimento de enfermagem na atenção primári / Gram-negative rods in venous ulcers and implications for primary care nursing care / Bacilos Gram-negativos en úlceras venosas, implicancias para la atención de enfermería en la atención primaria

Estudo transversal descritivo em pacientes com úlceras venosas de difícil cicatrização, cujos objetivos foram identificar a prevalência de bastonetes Gram-negativos (BGN) em úlceras venosas com sinais clínicos de infecção; analisar o perfil de suscetibilidade destes e detectar a produção de ESBL, AmpC e metalo-ß-lactamase. Nesta amostra, identificaram-se 69 pessoas. A coleta foi realizada mediante entrevista, exame clínico, registro fotográfico e swab das lesões. Os espécimes foram submetidos à avaliação laboratorial para análise microbiológica. Foram avaliadas 98 lesões, sendo isolados BGN em 74,5%. Prevaleceram P. aeruginosae Escherichia coli. Os micro-organismos foram sensíveis à maioria dos antimicrobianos. Em relação à resistência, destacaram-se tetraciclina e cefoxitina. ESBL não foi detectada, AmpC foi verificada em 37,5% no grupo CESP e a metalo-ß-lactamase em 8,0% das P. aeruginosa. O estudo indica a necessidade de vigilância microbiológica para os pacientes com úlceras venosas com processo cicatricial de difícil evolução.

A descriptive cross-sectional study in patients with hard-to-heal venous ulcers, whose objective is to identify the prevalence of Gram-negative rods (GNR) in venous ulcers presenting clinical signs of infection; analyze the susceptibility profile of such ulcers and detect ESBL, AmpC and metallo-ß-lactamase production. We identified 69 individuals. The samples were gathered by means of an interview, clinical exam, photographic record and a swab of the lesions. Specimens were submitted to laboratorial evaluation for microbiological analysis. A total of 98 lesions were evaluated, of which BGN presented in 74.5%. There was a prevalence of P. aeruginosa and Escherichia coli. The mircoorganisms were sensitive to most antimicrobials. In terms of resistance, tetracycline and cefoxitine were discarded. ESBL was not detected; AmpC was verified in 37.5% of the CESP group and metalo-ß-lactamase in 8.0% of P. aeruginosa. Our study points to the need for microbiological vigilance of patients with hard-to-heal venous ulcers.

Estudio transversal descriptivo en pacientes con úlceras venosas de difícil cicatrización, objetivando identificar la prevalencia de bacilos Gram-negativos (BGN) en ulceras venosas con signos clínicos de infección; analizar su perfil de susceptibilidad y detectar la producción de ESBL, AmpC y metalo-ß-lactamasa. Fueron identificadas 69 personas. Datos recolectados mediante entrevista, examen clínico, registro fotográfico y swab de lesiones. Los especímenes fueron sometidos a evaluación laboratorial para análisis microbiológico. Fueron evaluadas 98 lesiones, aislándose BGN en 74,5%. Prevalecieron P. aeruginosay Escherichia coli. Los microorganismos fueron sensibles a la mayoría de antimicrobianos. Respecto a resistencia, se destacó la misma respecto de tetraciclina y cefoxitina. No se detectó ESBL, se verificó AmpC en 37,5% en el grupo CESP y la metalo-ß-lactamasa en 8,0% de las P. aeruginosa. El estudio indica necesidad de vigilancia microbiológica para pacientes con úlceras venosas con proceso cicatricial de difícil evolución.

The influence of patient and wound variables on healing of venous leg ulcers in a randomized controlled trial of growth-arrested allogeneic keratinocytes and fibroblasts.

OBJECTIVE: To examine patient and wound variables presumed to influence healing outcomes in the context of therapeutic trials for chronic venous leg ulcers. METHODS: This double-blind, vehicle-controlled study was conducted with randomized assignment to one of four cell therapy dose groups (n = 46, 43, 44, 45) or vehicle control (n = 50). A 2-week run-in period was used to exclude rapid healers and those with infection or uncontrolled edema. This was a multicenter (ambulatory, private, hospital-based and university-based practices, and wound care centers in North America) study. Adults ≥ 18 years old with chronic venous insufficiency associated with an uninfected venous leg ulcer (2-12 cm(2) area, 6-104 weeks' duration) were included in the study. Excluded were pregnant or lactating women, wounds with exposed muscle, tendon or bone, patients unable to tolerate compression bandages, or patients who had exclusionary medical conditions or exposure to certain products. Exclusion during run-in included patients with infection, uncontrolled severe edema or with healing rates ≥ 0.349 cm/2 wk. Screen fail rate was 37% (134/362), and the withdrawal rate was~10% (23 of 228). Growth-arrested neonatal dermal fibroblasts and keratinocytes were delivered via pump spray in a fibrin sealant-based matrix, plus a foam dressing and four-layer compression bandaging. Treatment continued for 12 weeks or until healed, whichever occurred first. Patient demographic and wound-related variables were evaluated for influence on complete wound healing in all patients, as well as the subsets of treated and control patients. RESULTS: Wound duration (P = .004) and the presence of specific quantities of certain bacterial species (P < .001) affected healing in the vehicle group, while healing in the cell-treated groups was influenced by wound duration (P = .012), wound area (P = .026), wound location (P = .011), and specific quantities of certain bacterial species (P = .002). Age, sex, race, diabetes, HbA1C, peripheral neuropathy, and serum prealbumin did not significantly affect healing. Body mass index was positively associated with healing in cell-treated patients. CONCLUSIONS: Wound duration is a quantifiable surrogate for one or more undefined variables that can have a profound negative effect on venous leg ulcer healing. Although cell therapy overcame barriers to healing, the only specific barrier identified was the presence of certain bacterial species. Interventional trials of potentially effective new therapies can be most informative when patients with suspected barriers to healing are included. The specific measurement of candidate barriers such as microbial pathogens, wound inflammatory state, and fibroblast function should be considered in future randomized trials to improve our understanding of the basis for chronicity.

Influence of hydrogencalcium salts of oxidized cellulose on MMP-2, MMP-9 and TNF-α production and wound healing in non-healing wounds.

Levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-α (TNF-α) may influence wound healing and wound closure in non-healing wounds. The aim of the study was to test the hypothesis that hydrogencalcium salts of oxidized cellulose change the production of matrix metalloproteinases (MMPs) and TNF-α, wound size and number of bacterial strains in non-healing wounds. We analyzed MMP-2, MMP-9 and TNF-α in the wound fluid from 20 patients by ELISA every fourteen days over six weeks. Wound size, pain, wound closure and bacterial strains in the wound were also investigated. The wound size was reduced in 14 patients and pain in 16 patients. Bacterial contamination of the wound decreased significantly after treatment. The level of MMP-2 correlated with TNF-α production. The level of MMP-9 was unchanged during the healing period. We conclude that hydrogencalcium salts of oxidized cellulose have a favorable effect on the reduction of bacterial contamination, wound size and pain.

Prevalence of resistance phenotypes in Staphylococcus aureus and coagulase-negative isolates of venous ulcers of primary healthcare patients / Prevalência de fenótipos de resistência em Staphylococcus aureus e coagulase negativos isolados de úlceras venosas de pessoas atendidas na atenção primária

INTRODUCTION: In venous ulcers, the presence of Staphylococcus aureus and coagulase-negative staphylococcus resistance phenotypes can aggravate and limit the choices for treatment. METHODS: Staphylococcus isolated from 69 patients (98 ulcers) between October of 2009 and October of 2010 were tested. The macrolide, lincosamide, streptogramin B (MLS B) group resistance phenotype detection was performed using the D-test. Isolates resistant to cefoxitin and/or oxacillin (disk-diffusion) were subjected to the confirmatory test to detect minimum inhibitory concentration (MIC), using oxacillin strips (E-test®). RESULTS: The prevalence of S. aureus was 83%, and 15% of coagulase-negative staphylococcus (CoNS). In addition were detected 28% of methicillin-resistant Staphylococcus aureus (MRSA) and 47% of methicillin-resistant coagulase-negative staphylococcus (MRCoNS). Among the S. aureus, 69.6% were resistant to erythromycin, 69.6% to clindamycin, 69.6% to gentamicin, and 100% to ciprofloxacin. Considering the MRSA, 74% were highly resistant to oxacillin, MIC ≥ 256µg/mL, and the MLS Bc constitutive resistance predominated in 65.2%. Among the 20 isolates sensitive to clindamycin, 12 presented an inducible MLS B phenotype. Of the MRCoNS, 71.4%were resistant to erythromycin, ciprofloxacin and gentamicin. Considering the isolates positive for β-lactamases, the MIC breakpoint was between 0.5 and 2µg/mL. CONCLUSIONS: The results point to a high occurrence of multi-drug resistant bacteria in venous ulcers in primary healthcare patients, thus evidencing the need for preventive measures to avoid outbreaks caused by multi-drug resistant pathogens, and the importance of healthcare professionals being able to identifying colonized versus infected venous ulcers as an essential criteria to implementing systemic antibacterial therapy.

INTRODUÇÃO: Em úlceras venosas, a presença de Staphylococcus aureus e coagulase negativo com fenótipos de resistência pode constituir fator agravante e limita as opções terapêuticas. MÉTODOS: Foram avaliados estafilococos isolados de 69 pacientes, representando 98 úlceras no período de outubro de 2009 a outubro de 2010. A detecção fenotípica da resistência ao grupo macrolide, lincosamide, streptogramin B (MLS B) foi realizada pelo D-test. Isolados resistentes a cefoxitina e/ou oxacilina (disco-difusão) foram submetidos ao teste confirmatório para detecção da minimum inhibitory concentration (MIC), empregando fitas de oxacilina (E-test®). RESULTADOS: A prevalência de S. aureus foi de 83% e de 15% de coagulase-negative staphylococcus (CoNS). Identificou-se 28% de methicillin-resistant Staphylococcus aureus (MRSA) e 47% de methicillin-resistant coagulase-negative staphylococcus (MRCoNS). Entre o S. aureus, 69,6% apresentaram resistência a eritromicina, 69,6% a clindamicina, 69,6% a gentamicina e 100% a ciprofloxacina. Setenta e quatro por cento dos MRSA apresentaram elevado nível de resistência a oxacilina, MIC ≥ 256µg/mL, e em 65,2% predominou a resistência constitutiva MLS Bc. Dos 20 isolados sensíveis a clindamicina, 12 apresentaram fenótipo MLS B induzível. Um total de 71,4% dos MRCoNS apresentaram resistência a eritromicina, ciprofloxacina e gentamicina. Dos isolados positivos para a enzima β-lactamases, as MIC tiveram breakpoint entre 0,5 a 2µg/mL. CONCLUSÕES: Os resultados sinalizam elevada ocorrência de bactérias multirresistentes em úlceras venosas de pacientes recebendo atenção primária, evidenciando a necessidade de medidas preventivas que evitem surtos causados por patógenos resistentes a múltiplas drogas e a importância dos profissionais em discernir infecção de colonização em úlcera venosa, critério fundamental na indicação antibioticoterapia sistêmica.

Laser irradiation effect on Staphylococcus aureus and Pseudomonas aeruginosa biofilms isolated from venous leg ulcer.

Chronic wounds, including diabetic foot ulcers, pressure ulcers and venous leg ulcers, represent a significant cause of morbidity in developed countries, predominantly in older patients. The aetiology of these wounds is probably multifactorial, but the role of bacteria in their pathogenesis is still unclear. Moreover, the presence of bacterial biofilms has been considered an important factor responsible for wounds chronicity. We aimed to investigate the laser action as a possible biofilm eradicating strategy, in order to attempt an additional treatment to antibiotic therapy to improve wound healing. In this work, the effect of near-infrared (NIR) laser was evaluated on mono and polymicrobial biofilms produced by two pathogenic bacterial strains, Staphylococcus aureus PECHA10 and Pseudomonas aeruginosa PECHA9, both isolated from a chronic venous leg ulcer. Laser effect was assessed by biomass measurement, colony forming unit count and cell viability assay. It was shown that the laser treatment has not affected the biofilms biomass neither the cell viability, although a small disruptive action was observed in the structure of all biofilms tested. A reduction on cell growth was observed in S. aureus and in polymicrobial biofilms. This work represents an initial in vitro approach to study the influence of NIR laser treatment on bacterial biofilms in order to explain its potentially advantageous effects in the healing process of chronic infected wounds.

Success rate of split-thickness skin grafting of chronic venous leg ulcers depends on the presence of Pseudomonas aeruginosa: a retrospective study.

The last years of research have proposed that bacteria might be involved in and contribute to the lack of healing of chronic wounds. Especially it seems that Pseudomonas aeruginosa play a crucial role in the healing. At Copenhagen Wound Healing Centre it was for many years clinical suspected that once chronic venous leg ulcers were colonized (weeks or months preoperatively) by P. aeruginosa, the success rate of skin grafting deteriorated despite aggressive treatment. To investigate this, a retrospective study was performed on the clinical outcome of 82 consecutive patients with chronic venous leg ulcers on 91 extremities, from the 1(st) of March 2005 until the 31(st) of August 2006. This was achieved by analysing the microbiology, demographic data, smoking and drinking habits, diabetes, renal impairment, co-morbidities, approximated size and age of the wounds, immunosuppressive treatment and complicating factors on the clinical outcome of each patient. The results were evaluated using a Student T-test for continuous parameters, chi-square test for categorical parameters and a logistic regression analysis to predict healing after 12 weeks. The analysis revealed that only 33,3% of ulcers with P. aeruginosa, isolated at least once from 12 weeks prior, to or during surgery, were healed (98% or more) by week 12 follow-up, while 73,1% of ulcers without P. aeruginosa were so by the same time (p = 0.001). Smoking also significantly suppressed the outcome at the 12-week follow-up. Subsequently, a logistic regression analysis was carried out leaving P. aeruginosa as the only predictor left in the model (p = 0.001). This study supports our hypothesis that P. aeruginosa in chronic venous leg ulcers, despite treatment, has considerable impact on partial take or rejection of split-thickness skin grafts.

Quantitative analysis of the cellular inflammatory response against biofilm bacteria in chronic wounds.

Chronic wounds are an important problem worldwide. These wounds are characterized by a persistent inflammatory stage associated with excessive accumulation and elevated cell activity of neutrophils, suggesting that there must be a persistent stimulus that attracts and recruits neutrophils to the wound. One such stimulus might be the presence of bacterial biofilms in chronic wounds. In the present study, biopsy specimens from chronic venous leg ulcers were investigated for the detection of bacteria using peptide nucleic acid-based fluorescence in situ hybridization (PNA-FISH) and confocal laser scanning microscopy. The bacteria in the wounds were often situated in large aggregates. To obtain a measure of the cellular inflammatory response against the bacteria in the chronic wounds, the amount of neutrophils accumulated at the site of infection was evaluated through differential neutrophil counting on the tissue sections from wounds containing either Pseudomonas aeruginosa or Staphylococcus aureus. The P. aeruginosa-containing wounds had significantly higher numbers of neutrophils accumulated compared with the S. aureus-containing wounds. These results are discussed in relation to the hypothesis that the presence of P. aeruginosa biofilms in chronic wounds may be one of the main factors leading to a persistent inflammatory response and impaired wound healing.

Nonrandom distribution of Pseudomonas aeruginosa and Staphylococcus aureus in chronic wounds.

The spatial organization of Pseudomonas aeruginosa and Staphylococcus aureus in chronic wounds was investigated in the present study. Wound biopsy specimens were obtained from patients diagnosed as having chronic venous leg ulcers, and bacterial aggregates in these wounds were detected and located by the use of peptide nucleic acid-based fluorescence in situ hybridization and confocal laser scanning microscopy (CLSM). We acquired CLSM images of multiple regions in multiple sections cut from five wounds containing P. aeruginosa and five wounds containing S. aureus and measured the distance of the bacterial aggregates to the wound surface. The distance of the P. aeruginosa aggregates to the wound surface was significantly greater than that of the S. aureus aggregates, suggesting that the distribution of the bacteria in the chronic wounds was nonrandom. The results are discussed in relation to our recent finding that swab culturing techniques may underestimate the presence of P. aeruginosa in chronic wounds and in relation to the hypothesis that P. aeruginosa bacteria located in the deeper regions of chronic wounds may play an important role in keeping the wounds arrested in a stage dominated by inflammatory processes.

Epidemiologic genotyping of methicillin-resistant Staphylococcus aureus (MRSA) by pulsed-field gel electrophoresis (PFGE).

Staphylococcus aureus has long been recognized as one of the leading cause of hospital infections all over the world. Increased frequency of methicillin-resistant Staphylococcus aureus (MRSA) in hospitalized patients and possibility of vancomycin resistance requires rapid and reliable characterization of isolates and control of MRSA spread in hospitals. Typing of isolates helps to understand pathogenesis and route of the hospital pathogen spread. In this study, in the analysis of an outbreak of MRSA infections in one surgical ward, we used pulsed-field gel electrophoresis (PFGE) as a method of typing. PFGE revealed one epidemic strain type A in 13 out of 16 patients, and another two types (type B in two patients and type C in one patient). Discussing the typing results in the ward has changed the admission policy of patients with infected vascular ulcers who were then cured as outpatients, and admitted for surgery after that. This policy resulted with the stopping of the outbreak; during next 2.5 year there was no further MRSA outbreak in the ward. PFGE also showed subtypes which enabled the insight into dynamics of MRSA strain changes during the outbreak. PFGE could be recommended as a screening method in the MRSA outbreak analysis. Because of it's high discriminatory power still remains the gold standard for MRSA typing.

Why chronic wounds will not heal: a novel hypothesis.

The present paper presents a hypothesis aimed at explaining why venous leg ulcers, pressure ulcers, and diabetic foot ulcers develop into a chronic state. We propose that the lack of proper wound healing is at least in part caused by inefficient eradication of infecting, opportunistic pathogens, a situation reminiscent of chronic Pseudomonas aeruginosa infections found in patients suffering from cystic fibrosis (CF). We have analyzed sections from chronic wounds by fluorescence in situ hybridization and found distinct microcolonies--the basal structures of bacterial biofilms. Several researchers have previously reported that another important hallmark of biofilm formation is development of increased tolerance to various antimicrobial measures and treatments. Furthermore, the immune response to infecting bacteria in the cystic fibrosis lung is dominated by polymorphonuclear neutrophils (PMNs), and we have recently shown that in vitro biofilms of P. aeruginosa produce a shielding mechanism that offers protection from the phagocytic activity of PMNs. We hypothesize that the presence of P. aeruginosa in biofilms, and the lack of concomitant elimination by attended PMNs, are the main causes of inefficient eradication by antibiotic treatment and antimicrobial activity of the innate immune system, respectively.

Interleukin-6 concentrations in wound fluids rather than serological markers are useful in assessing bacterial triggers of ulcer inflammation.

Bacterial pathogenicity, microbial load and diversity are decisive for outcome and therapy of non healing ulcers. However, until now, no routine laboratory parameter is available to assess the inflammatory level caused by chronic wound infections. We thus investigated the usefulness of levels of interleukin (IL)-6 and tumour necrosis factor alpha (TNFalpha) in wound fluids for assessing ulcer inflammation in the presence or absence of microbial triggers. In addition, the predictive values of local cytokine analyses were compared with those of C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) because serological markers are normally used to underline the suspicion of wound infections. The present data from chronic arterial and venous ulcers (n = 45) clearly show that mixed bacterial infections increased IL-6 and TNFalpha concentrations in wound fluids when compared with ulcers with a monomicrobial infection (P < 0.01 and P < 0.05, respectively). IL-6 was also significantly elevated when a high bacterial load [versus <10(5) colony-forming units (cfu)/ml: P = 0.04] or an infection with Pseudomonas was observed (versus isolation of non Pseudomonas strains: P = 0.05). Although distinct proinflammatory triggers may interfere with regard to cytokine levels, sensitivity and specificity were significant in predicting bacterial risk factors, particularly for IL-6 at a designated cut-off of 125 pg/ml (sensitivity and specificity for predicting a mixed infection: 70% and 64%, for predicting a bacterial load of >10(5) cfu/ml: 62% and 57% and for predicting an infection with Pseudomonas: 90% and 57%). In contrast to local cytokine levels, the serological markers CRP and LBP were not associated with the presence of any of the investigated bacterial triggers. Focusing on the aim of the study, IL-6 analysed in wound washouts seems to be a useful diagnostic marker for a sensitive and specific assessment of ulcers inflammation with regard to bacterial triggers.

Antimicrobial therapy for skin infections.

The most common skin infections are caused by Staphylococcus aureus, group A streptococci (Streptococcus pyogenes), or the normal skin flora. An antistaphylococcal oral antibiotic is the preferred treatment for nonbullous and bullous impetigo, and a therapeutic agent that is effective against both S aureus and streptococci is appropriate for most cases of cellulitis. For furuncles, carbuncles, cutaneous abscesses, and inflamed epidermal cysts, the most important therapy is incision and drainage, and in most cases there is no need for antimicrobial therapy. Patients with venous ulcers and atopic eczema do not benefit from systemic antimicrobial therapy unless obvious infection is present, as indicated by clinical features such as fever, cellulitis, and lymphangitis.

A prospective study of the microbiology of chronic venous leg ulcers to reevaluate the clinical predictive value of tissue biopsies and swabs.

This study determined whether comprehensive microbiological analysis offered real predictive value in terms of healing outcome, and assessed the clinical usefulness of surface swabs vs. tissue biopsies for clinically noninfected leg wounds. The wound microflora of 70 patients with chronic venous leg ulcers was quantified after sampling by swabbing and biopsy. A highly significant association between wound surface area at 4 weeks and eventual healing at 6 months was found (p<0.001), although initial wound size, sex, height, and weight were not significant predictors of outcome (p>0.1). A significant association between healing and bacterial diversity in the wound as assessed by swab (p=0.023) was demonstrated. Furthermore, the bacterial density of wound surface area by swab (CFU/mL; p=0.018) or biopsy (CFU/g tissue; p=0.038) were shown to be independent predictors of nonhealing. Logistic regression showed that microbiological analysis of biopsies provided no additional prognostic information when compared with analysis of the surface microflora (p=0.27). Hence, if biopsies do not contribute significantly to patient management, their use should be discouraged in clinically noninfected wounds. Furthermore, independent predictors of healing, such as wound surface microbial diversity and density, could identify patients likely to have an unfavorable outcome and to whom resources should be targeted.

[Surgical technologies in the treatment of varicose veins of the lower extremities complicated with trophic ulcer].

Results of an open randomized study of staged treatment of 94 patients suffering from varicose veins of the lower extremities with open infected trophic ulcers of the shank were analyzed. All the patients were divided into 3 groups depending on the treatment variant. Based on this study, clinical efficacy of early correction of upper vertical venous-venous reflux is substantiated. Efficacy of CO(2) laser application for sanation of trophic venous ulcers and practical importance of their auto-venous plastic reconstruction are demonstrated. Thus, up-to-date technologies provide differential treatment in patients with trophic venous ulcers.