Effectiveness of Epidermal Growth Factor Loaded Carboxymethylcellulose (EGF-CMC) Hydrogel in Biofilm Formation in Wounds of Diabetic Patients: A Randomized Clinical Trial.

Diabetic patients frequently develop wounds, which can be colonized by bacteria, mainly Staphylococcus aureus and Pseudomonas aeruginosa, with the ability to form biofilms. This study aimed to evaluate the colonization and biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa in chronic wounds of diabetic patients treated with a bioactive dressing (EGF-CMC), which consisted of a 2% carboxymethylcellulose (CMC) hydrogel loaded with epidermal growth factor (EGF). This randomized clinical trial was conducted with 25 participants: 14 treated with EGF-CMC hydrogel and 11 treated with CMC hydrogel for 12 weeks. Participants with type 2 diabetes mellitus were selected. All had diabetic foot ulcers or chronic venous ulcers. Swab collections were performed on weeks 1, 6, and 12. The laboratory analyses included the identification of strains, microbial quantification, virulence gene investigation, and the evaluation of biofilm formation. In total, 13 S. aureus strains and 15 P. aeruginosa strains were isolated. There were no statistically significant differences regarding bacterial loads and virulence genes. However, EGF-CMC-hydrogel-treated wounds were colonized by strains with lower biofilm formation abilities. The probability of isolating biofilm-producing strains from CMC-hydrogel-treated wounds was 83% greater than the probability of isolating biofilm-producing strains from EGF-CMC-treated wounds.

Cicatrização de feridas diabéticas com fator de crescimento epidérmico: revisão integrativa / Healing of diabetic wounds with epidemic growth factor: integrative review / Curación de heridas diabéticas con factor de crecimiento epidérmico: revisión integrativa

Objetivo: Analisar as produções científicas sobre a efetividade do Fator de crescimento epitelial recombinante humano na cicatrização de feridas diabéticas. Métodos: Trata-se de uma revisão sistemática da literatura, a busca foi realizada nas bases de dados: Pubmed; Scopus e Lilacs. Resultados: Foram selecionados 21 artigos, sendo a maioria estudos experimentais (48%). A cicatrização completa de lesões tratadas com Fator de crescimento epitelial recombinante humano foi relatada por 17 artigos (81%). O aumento do tecido de granulação foi relatado em nove publicações (43%). Da mesma maneira, a diminuição da área da lesão foi descrita em dois artigos incluídos (10%). Duas publicações descrevem a diminuição do número de amputações e do estresse oxidativo e 62% dos artigos abordaram eventos adversos associados ao uso do produto (13/21), dos quais foram prioritários a ocorrência de tremores, dor local, calafrios, náuseas, infecção superficial, sensação de queimação e hematomas, considerados eventos adversos leves. Apenas um estudo apresentou a ocorrência de dor no peito como evento adverso grave. Conclusão: O fator de crescimento epitelial recombinante humano é indicado para uso tópico no tratamento de feridas diabéticas, evidenciando boa eficácia, porém mais estudos clínicos devem ser desenvolvidos. (AU)

Objective: To analyse the scientific studies of Human recombinant epithelial growth factor for the healing of diabetic wounds. Methods: A thorough review of the literature was performed in the following databases: PubMed, Scopus and LILACS. Results: 21 articles were selected, most studies were experimental (48%). Complete healing of Human recombinant epithelial growth factor-treated lesions has been reported by 17 articles (81%). Increased granulation tissue has been reported in nine publications (43%). Similarly, the reduction of the lesion area was described in two included articles (10%). Two publication describes the decrease in the number of amputations and oxidative stress and 62% of the articles addressed adverse events associated with the use of the product (13/21), of which the occurrence of tremors, local pain, chills, nausea, superficial infection, burning sensation and bruising were considered priority, considered adverse events light. Only one study showed chest pain as a serious adverse event. Conclusion: Although Human recombinant epithelial growth factor is indicated for topical use in the treatment of diabetic wounds and demonstrates good efficacy, more clinical studies should be developed. (AU)

Objetivo: Analizar la producción científica sobre la efectividad de Factor de crecimiento epitelial humano recombinante en la curación de heridas diabéticas. Métodos: Esta es una revisión sistemática de la literatura, la búsqueda se realizó en las bases de datos: Pubmed; Scopus y lilas. Resultados: Se seleccionaron 21 artículos. La mayoría de los estudios fueron experimentales (48%). 17 artículos informaron sobre la curación completa de lesiones tratadas con factor de crecimiento epitelial humano recombinante (81%). El aumento en el tejido de granulación se informó en nueve publicaciones (43%). Asimismo, se utilizó una reducción en el área de la lesión en dos artículos incluidos (10%). Dos publicaciones describen una disminución en el número de amputaciones y estrés oxidativo y el 62% de los artículos abordaron eventos adversos asociados con el uso del producto (13/21), que son las prioridades prioritarias en la aparición de temblores, dolor local, escalofríos, náuseas, infección superficial, sensación de ardor y hematomas, reflejos de eventos adversos leves. Solo un estudio muestra la aparición de dolor torácico como un evento adverso grave. Conclusión: Factor de crecimiento epitelial humano recombinante está indicado para uso tópico en el tratamiento de heridas diabéticas, mostrando buena eficacia, pero se deben desarrollar más estudios clínicos. (AU)

rhEGF-Loaded Hydrogel in the Treatment of Chronic Wounds in Patients with Diabetes: Clinical Cases.

The aim of the study was to evaluate the healing process of chronic wounds treated with carboxymethylcellulose loaded with recombinant human epidermal growth factor in patients with diabetes. The case series consisted of 10 patients treated at the university hospital for 12 weeks. Data were analyzed using SPSS version 22.0. according to the intention to treat the principle, without the loss or exclusion of the participants. The sample consisted of 70% (7/10) males with a mean age of 61.9 years (±9.4); all (100%) had diabetes mellitus and 70% (7/10) had systolic hypertension associated with diabetes mellitus. Sixty percent (6/10) presented lesions of diabetic etiology and 40% (4/10) presented lesions of venous etiology; 70% (7/10) had had lesions for less than 5 years. The mean glycated hemoglobin was 7.8% (±2.7%), while the mean ankle-arm index (AAI) was 0.94 (±0.21). The mean initial area of all wounds was 13.4 cm², and the mean final area was 7.8 cm2, with a reduction rate of 28.9% over the 12 weeks of treatment. The reduction rate of diabetic ulcers was higher (33.4%) than that of venous ulcers (22.1%). Regarding the type of tissue, there was an increase in granulation and epithelialization, and a decrease in slough and the amount of exudate that were statistically significant (p = 0.021). No participant had severe or local adverse events during the study period. Epidermal growth factor was effective in the treatment of chronic wounds, especially diabetic ulcers, resulting in the reduction of the wound area and the improvement of tissue and exudate quality.

Effectiveness of a synthetic human recombinant epidermal growth factor in diabetic patients wound healing: Pilot, double-blind, randomized clinical controlled trial.

To investigate whether the addition of human recombinant epidermal growth factor (h-EGF) to 2% carboxymethyl cellulose gel is more effective in diabetic wound healing than standard treatment, a pilot, double-blind, randomized and controlled clinical trial with therapeutic intervention was performed at a university hospital. The sample consisted of 25 patients (14 in the intervention group that used rh-EGF and 11 in the control group that used 2% carboxymethyl cellulose gel). Data were tabulated in SPSS and analysed by intention to treat, without loss or exclusion of participants. Twenty-five subjects participated with a mean age of 60.6 years, a predominance of males in both groups and 100% prevalence of type-2 diabetes. Within 12 weeks, complete wound healing occurred in three ulcers in the intervention group versus one ulcer in the control group. The percent reduction in the wound area was significantly higher in the intervention group than in the control group (p = 0.049). Concerning the types of tissue, an increase in granulation and epithelial tissue and a reduction in exudate levels were observed in both groups. Decreased slough occurred only in the intervention group. No participant experienced serious or local adverse events during the study period. This study shows that h-EGF is effective, with a statistically significant reduction in wound area, improvement of tissue quality, and safe treatment of chronic wounds. In addition, this study demonstrated that blinding of participants during research using h-EGF is feasible.

Tratamento de úlceras diabéticas com fator de crescimento epidérmico: relatos de caso / Treatment of diabetic ulcers with epidermal growth factor: case reports

Objetiva-se descrever o processo de cicatrização de pacientes com úlceras diabéticas tratadas com fator de crescimento epidérmico recombinante humano (rhEGF), e a colonização por Staphylococcus aureus e Pseudomonas aeruginosa. Estudo de casos de pacientes com úlceras diabéticas tratadas com rhEGF acompanhados ambulatorialmente em um hospital universitário. A coleta de dados ocorreu entre abril e agosto de 2017, com a obtenção de características clínicas, incluindo mensuração das áreas e registros fotográficos das lesões, bem como, coleta de material biológico por swab. A análise de dados foi feita por estatística descritiva. O cálculo da taxa apontou 100% de cicatrização no paciente 1 e 30% no paciente 2. Em relação ao tecido presente no leito da ferida, nota-se um aumento do tecido de granulação e epitelização e uma diminuição do tecido de esfacelo. Quanto ao exsudato, houve uma redução na quantidade presente na ferida ao fim do estudo. Não foram observados sinais clínicos de infecção nas feridas, os resultados das análises microbiológicas indicaram que a colonização microbiana por S. aureus e P. aeruginosa manteve-se no paciente 1 e foi minimizada no paciente 2. Concluise que a aplicação do rhEGF foi favorável na cicatrização de úlceras diabéticas e no controle microbiológico

The aim is to describe the healing process of patients with diabetic ulcers treated with recombinant human epidermal growth factor (rhEGF), and colonization by Staphylococcus aureus and Pseudomonas aeruginosa. Case study of patients with diabetic ulcers treated with rhEGF with outpatients in a university hospital. Data collection took place between April and August 2017, obtaining clinical characteristics, including measurement of areas and photographic records of the lesions, as well as collection of biological material by swab. The data analysis was done by descriptive statistics. The calculation of the rate indicated 100% healing in patient 1 and 30% in patient 2. In relation to the tissue present in the wound bed, there is an increase of granulation tissue and epithelization and a decrease of the shedding tissue. As for the exudate, there was reduction in the amount present in the wound at the end of the study. No clinical signs of infection were observed in the wounds. The results of the microbiological analyzes indicated that microbial colonization by S. aureus and P. aeruginosa was maintained in patient 1 and was minimized in patient 2. It concluded that the application of rhEGF was favorable in cicatrization of diabetic ulcers and in microbiological control

Molecular characterization of multidrug-resistant (MDR) Pseudomonas aeruginosa isolated in a burn center.

OBJECTIVE: The aim of this study was to characterize molecularly multidrug-resistant (MDR) Pseudomonas aeruginosa isolates collected from burn center (BC) patients and environment in a hospital localized in Rio de Janeiro city, RJ, Brazil. METHODS: Thirty-five P. aeruginosa isolates were studied. The antimicrobial resistance was tested by disk diffusion method as recommended by CLSI. The assessment of virulence (exoS and exoU) and resistance (blaPER-1, blaCTX-M, blaOXA-10, blaGES-1, blaVIM, blaIMP, blaSPM-1, blaKPC, blaNDM and blaSIM) genes were achieved through PCR and biofilm forming capacity was determined using a microtiter plates based-assay, as described previously. Genotyping was performed using Multilocus sequence typing (MLST). RESULTS: High rate of P. aeruginosa (71.4%; 25/35) were classified as MDR, of them 64% (16/25) were related to clone A, the most prevalent clone found in the BC studied. A total of eight carbapenems resistant isolates were detected; three belonging to clone A and five carrying the exoU virulence gene. In addition, clone A isolates were also biofilm producers. Two new sequence types (ST) were detected in this study: ST2236, grouped in to clone A; and ST2237, classified in the different clones, displaying carbapenem resistance and exoU virulence gene. CONCLUSION: The high prevalence of biofilm producers and multiresistant P. aeruginosa isolates in BC indicates that prevention programs need to be implemented to avoid infection in highly susceptible patients.

Balneotherapy is a potential risk factor for Pseudomonas aeruginosa colonization

ABSTRACT The practice of immersion in burn patient has been abandoned in many parts of the world but in Brazil it is still common. The aim of this study was to ascertain if balneotherapy is a risk factor for Pseudomonas aeruginosa colonization in thermally injured patients. Eighteen patients from a Burn Center were studied for 14 weeks for Pseudomonas aeruginosa. Samples were collected by swabbing the exudate of wounds, before and after giving bath to the patients and from balneotherapy table. Pulsed-field gel electrophoresis was used to determine bacterial genetic relatedness. Thirty-seven P. aeruginosa isolates were detected from 292 swabs collected from patients' burn surface area and from the balneotherapy table. Profile analysis of P. aeruginosa DNA fragmentation showed 10 clones among the 37 strains analyzed. Type A is the most prevalent clone, with 23 strains distributed into eight subtypes. These were present in the swabs collected, before and after the patients' bath, from the surface of the bath table, suggesting that there was cross-contamination between the patients in different ways. This work demonstrates that balneotherapy is a risk factor in the Burn Center studied, because the same clone was found among P. aeruginosa isolates collected at various points and times.

RESUMO A prática de balneotarapia em paciente queimado foi abandonada em muitas partes do mundo, mas no Brasil ainda é comum. O objetivo deste estudo foi verificar se a balneoterapia é um fator de risco para a colonização por Pseudomonas aeruginosa em pacientes queimados. Dezoito pacientes internados em um Centro de Queimadura (CQ) foram acompanhados por 14 semanas. Amostras foram coletadas do exsudato de feridas, antes e depois do banho dos pacientes e também da mesa onde a balneoterapia foi realizada. A relação genética entre as cepas de P. aeruginosa foi determinada pela electroforese em gel de campo pulsado. Trinta e sete cepas foram detectadas a partir de 292 swabs coletados de área de superfície das feridas dos pacientes e da mesa de balneoterapia. Análise de fragmentação do DNA das 37 P. aeruginosa mostrou a existência de 10 clones. O tipo A foi o clone mais prevalente, com 23 cepas distribuídas em oito subtipos. Estas estavam presentes nas lesões dos pacientes antes e após o banho e na mesa onde o banho foi realizado, sugerindo contaminação cruzada inter e intra-pacientes e pacientes e mesa de banho. Este trabalho mostra que a balneoterapia é um fator de risco para colonização por P. aeruginosa, no CQ estudado, pois um mesmo clone da bactéria foi encontrado nos isolados coletados em vários pontos e épocas diferentes.