Association of multidrug-resistant bacteria and clinical outcomes in patients with infected diabetic foot in a Peruvian hospital: A retrospective cohort analysis.

OBJECTIVE: To evaluate the association of multidrug-resistant bacteria (MDRB) and adverse clinical outcomes in patients with diabetic foot infection (DFI) in a Peruvian hospital. MATERIALS AND METHODS: This retrospective cohort study evaluated patients treated in the Diabetic Foot Unit of a General Hospital in Lima, Peru. MDRB was defined by resistance to more than two pharmacological groups across six clinically significant genera. The primary outcome was death due to DFI complications and/or major amputation. Other outcomes included minor amputation, hospitalization, and a hospital stay longer than 14 days. Relative risks were estimated using Poisson regression for all outcomes. RESULTS: The study included 192 DFI patients with a mean age of 59.9 years; 74% were males. A total of 80.8% exhibited MDRB. The primary outcome had an incidence rate of 23.2% and 5.4% in patients with and without MDRB, respectively (p = 0.01). After adjusting for sex, age, bone involvement, severe infection, ischemia, diabetes duration, and glycosylated hemoglobin, MDRB showed no association with the primary outcome (RR 3.29; 95% CI, 0.77-13.9), but did with hospitalization longer than 14 days (RR 1.43; 95% CI, 1.04-1.98). CONCLUSIONS: Our study found no association between MDRB and increased mortality and/or major amputation due to DFI complications, but did find a correlation with prolonged hospitalization. The high proportion of MDRB could limit the demonstration of the relationship. It is urgent to apply continuous evaluation of bacterial resistance, implement a rational plan for antibiotic use, and maintain biosafety to confront this threat.

Adjuvant effect of antimicrobial photodynamic therapy (aPDT) in the treatment of diabetic foot ulcers: A case series.

This study aimed to evaluate the clinical evolution of patients with diabetic foot ulcer treated with antimicrobial photodynamic therapy (aPDT) using the Bates-Jensen (BJ) scale. A total of 21 patients were monitored, with an average age of 58 years. Patients underwent the standard treatment protocol of the institution, supplemented with aPDT utilizing 0.01% methylene blue (MB) and laser irradiation (660 nm, 100 mW, 6 J per point). Following aPDT, the lesions were protected with hydrofiber dressings containing silver. The Bates-Jensen Scale was employed at pre-treatment and post-aPDT sessions to assess lesion progression. The results demonstrated a significant difference between pre- and post-treatment values in the overall BJ score. The use of MB in aPDT proved to be an effective, safe, well-tolerated treatment with high patient adherence and the potential for implementation in the care of diabetic foot conditions.

Increase in antibiotic resistance in diabetic foot infections among peruvian patients: a single-center cross-sectional study.

Background: Diabetic foot is one of the most significant complications in individuals with diabetes and is closely associated with lower limb amputation. The antibiotic susceptibility patterns of these bacterial isolates play a critical role in guiding effective treatment strategies We aimed to determine the most common bacterial agents causing diabetic foot infections in a tertiary-care hospital in Peru. Methods: Clinical and microbiological data were collected from 181 patients diagnosed with diabetic foot infections and positive microbiological culture results. All the samples were analyzed with the Vitek 2 compact system and the cut-off points were defined with the CLSI M100 guide. The data were segregated based on mono-microbial or poly-microbial cultures, bacterial types, and antibiotic susceptibility profiles. Results: A total of 32 bacterial species were identified, predominantly Gram-negative (63%). The most frequent bacterial agents isolated were Staphylococcus aureus (19.9%), Escherichia coli (12.2%), Pseudomonas aeruginosa (8.3%), and Proteus vulgaris (6.6%). These bacteria commonly exhibited resistance to Ampicillin, Ciprofloxacin, Levofloxacin, Trimethoprim-sulfamethoxazole, and Cefuroxime. E. coli showed the highest antibiotic resistance (19 antibiotics), while Gentamicin, Tobramycin, and Levofloxacin demonstrated the highest sensitivity against the most prevalent bacteria. Gram-negative bacteria also exhibited notable antibiotic-susceptibility to Meropenem, Piperacillin/tazobactam, and Amikacin. Regarding the presence of Extended-Spectrum Beta-Lactamase, 54 isolates tested positive, with 35 (64.8%) and 14 (42.4%) of these being S. aureus and E. coli. Conclusions: Bacterial agents causing diabetic foot infections pose a constant concern, particularly due to the increasing antibiotic resistance observed. This difficulty in treating the condition contributes to a higher risk of amputation and mortality. Further research on bacterial susceptibility is necessary to determine appropriate dosages for pharmacological treatment and to prevent the overuse of antibiotics.

Úlceras de pie diabético infectadas con bacterias multirresistentes a los antimicrobianos en pacientes venezolanos / Diabetic Foot Ulcers Infected with Bacteria Multiresistant to Antimicrobials in Venezuelan patients

Introducción: Las úlceras de pie diabético tienen una importante morbimortalidad, más aun, si están asociadas a bacterias multirresistentes a los antimicrobianos. Objetivo: Analizar las características de las úlceras de pie diabético infectadas con bacterias multirresistentes a los antimicrobianos. Métodos: Se realizó una investigación descriptiva, no experimental y transversal, en 87 pacientes con úlceras de pie diabético infectadas, atendidos en una consulta especializada del estado Zulia, Venezuela. Se realizó la anamnesis y exploración física, especialmente centrada en las características de las úlceras de pie diabético. Se obtuvieron muestras de tejido ulceroso para identificar las bacterias presentes y el antimicrobiano correspondiente. Resultados: Todos los pacientes tenían úlcera previa, con agudización de la infección (75,86 por ciento), rehospitalización (59,77 por ciento), amputación previa (36,78 por ciento), úlceras de pie diabético infectadas de larga duración (86,21 por ciento). El 95,40 por ciento recibieron antibióticos previos y 57,62 por ciento habían sido hospitalizados, la antigüedad de la enfermedad fue 16,17 ± 8,41 años y la HbA1c 8,87 ± 1,23. Las úlceras de pie diabético infectadas más frecuente fue neuroisquémica (71,26 por ciento). Predominó la flora monomicrobiana con un (62,07 por ciento) y bacterias gramnegativas (87,36 por ciento). El 79,3 por ciento presentaron bacterias multirresistentes a los antimicrobianos y el 20,69 por ciento panresistencia. Las bacterias multirresistentes fueron predominantemente gramnegativas, y para las grampositivas solo estuvo el Staphylococcus aureus. Conclusiones: Se presenció una alta frecuencia de úlceras de pie diabético infectadas con multirresistencia, predominantemente monomicrobianas y todas con resistencia a betalactámicos y fluoroquinolonas(AU)

Introduction: Diabetic foot ulcers have significant morbidity and mortality, even more so if they are associated with multi-resistant bacteria to antimicrobials. Objective: To analyze the characteristics of diabetic foot ulcers infected with bacteria multi-resistant to antimicrobials. Methods: A descriptive, non-experimental and cross-sectional investigation was carried out in 87 patients with infected diabetic foot ulcers. They were treated in a specialized clinic in Zulia state, Venezuela. Anamnesis and physical examination were performed, especially focused on the characteristics of diabetic foot ulcers. Ulcer tissue samples were obtained to identify the bacteria existing and the corresponding antimicrobial. Results: All the patients had previous ulcer, with exacerbation of the infection (75.86percent), rehospitalization (59.77percent), previous amputation (36.78percent), long-lasting infected diabetic foot ulcers (86.21percent). 95.40percent received previous antibiotics and 57.62percent had been hospitalized, the disease age was 16.17 ± 8.41 years and Hb A1c was 8.87 ± 1.23. The most frequent infected diabetic foot ulcers were neuroischemic (71.26percent). The monomicrobial flora (62.07percent) and gram-negative bacteria (87.36percent) predominated. 79.3percent had multi-resistant bacteria to antimicrobials and 20.69percent pan-resistance. Multi-resistant bacteria were predominantly gram-negative and for gram-positive only staphylococcus aureus. Conclusions: High frequency of multidrug-resistant infected diabetic foot ulcers was found, predominantly monomicrobial and all with resistance to beta-lactams and fluoroquinolones(AU)

Dressings and topical agents containing hyaluronic acid for chronic wound healing.

BACKGROUND: Hyaluronic acid is synthesised in plasma membranes and can be found in extracellular tissues. It has been suggested that the application of hyaluronic acid to chronic wounds may promote healing, and the mechanism may be due to its ability to maintain a moist wound environment which helps cell migration in the wound bed. OBJECTIVES: To evaluate the effects of hyaluronic acid (and its derivatives) on the healing of chronic wounds. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was February 2022. SELECTION CRITERIA: We included randomised controlled trials that compared the effects of hyaluronic acid (as a dressing or topical agent) with other dressings on the healing of pressure, venous, arterial, or mixed-aetiology ulcers and foot ulcers in people with diabetes. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 12 trials (13 articles) in a qualitative synthesis, and were able to combine data from four trials in a quantitative analysis. Overall, the included trials involved 1108 participants (mean age 69.60 years) presenting 178 pressure ulcers, 54 diabetic foot ulcers, and 896 leg ulcers. Sex was reported for 1022 participants (57.24% female). Pressure ulcers It is uncertain whether there is a difference in complete healing (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.58 to 2.35); change in ulcer size (mean difference (MD) 25.60, 95% CI 6.18 to 45.02); or adverse events (none reported) between platelet-rich growth factor (PRGF) + hyaluronic acid and PRGF because the certainty of evidence is very low (1 trial, 65 participants). It is also uncertain whether there is a difference in complete healing between lysine hyaluronate and sodium hyaluronate because the certainty of evidence is very low (RR 2.50, 95% CI 0.71 to 8.83; 1 trial, 14 ulcers from 10 participants). Foot ulcers in people with diabetes It is uncertain whether there is a difference in time to complete healing between hyaluronic acid and lyophilised collagen because the certainty of evidence is very low (MD 16.60, 95% CI 7.95 to 25.25; 1 study, 20 participants). It is uncertain whether there is a difference in complete ulcer healing (RR 2.20, 95% CI 0.97 to 4.97; 1 study, 34 participants) or change in ulcer size (MD -0.80, 95% CI -3.58 to 1.98; 1 study, 25 participants) between hyaluronic acid and conventional dressings because the certainty of evidence is very low. Leg ulcers We are uncertain whether there is a difference in complete wound healing (RR 0.98, 95% CI 0.26 to 3.76), percentage of adverse events (RR 0.79, 95% CI 0.22 to 2.80), pain (MD 2.10, 95% CI -5.81 to 10.01), or change in ulcer size (RR 2.11, 95% CI 0.92 to 4.82) between hyaluronic acid + hydrocolloid and hydrocolloid because the certainty of evidence is very low (1 study, 125 participants). It is uncertain whether there is a difference in change in ulcer size between hyaluronic acid and hydrocolloid because the certainty of evidence is very low (RR 1.02, 95% CI 0.84 to 1.25; 1 study, 143 participants). We are uncertain whether there is a difference in complete wound healing between hyaluronic acid and paraffin gauze because the certainty of evidence is very low (RR 2.00, 95% CI 0.21 to 19.23; 1 study, 24 ulcers from 17 participants). When compared with neutral vehicle, hyaluronic acid probably improves complete ulcer healing (RR 2.11, 95% CI 1.46 to 3.07; 4 studies, 526 participants; moderate-certainty evidence); may slightly increase the reduction in pain from baseline (MD -8.55, 95% CI -14.77 to -2.34; 3 studies, 337 participants); and may slightly increase change in ulcer size, measured as mean reduction from baseline to 45 days (MD 30.44%, 95% CI 15.57 to 45.31; 2 studies, 190 participants). It is uncertain if hyaluronic acid alters incidence of infection when compared with neutral vehicle (RR 0.89, 95% CI 0.53 to 1.49; 3 studies, 425 participants). We are uncertain whether there is a difference in change in ulcer size (cm2) between hyaluronic acid and dextranomer because the certainty of evidence is very low (MD 5.80, 95% CI -10.0 to 21.60; 1 study, 50 participants). We downgraded the certainty of evidence due to risk of bias or imprecision, or both, for all of the above comparisons. No trial reported health-related quality of life or wound recurrence. Measurement of change in ulcer size was not homogeneous among studies, and missing data precluded further analysis for some comparisons. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to determine the effectiveness of hyaluronic acid dressings in the healing of pressure ulcers or foot ulcers in people with diabetes. We found evidence that hyaluronic acid probably improves complete ulcer healing and may slightly decrease pain and increase change in ulcer size when compared with neutral vehicle. Future research into the effects of hyaluronic acid in the healing of chronic wounds should consider higher sample size and blinding to minimise bias and improve the quality of evidence.

Photodynamic therapy for infected foot ulcers in people with diabetes mellitus: a systematic review.

BACKGROUND: Ulceration of the feet in patients with diabetes is a frequent complication that increases morbidity, mortality, hospitalization, treatment costs, and non-traumatic amputations. OBJECTIVE: To present a systematic review of the treatment of patients with diabetes mellitus and infected foot ulcers using photodynamic therapy. DESIGN AND SETTING: A systematic review was performed in the postgraduate program in nursing at the Universidade da Integração Internacional da Lusofonia Afro-Brasileira, Ceará, Brazil. METHODS: PubMed, CINAHL, Web of Science, EMBASE, Cochrane Library, Scopus, and LILACS databases were screened. The methodological quality, risk of bias, and quality of evidence of each study were assessed. Review Manager was used for the meta-analysis. RESULTS: Four studies were included. They highlighted significantly better outcomes in patient groups treated with photodynamic therapy than those in the control groups that were treated with topical collagenase and chloramphenicol (P = 0.036), absorbent (P < 0.001), or dry covers (P = 0.002). Significant improvements were noted in terms of the microbial load in the ulcers and tissue repair, with a reported reduction in the need for amputation by up to 35 times. Photodynamic therapy resulted in significantly better outcomes between the experimental and control groups (P = 0.04). CONCLUSION: Photodynamic therapy is significantly more effective in treating infected foot ulcers than standard therapies. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) - CRD42020214187, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=214187.

Cultivo versus metagenómica para la identificación bacteriana en pacientes con osteomielitis de pie diabético: una revisión sistemática / Culture and metagenomics as bacterial identification methods in patients with diabetic foot ulcers: a systematic review

BACKGROUND: Diabetic foot osteomyelitis (DFO) is a serious complication of infected ulcers in a diabetic patient. The identification of the infecting microorganisms is generally by culture, which causes a bias. Recently, metagenomics has been used for microbial identification. AIM: To systematically review the scientific literature related to DFO in the last 10 years to evaluate if culture and metagenomics are complementary. MATERIAL AND METHODS: To carry out the systematic review, PRISMA and Rayyan were used for the selection of studies, using three databases, using the keywords diabetes, osteomyelitis, culture and microbiome. Articles in English or Spanish were included, containing information related to bacterial identification in DFO. Characteristics of the technique, patients and frequency of bacterial appearance were collected. RESULTS: Twenty six articles were included, 19 used culture and 7 metagenomics. The patients were predominantly men (68%), with an average age of 61 years, 83% had type 2 diabetes and comorbidities, mainly vascular and neuropathy. The Families with the highest frequency of appearance using the culture technique were Enterobacteriaceae (29.3%) and Staphylococcaceae(28.3%) and with metagenomics Peptoniphilaceae (22.1%) and Staphylococcaceae (9.4%). Peptoniphilaceae were not identified in culture, although they were frequently identified by metagenomics. Methicillin- resistant Staphylococcus aureus, regularly identified by culture, was not identified using metagenomics. CONCLUSIONS: Comparing results, there is a certain complementarity between microbiological culture and sequencing to identify bacteria present in DFO.

Treatment of Nonhealing Diabetic Foot Wounds with Vaporous Hyperoxia Therapy in Conjunction with Standard Wound Care.

BACKGROUND: Vaporous hyperoxia therapy (VHT), a patented US Food and Drug Administration 510 (k)-cleared technology, is an adjunct therapy used in conjunction with standard wound care (SWC). Vaporous hyperoxia therapy is said to improve the health of wounded tissue by administering a low-frequency, noncontact, nonthermal, ionic, antimicrobial hydrating mist alternating with concentrated topical oxygen therapy. METHODS: Vaporous hyperoxia therapy was used to treat 36 subjects with chronic diabetic foot ulcers (DFUs) that were previously treated unsuccessfully with SWC. The average age of DFUs in the study was 11 months and the average size was over 3 cm2. Wounds were Wagner grade 2 or 3 and most commonly on the plantar surface around the midfoot. Treatment consisted of twice-weekly applications of VHT and wound debridement. Subjects were followed to wound closure, 20 weeks, or 40 treatments, whichever came first. RESULTS: The combination of SWC and VHT in the group that met and maintained compliance throughout the study period achieved an 83% DFU closure rate within a 20-week period. The average time for DFU closure in this study was 9.4 weeks. CONCLUSIONS: Historical analysis of SWC shows a 30.9% healing rate of all wounds, not differentiating chronic wounds. Accordingly, SWC/VHT increases chronic diabetic foot ulcer healing rates by 2.85 times compared with SWC alone. The purpose of this study was two-fold: first, to observe the effect of VHT on healing rates and time to healing in previously nonhealing DFUs; and second, to compare VHT with SWC, topical oxygen therapy, hyperbaric oxygen therapy, and ultrasound therapy.

Update of Topical Interventions for Healing Diabetic Ulcers-A Systematic Review.

There are a variety of dressings for wound healing. For this reason, research can assist in the choice and proper use of the intervention. This current view of the effectiveness of dressing on diabetic foot ulcers (DFUs) in patients with type 2 diabetes mellitus. This study is a systematic review of clinical trials selected in 4 databases: PubMed, Scopus, Web of Science, and Cochrane. Studies without language restriction, published between 2009 and 2020, were included. The search resulted in the identification of 5651 articles, of which 58 met all inclusion criteria. Among these, 2 biomaterials (D-acellular dermal matrix and keratinocyte) and phenytoin were highlighted for achieving healing rates of 100% and 95.82% ± 2.22%, respectively. The literature presents several alternatives with different actions, cure rates, reduction rates, and varied cost benefits. The growth in the use of biomaterials for the treatment of DFU can be seen in this study.

[Culture and metagenomics as bacterial identification methods in patients with diabetic foot ulcers: a systematic review]. / Cultivo versus metagenómica para la identificación bacteriana en pacientes con osteomielitis de pie diabético: una revisión sistemática.

BACKGROUND: Diabetic foot osteomyelitis (DFO) is a serious complication of infected ulcers in a diabetic patient. The identification of the infecting microorganisms is generally by culture, which causes a bias. Recently, metagenomics has been used for microbial identification. AIM: To systematically review the scientific literature related to DFO in the last 10 years to evaluate if culture and metagenomics are complementary. MATERIAL AND METHODS: To carry out the systematic review, PRISMA and Rayyan were used for the selection of studies, using three databases, using the keywords diabetes, osteomyelitis, culture and microbiome. Articles in English or Spanish were included, containing information related to bacterial identification in DFO. Characteristics of the technique, patients and frequency of bacterial appearance were collected. RESULTS: Twenty six articles were included, 19 used culture and 7 metagenomics. The patients were predominantly men (68%), with an average age of 61 years, 83% had type 2 diabetes and comorbidities, mainly vascular and neuropathy. The Families with the highest frequency of appearance using the culture technique were Enterobacteriaceae (29.3%) and Staphylococcaceae(28.3%) and with metagenomics Peptoniphilaceae (22.1%) and Staphylococcaceae (9.4%). Peptoniphilaceae were not identified in culture, although they were frequently identified by metagenomics. Methicillin- resistant Staphylococcus aureus, regularly identified by culture, was not identified using metagenomics. CONCLUSIONS: Comparing results, there is a certain complementarity between microbiological culture and sequencing to identify bacteria present in DFO.

Evaluation of methanolic crude extract of Linum usitatissimum for the removal of biofilm in diabetic foot isolates / Avaliação do extrato em bruto metanólico de Linum usitatissimum para remoção de biofilmes em isolados diabéticos de pé

Abstract Linum usitatissimum L is a widely used traditionally for multiple ailments. The present research was carried out to explore the antimicrobial, and anti-biofilm activity of crude extract of Linum usitatissimum L (Lu. Cr). Phytochemical and proximate analyses were performed. The bandages of diabetic foot patients were collected from the various hospitals. The bandages were cultured to isolate the bacterial strains present on it. The disc diffusion method was used to identify the antimicrobial potential whereas the minimum inhibitory concentration of the Lu.Cr were also determined. Proximate analysis confirms moisture content 8.33%, ash content 4.33%, crude protein 21.20%, crude fat 49.2% and crude fiber 5.63%. It was revealed that Gram-positive bacteria are most prevalent among all study groups. Lu.Cr possess significant bactericidal potential against S. aureus among all other microbes. Owing to this potential, linseed coated bandages can be used alternatively for the treatment of diabetic foot.

Resumo Linum usitatissimum L é amplamente utilizado tradicionalmente para doenças múltiplas. O presente trabalho foi realizado para explorar a atividade antimicrobiana e antibiofilme do extrato bruto de Linum usitatissimum L (Lu.Cr). Foram realizadas análises fitoquímicas e aproximadas. As ataduras de pacientes diabéticos com pé foram recolhidas nos vários hospitais. As bandagens foram cultivadas para isolar as cepas bacterianas presentes nas mesmas. O método de difusão em disco foi utilizado para identificar o potencial antimicrobiano e a concentração inibitória mínima do Lu.Cr também foi determinada. A análise aproximada confirma o teor de umidade 8,33%, teor de cinzas 4,33%, proteína bruta 21,20%, gordura bruta 49,2% e fibra bruta 5,63%. Foi revelado que as bactérias Gram-positivas são mais prevalentes entre todos os grupos de estudo. Lu.Cr possui potencial bactericida significativo contra S. aureus entre todos os outros micróbios. Devido a esse potencial, as ligaduras revestidas com linhaça podem ser utilizadas alternativamente para o tratamento do pé diabético.

Treatment of chronic wounds with methylene blue photodynamic therapy: A case report.

Methylene blue (MB) mediated photodynamic therapy (PDT) is an emerging treatment for different kinds of skin lesions and ulcers. Our case report aims to assess its potential in treating diabetic foot ulcers, venous leg ulcers, and pressure ulcers. Patients presented with complex chronic wounds larger than 40 cm2 with low healing potential. Once a week, patients had an aqueous formulation of MB at a concentration of 10 mg/mL (1% w/v) applied topically on their wounds, which were then irradiated with a light-emitting diode (LED) light source (660 nm, 3.8 J/cm2) with 9 mW/cm2 on tissue surface. Symptom improvement and recurrence rates were assessed with a long-term follow-up from 2018 to 2021. The results were satisfactory, with significant wound size reduction, and a decrease in aspects indicative of infection including odor, presence of exudates, and purulence. After methylene blue-mediated photodynamic therapy (MB-PDT), patients showed significantly reduced wound secretion, no signs of local reaction, and no adverse effects such as burning sensation, pain, itching, skin erythema, or general malaise.

Microbiota of diabetic foot infections in a University Hospital in Bogotá, Colombia.

The presence of infection in diabetic foot ulcers (DFU) is one of the main causes of lower limb amputation in the world. The presence of polymicrobial infections is usually the standard for isolation in such lesions, with Gram Positive (GP) germs being the main organisms involved, as is described in the global literature. However, some studies indicate a greater number of isolates with Gram Negative (GN) germs, reported mainly in the literature of Middle Eastern countries and in the tropics.

Diabetic Foot Infections: Bacterial Isolates From the Centers and Hospitals of Latin American Countries.

Diabetic foot infections (DFIs) are one of the most important reasons for lower limb amputations. An adequate approach to the management of DFI implies control of infection using strategies of tissue debridement and empirical antibiotic treatment based on local microbiology. The aim of this study was to determine the bacterial isolates profile and antibiotic susceptibility patterns in samples from DFI from Latin American centers, on the premise that microbiology of this region differs from that of other continents and influences antimicrobial election. Three hundred and eighty-two samples from soft tissue and bone were studied from 17 centers of 4 countries. Three hundred and seven (80.4%; 95% confidence interval = 75.9-84.2) were positive. Gram negatives (GN) were isolated in 43.8% of all samples, not only in severe but also in mild infections, 51% in bone samples, more frequently in presence of ischemia (47% vs 38%; P = .07) and in wounds with longer duration of the lesion (30-20 days; P < .01). Staphylococcus aureus was the most frequent single germ (19.9%). Gram positives were isolated more frequently in patients without ischemia (53% vs 40%; P = .01). Enterococcus faecalis was the most frequent germ in bone samples (16.8%). Ciprofloxacin and trimethoprim-sulfamethoxazole were the oral antimicrobials most effective against GN. Trimethoprim-sulfamethoxazole and rifampicin were the oral antimicrobials most effective against Staphylococcus. Because of GN high antibiotic resistance patterns, patients treated in an ambulatory setting have to be controlled early after starting empiric treatment to assess response to therapy and hospitalize for parenteral antibiotics if oral treatment fails.

Wound Chronicity, Impaired Immunity and Infection in Diabetic Patients.

BACKGROUND: Diabetic foot ulcers are a common diabetic complication leading to alarming figures of amputation, disability, and early mortality. The diabetic glucooxidative environment impairs the healing response, promoting the onset of a 'wound chronicity phenotype'. In 50% of ulcers, these non-healing wounds act as an open door for developing infections, a process facilitated by diabetic patients' dysimmunity. Infection can elicit biofilm formation that worsens wound prognosis. How this microorganism community is able to take advantage of underlying diabetic conditions and thrive both within the wound and the diabetic host is an expanding research field. OBJECTIVES: 1) Offer an overview of the major cellular and molecular derangements of the diabetic healing process versus physiological cascades in a non-diabetic host. 2) Describe the main immunopathological aspects of diabetics' immune response and explore how these contribute to wound infection susceptibility. 3) Conceptualize infection and biofilim in diabetic foot ulcers and analyze their dynamic interactions with wound bed cells and matrices, and their systemic effects at the organism level. 4) Offer an integrative conceptual framework of wound-dysimmunity-infection-organism damage. EVIDENCE AQUISITION: We retrieved 683 articles indexed in Medline/PubMed, SciELO, Bioline International and Google Scholar. 280 articles were selected for discussion under four major subheadings: 1) normal healing processes, 2) impaired healing processes in the diabetic population, 3) diabetic dysimmunity and 4) diabetic foot infection and its interaction with the host. DEVELOPMENT: The diabetic healing response is heterogeneous, torpid and asynchronous, leading to wound chronicity. The accumulation of senescent cells and a protracted inflammatory profile with a pro-catabolic balance hinder the proliferative response and delay re-epithelialization. Diabetes reduces the immune system's abilities to orchestrate an appropriate antimicrobial response and offers ideal conditions for microbiota establishment and biofilm formation. Biofilm-microbial entrenchment hinders antimicrobial therapy effectiveness, amplifies the host's pre-existing immunodepression, arrests the wound's proliferative phase, increases localized catabolism, prolongs pathogenic inflammation and perpetuates wound chronicity. In such circumstances the infected wound may act as a proinflammatory and pro-oxidant organ superimposed onto the host, which eventually intensifies peripheral insulin resistance and disrupts homeostasis. CONCLUSIONS: The number of lower-limb amputations remains high worldwide despite continued research efforts on diabetic foot ulcers. Identifying and manipulating the molecular drivers underlying diabetic wound healing failure, and dysimmunity-driven susceptibility to infection will offer more effective therapeutic tools for the diabetic population.

Registro sanitario de Heberprot-P®, medicamento biotecnológico innovador para el tratamiento de las úlceras del pie diabético / Sanitary registration of Heberprot-P®, an innovative biotechnological drug for the treatment of diabetic foot ulcers

Introducción: Heberprot-P® obtuvo su primer registro sanitario en Cuba en el año 2006, actualmente está aprobado en otros 26 países. Objetivo: Describir el proceso de registro sanitario en México, del medicamento biotecnológico Heberprot-P® para el tratamiento de las úlceras del pie diabético. Métodos: El proceso de registro sanitario de Heberprot-P® siguió las pautas de la reglamentación sanitaria de México sobre la base de la Ley general de salud y el Reglamento de insumos para la salud. Se revisaron además la Farmacopea de los Estados Unidos Mexicanos y las normas oficiales mexicanas en función de cumplir las exigencias para la comercialización de medicamentos en este territorio. Resultados: El proceso de registro se inició en junio de 2017 en México con acciones en función de completar los documentos e informaciones exigidas en el expediente de registro sanitario a presentarse. Entre ellos resaltan las consideraciones del Subcomité de Evaluación de Productos Biotecnológicos y el Comité de Moléculas Nuevas, la evaluación del expediente por un Tercero Autorizado y documentos emitidos por el Centro Nacional de Farmacovigilancia e Instituto Mexicano de la Propiedad Industrial. Se presentó la solicitud del registro sanitario ante Cofepris y esta se aprobó en mayo de 2018. Conclusiones: El trabajo con grupos de expertos permitió a la autoridad mexicana hacer un trabajo más expedito basado en las evidencias de las evaluaciones realizadas que son parte de la información del registro sanitario. Como resultado de este proceso, se otorgó el Registro Sanitario a Heberprot-P® en mayo de 2018 y Cofepris lo reconoció como un medicamento biotecnológico innovador(AU)

Introduction: Heberprot-P® obtained its first Sanitary Registration in Cuba in 2006, and it is currently approved in 26 other countries. Objective: Describe the sanitary registration process in Mexico of the biotechnological drug Heberprot-P® for the treatment of diabetic foot ulcers. Methods: The sanitary registration process of Heberprot-P® followed the guidelines of the sanitary regulations of Mexico on the basis of the General Health Law and the Regulation of Supplies for Health. The Pharmacopoeia of the United Mexican States and the official Mexican standards were also revised in order to comply with the requirements for the marketing of medicines in this territory. Results: The registration process began in June 2017 in Mexico with actions to complete the documents and information required in the sanitary registration file to be submitted. Among them are the considerations of the Sub-committee on the Evaluation of Biotechnological Products and the Committee on New Molecules, the evaluation of the file by an Authorized Third Party and documents issued by the National Center for Pharmacovigilance and the Mexican Institute of Industrial Property. The application for sanitary registration was submitted to Cofepris and this was approved in May 2018. Conclusions: The work with groups of experts allowed the Mexican authority to do a more expeditious work based on the evidence of the evaluations carried out that are part of the information of the sanitary registry. As a result of this process, Heberprot-P® was granted the Sanitary Registry in May 2018 and COFEPRIS recognized it as an innovative biotechnological medicine(AU)

Evaluation of methanolic crude extract of Linum usitatissimum for the removal of biofilm in diabetic foot isolates.

Linum usitatissimum L is a widely used traditionally for multiple ailments. The present research was carried out to explore the antimicrobial, and anti-biofilm activity of crude extract of Linum usitatissimum L (Lu. Cr). Phytochemical and proximate analyses were performed. The bandages of diabetic foot patients were collected from the various hospitals. The bandages were cultured to isolate the bacterial strains present on it. The disc diffusion method was used to identify the antimicrobial potential whereas the minimum inhibitory concentration of the Lu.Cr were also determined. Proximate analysis confirms moisture content 8.33%, ash content 4.33%, crude protein 21.20%, crude fat 49.2% and crude fiber 5.63%. It was revealed that Gram-positive bacteria are most prevalent among all study groups. Lu.Cr possess significant bactericidal potential against S. aureus among all other microbes. Owing to this potential, linseed coated bandages can be used alternatively for the treatment of diabetic foot.

Health Care Spending in Patients With Stage 3 and Stage 4 Pressure Injuries and Patients With Diabetic Foot Ulcers Treated Early With Clostridial Collagenase Ointment: A Retrospective Data Review.

INTRODUCTION: Clostridial collagenase ointment (CCO) is the only enzymatic agent indicated for debriding chronic dermal ulcers that is approved by the United States Food and Drug Administration. OBJECTIVE: The objective of this study is to estimate health care spending among patients with Stage 3 and Stage 4 pressure injuries (PIs) and patients with diabetic foot ulcers (DFUs) who experienced early (ie, within 30 days of index diagnosis) versus late (31 to 90 days of index diagnosis) initiation of CCO. METHODS: Patients with PIs and DFUs between January 2007 and March 2017 were identified. One-to-one matched cohorts were used to compare all-cause health care spending and disease-related health care spending between the early initiation and late initiation groups. RESULTS: Compared to the early CCO initiation group, all-cause health care spending for the late CCO initiation group was higher in both patients with PIs and in patients with DFUs within the 12-month follow-up period. Compared to the early CCO initiation group, disease-related health care spending for the late CCO initiation group was higher in both patients with PIs and in patients with DFUs within the 12-month follow-up period. All computations were statistically significant. CONCLUSIONS: Early initiation of CCO provides both all-cause and disease-related health care savings to payers and persons managing patients with PIs or DFUs. Payers, providers, and facilities should consider mechanisms to encourage the early use of CCO to lower costs.

Eficacia y seguridad de polihexanida 0. 1 % más undecilenamidopropil betaina 0. 1 % en pacientes con heridas crónicas en piel / Efficacy and safety of polyhexanide 0. 1% plus undecylenamidopropyl betaine 0. 1% in patients with chronic skin wounds

INTRODUCCIÓN: El presente dictamen preliminar expone la evaluación de tecnología sanitaria (ETS) del antiséptico1 polihexanida 0.1 %, o polihexametilen biguanida, con betaína 0.1 % (PHMB), en solución o gel, en comparación con solución salina normal (SSN), para la limpieza de heridas crónicas en piel (úlceras de presión, úlceras venosas, úlceras isquémicas arteriales o úlceras diabéticas). Las heridas crónicas en piel, son aquellas que no logran culminar el proceso de cicatrización luego de 8 a 12 semanas. Las heridas crónicas pueden llegar a representar una alta carga para el paciente, al sistema de salud y para la sociedad, no sólo por el costo del tratamiento, sino porque pueden llegar a generar discapacidad, además del impacto emocional y social al limitar la funcionalidad del individuo. En la actualidad, el manejo inicial de las heridas crónicas se basa en emplear SSN para realizar la limpieza de las heridas crónicas mediante el uso de gasas remojadas con SSN con la intención de realizar la limpieza del lecho de la herida, evitar el acúmulo de tejido muerto, del crecimiento bacteriano y permitir la granulación adecuada, y, por ende, la curación adecuada de la herida. Sin embargo, se considera que al formarse un biofilm, el lecho de la herida se vuelve resistente al efecto de arrastre del SSN, debido a la capa lipídica que lo cubre, pudiendo favorecer el crecimiento bacteriano e incrementando el riesgo de infección de las heridas crónicas. METODOLOGÍA; Se llevó a cabo una revisión de la literatura publicada a la fecha (octubre;, 2020) y la síntesis de resultados con respecto a la eficacia y seguridad de PHMB, solución o gel, en comparación con SSN, en pacientes con heridas crónicas en piel. Se identificaron cuatro guías de práctica clínica (GPC), de las cuales tres fueron elaboradas por la Sociedad de la Curación de Heridas (WHS, por sus siglas en inglés) (Lavery et al., 2018; Marston et al., 2015; Gould et al., 2015), y una GPC de la Agencia Ejecutiva para la Salud y Seguridad del Reino Unido (HSE, por sus siglas en inglés) (Nolan et al., 2018), una ETS del Ministerio de Salud de Argentina (Hasdeu et al., 2018), una revisión sistemática (RS) de To et al., 2016 y dos ensayos clínicos aleatorizados (ECA) (Bellingeri et al., 2018 y Romanelli et al., 2010) que respondieron a la pregunta PICO (acrónimo de P=población, I=intervención, C=comparador y O=outcome o desenlace). RESULTADOS: Como producto de la búsqueda bibliográfica, se han incluido cuatro GPC, una ETS, una RS y dos ECA que responden a la pregunta PICO (Tabla N° 1). A continuación, se describe la evidencia disponible según el orden jerárquico del nivel de evidencia o pirámide de Haynes 6S8, siguiendo lo indicado en los criterios de elegibilidad. CONCLUSIONES: El presente dictamen expone la evaluación de la mejor evidencia disponible a la fecha (octubre, 2020) respecto a la eficacia y seguridad del uso del agente antiséptico Polihexanida 0.1 % más undecilenamidopropil betaina 0.1 % para la limpieza de heridas crónicas en piel (úlceras por presión, úlceras por estasis venosa, úlceras diabéticas y úlceras isquémicas arteriales), en comparación con SSN. Como producto de una búsqueda bibliográfica y un proceso de selección de la evidencia, se han incluido en el presente dictamen preliminar cuatro guías de práctica clínica (GPC), de las cuales tres fueron elaboradas por WHS (Lavery et al., 2018; Marston et al., 2015; Gould et al., 2015), y una por la HSE (Nolan et al., 2018), una ETS del Ministerio de Salud de Argentina (Hasdeu et al., 2018), una revisión sistemática (RS) de To et al., 2016 y dos ensayos clínicos aleatorizados (ECA) (Bellingeri et al., 2018 y Romanelli et al., 2010) que respondieron a la pregunta PICO. Las cuatro guías incluidas en el presente dictamen no contienen recomendaciones específicas sobre el uso de PHMB, solución o gel, ni sobre SSN para la limpieza de las heridas crónicas. A pesar de ello, las guías si mencionan que la SSN es recomendado frecuentemente en la práctica diaria, por lo que sería una intervención aceptable. Además, en el caso de la guía para úlceras por presión, se recomienda evitar el uso de antiséptico para la limpieza de las heridas crónicas. Además, la guía de la HSE refiere que el manejo del biofilm debe ser multimodal, sin mencionar una solución en particular. Con respecto a la ETS, si bien recomienda de manera débil el uso de PHMB, los autores de la ETS no brindan evidencia que permita justificar el empleo de PHMB solución, en vez de SSN, en la curación de úlceras en pie diabético. La RS de To et al., 2016 muestra que el único estudio identificado que responde a la pregunta PICO del presente dictamen es el estudio de Romanelli et al., 2010, el cual refiere una disminución en el nivel de dolor, sin presentar valores específicos mas no en la curación de la herida. Así, no reporta evidencia sólida sobre algún beneficio clínicamente relevante sobre el uso de PHMB solución en vez de SSN para el manejo de las heridas crónicas. El ECA de Bellingeri et al., 2016 reporta que el uso de PHMB solución reduce el puntaje BWAT, representando una mejora en el proceso de cicatrización, también reporta que no hay diferencias en el nivel de dolor y la ocurrencia de eventos adversos. Sin embargo, dado las diferentes limitaciones metodológicas identificadas, como no lograr completar el número de participantes preestablecido, no reportar los resultados de manera precisa, además de ser de etiqueta abierta, y de corta duración (28 días), este estudio no permite sustentar el uso de PHMB solución en vez de SSN, para la limpieza de las heridas crónicas. Por otro lado, el ECA de Romanelli et al., 2010 no mostró diferencias en la reducción del tamaño de las heridas, ni en la presentación de eventos adversos entre los que recibieron PHMB solución y SSN por cuatro semanas, más si en el nivel de dolor reportado, a pesar de ello, el estudio no reporta los valores precisos en los desenlaces de interés. Además, este estudio presenta severas limitaciones metodológicas al ser de etiqueta abierta, tener un tiempo de seguimiento corto, no haber realizado el cálculo de tamaño de muestra, además de haber recibido financiamiento de la industria. Por lo que, no es posible concluir con respecto a una superioridad de PHMB sobre SSN para la limpieza de heridas crónicas. De este modo, la evidencia recopilada sobre PHMB, solución o gel, como tratamiento de las heridas crónicas, en comparación con SSN es deficiente y cuenta con severas limitaciones metodológicas. Así, se concluye que la evidencia disponible no permite identificar algún beneficio clínicamente relevante con PHMB, solución o gel, en comparación con SSN, para la limpieza de las heridas crónicas. Además, cabe resaltar que la mayoría de las guías evaluadas refieren el uso de SSN para la limpieza de heridas crónicas, tecnología sanitaria que se encuentra en el catálogo de bienes de EsSalud. Por lo expuesto, el IETSI no aprueba el uso de PHMB, solución o gel, para el tratamiento de pacientes con heridas crónicas en piel.

Epidermal Growth Factor in Healing Diabetic Foot Ulcers: From Gene Expression to Tissue Healing and Systemic Biomarker Circulation.

Lower-extremity diabetic ulcers are responsible for 80% of annual worldwide nontraumatic amputations. Epidermal growth factor (EGF) reduction is one of the molecular pillars of diabetic ulcer chronicity, thus EGF administration may be considered a type of replacement therapy. Topical EGF ad-ministration to improve and speed wound healing began in 1989 on burn patients as part of an acute-healing therapy. Further clinical studies based on topically administering EGF to different chronic wounds resulted in disappointing out-comes. An analysis of the literature on unsuccessful clinical trials identifi ed a lack of knowledge concerning: (I) molecular and cellular foundations of wound chronicity and (II) the phar-macodynamic requisites governing EGF interaction with its receptor to promote cell response. Yet, EGF intra- and perile-sional infi ltration were shown to circumvent the pharmacody-namic limitations of topical application. Since the fi rst studies, the following decades of basic and clinical research on EGF therapy for problem wounds have shed light on potential uses of growth factors in regenerative medicine. EGF's molecular and biochemical effects at both local and systemic levels are diverse: (1) downregulation of genes encoding infl ammation mediators and increased expression of genes involved in cell proliferation, angiogenesis and matrix secretion; (2) EGF in-tervention positively impacts both mesenchymal and epithelial cells, reducing infl ammation and stimulating the recruitment of precursor circulating cells that promote the formation of new blood vessels; (3) at the subcellular level, upregulation of the EGF receptor with subsequent intracellular traffi cking, includ-ing mitochondrial allocation along with restored morphology of multiple organelles; and (4) local EGF infi ltration resulting in a systemic, organismal repercussion, thus contributing to attenuation of circulating infl ammatory and catabolic reac-tants, restored reduction-oxidation balance, and decreased toxic glycation products and soluble apoptogenic effectors. It is likely that EGF treatment may rearrange critical epigenetic drivers of diabetic metabolic memory. KEYWORDS Epidermal Growth Factor, diabetes, diabetes complications, wound healing, diabetic foot, amputation, ulcer, Cuba.