Prolonged Beta-Lactam Infusions in Children: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess whether beta-lactam extended or continuous beta-lactam infusions (EI/CI) improve clinical outcomes in children with proven or suspected bacterial infections. STUDY DESIGN: We included observational and interventional studies that compared beta-lactam EI or CI with standard infusions in children less than 18 years old, and reported on mortality, hospital or intensive care unit length of stay, microbiological cure, and/or clinical cure. Data sources included PubMed, Medline, EBM Reviews, EMBASE, and CINAHL and were searched from January 1, 1980, to November 3, 2023. Thirteen studies (2945 patients) were included: 5 randomized control trials and 8 observational studies. Indications for antimicrobial therapies and clinical severity varied, ranging from cystic fibrosis exacerbation to critically ill children with bacteriemia. RESULTS: EI and CI were not associated with a reduction in mortality in randomized control trials (n = 1464; RR 0.93, 95% CI 0.71, 1.21), but were in observational studies (n = 833; RR 0.43, 95% CI 0.19, 0.96). We found no difference in hospital length of stay. Results for clinical and microbiological cures were heterogeneous and reported as narrative review. The included studies were highly heterogeneous, limiting the strength of our findings. The lack of shared definitions for clinical and microbiological cure outcomes precluded analysis. CONCLUSIONS: EI and CI were not consistently associated with reduced mortality or length of stay in children. Results were conflicting regarding clinical and microbiological cures. More well-designed studies targeting high-risk populations are necessary to determine the efficacy of these alternative dosing strategies.

In silico optimization of analogs derived pro-adrenomedullin peptide to evaluate antimicrobial potential.

Diverse computational approaches have been widely used to assist in designing antimicrobial peptides with enhanced activities. This tactic has also been used to address the need for new treatment alternatives to combat resistant bacterial infections. Herein, we have designed eight variants from a natural peptide, pro-adrenomedullin N-terminal 20 peptide (PAMP), using an in silico pattern insertion approach, the Joker algorithm. All the variants show an α-helical conformation, but with differences in the helix percentages according to circular dichroism (CD) results. We found that the C-terminal portion of PAMP may be relevant for its antimicrobial activities, as revealed by the molecular dynamics, CD, and antibacterial results. The analogs showed variable antibacterial potential, but most were not cytotoxic. Nevertheless, PAMP2 exhibited the most potent activities against human and animal-isolated bacteria, showing cytotoxicity only at a substantially higher concentration than its minimal inhibitory concentration (MIC). Our results suggest that the enhanced activity in the profile of PAMP2 may be related to their particular physicochemical properties, along with the adoption of an amphipathic α-helical arrangement with the conserved C-terminus portion. Finally, the peptides designed in this study can constitute scaffolds for the design of improved sequences.

Factors Associated With Extrapulmonary Tuberculosis in Southeastern Mexico: A Case-Control Study.

INTRODUCTION: Extrapulmonary tuberculosis (EPTB) is a disease that can affect any organ or tissue. Due to its potential to cause more dangerous sequelae and the barriers to its timely diagnosis, greater clinical awareness of this disease is crucial. This study aimed to identify the factors associated with EPTB in the population of Oaxaca, Mexico. METHODS: This is an unpaired case-control study. The cases were patients with EPTB+ while the controls were patients with pulmonary tuberculosis (PTB+) registered in the Tuberculosis Epidemiological Surveillance System. Sociodemographic, clinical, and microbiological variables were recovered. Bivariate analyses were performed and logistic regression analyses were performed to calculate the odds ratio (OR). RESULTS: A total of 75 EPTB+ cases and 300 PTB+ controls were included. Of the total sample, 57.1% were men and 60.3% indigenous. The most frequent clinical presentations of EPTB+ were nodal (21.3%), miliary (21.3%), and breast (20.0%). According to logistic regression analysis, age <40 years (OR: 2.25 (95% CI: 1.13-4.49), female sex (OR: 1.92 (95% CI: 1.03-3.56)], urban residence (OR: 2.25 (95% CI: 1.11-4.55)), comorbidity with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) (OR: 3.46 (95% CI: 1.31-9.10)), dyspnea (OR: 2.67 (1.22-5.82)), and adenopathy (OR: 3.38 (95% CI: 1.42-8.06)) were positively associated with EPTB+. CONCLUSION: These results can serve as a basis for screening EPTB+, thus improving the preventive and diagnostic capacity of local health services, taking as a starting point women under 40 years of age and patients with HIV/AIDS in urban areas, as well as the presence of adenopathy and dyspnea as clinical characteristics of the disease.

Fatal co-infection by multiple pathogens in an indigenous woman with autoimmune hemolytic anemia and tuberculosis: a case report.

BACKGROUND: Tuberculosis (TB), one of the leading causes of death worldwide, has a higher incidence among indigenous people. Albeit uncommon, autoimmune hemolytic anemia (AIHA) has been deemed a risk condition to develop mycobacterial infection, as a result of the immunosuppressive treatments. TB, in turn, can be a predisposing factor for secondary infections. CASE PRESENTATION: Here we present a case of a 28-year-old indigenous woman from Colombia, previously diagnosed with AIHA and pulmonary TB. Despite various treatments, therapies and medical interventions, the patient died after severe medullary aplasia of multiple causes, including secondary myelotoxicity by immunosuppressive therapy and secondary disseminated infections, underlining infection by Staphylococcus aureus, Klebsiella pneumoniae and Candida glabrata, which were identified as drug-resistant microorganisms. Together, this led to significant clinical complications. Invasive aspergillosis was diagnosed at autopsy. CONCLUSIONS: This report presents a rarely finding of AIHA followed by TB, and highlights the great challenges of dealing with co-infections, particularly by drug resistant pathogens. It also aims to spur governments and public health authorities to focus attention in the prevention, screening and management of TB, especially among vulnerable communities, such as indigenous people.

WHAT IS THE EPIDEMIOLOGICAL PROFILE OF ACUTE HAND INFECTIONS AT A HOSPITAL IN SAO PAULO?

Objective: To determine the epidemiological profile of patients treated at a philanthropic hospital specialized in Orthopedics and Traumatology, located in a significant urban center, and evaluate the efficacy of initial empirical antibiotic treatment. Methods: Patients diagnosed with hand infections from September 2020 to September 2022 were included, excluding cases related to open fractures or post-surgical infections and those with incomplete medical records. The chi-square test was performed using STATISTICA ® software to correlate various variables. Results: A total of 34 patients participated, including 24 men and 10 women, with an average age of 41.9 years. Most male patients had Diabetes Mellitus, HIV, and drug addiction, and they resided in urban areas. Half of the patients did not report any apparent trauma. The most common infectious agent was Staphylococcus aureus*. Nearly 62% of patients required a change in the initial antibiotic regimen, with Penicillin being the most frequently substituted medication. Beta-lactam antibiotics and Quinolones were the most effective. Conclusion: These results suggest the importance of carefully evaluating the epidemiological profile of patients with acute hand infections and improving initial empirical treatment to ensure appropriate and effective therapy. Level of Evidence IV, Cross-Sectional Observational Study.

Objetivo: Determinar o perfil epidemiológico de pacientes atendidos em um hospital filantrópico referência em Ortopedia e Traumatologia localizado em um centro urbano importante, e avaliar a eficácia do tratamento antibiótico empírico inicial. Métodos: Foram incluídos pacientes com diagnóstico de infecção na mão, atendidos no período de setembro de 2020 a setembro de 2022, excluindo-se casos relacionados a fraturas expostas ou pós-cirúrgicas e aqueles com prontuários incompletos. Realizou-se o teste do qui-quadrado, utilizando o software STATISTICA ® para correlacionar diversas variáveis. Resultados: Participaram do estudo 34 pacientes, sendo 24 homens e 10 mulheres, com média de idade de 41,9 anos. A maioria era de homens, com alta incidência de diabetes mellitus, HIV e drogadição, que residiam em áreas livres. Metade não relatou trauma evidente. O agente infeccioso mais comum foi o Staphylococcus aureus. Aproximadamente 62% dos pacientes precisaram de troca do esquema inicial de antibióticos, sendo a penicilina o medicamento mais frequentemente substituído. Os antibióticos beta-lactâmicos e quinolonas foram os mais eficientes. Conclusão: Esses resultados sugerem a importância de avaliar cuidadosamente o perfil epidemiológico dos pacientes com infecções agudas na mão e aprimorar o tratamento empírico inicial para garantir uma terapia adequada e eficaz. Nível de Evidência IV, Estudo Observacional Transversal.

Adesão aos bundles de prevenção a infecções relacionadas à assistência à saúde / Adherence to bundles for prevention of infections related to health cares / Adhesión a los paquetes para la prevención de infecciones relacionadas com la atención médica

Objetivo: Analisar a adesão aos bundles de prevenção a infecções relacionadas a assistência à saúde. Métodos: Trata-se de um estudo transversal, realizado com dados secundários a partir de registros em fichas de notificação e investigação, além de prontuários de pacientes. Foram analisados Bundles de prevenção para Pneumonia por Assistência Ventilatória, Cateter Venoso Central, Cateter Vesical de Demora e Higiene de Mãos. Estatísticas descritivas e de tendência central foram aplicadas a todas as variáveis. Resultados: A adesão ao Bundle de Pneumonia por Assistência Ventilatória mostrou índices médios de 56,6%. Em relação ao de Cateter Vesical de Demora sua adesão alcançou 100% na maioria dos meses estudados. Para o Bundle de Cateter Venoso Central houve prevalência de 97,1% de adesão. Já a adesão a higienização das mãos, apontou resultados superiores a 94,2%, chegando a 97,1%. Conclusão: A assistência aos pacientes deve ocorrer de forma sistemática e multidisciplinar pelos profissionais de saúde para que medidas corretas e eficazes sejam adotadas. (AU)

Objective: To analyze adherence to healthcare-related infection prevention bundles. Methods: This is a cross-sectional study, performed with secondary data from records in notification and investigation forms, in addition to patient records. Bundles for prevention of Pneumonia by Ventilatory Assistance, Central Venous Catheter, Delayed Vesical Catheter and Hand Hygiene were analyzed. Descriptive and central tendency statistics were applied to all variables. Results: Adherence to the Pneumonia Bundle for Ventilatory Assistance showed average rates of 56.64%. In relation to the Demora Vesical Catheter, its adherence reached 100% in most months studied. For the Central Venous Catheter Bundle there was a prevalence of 97.06% adherence. Adherence to hand hygiene showed results above 94.23%, reaching 97.14%. Conclusion: Patient care must occur in a systematic and multidisciplinary way by health professionals so that correct and effective measures are adopted. (AU)

Objetivo: analizar la adherencia a los paquetes de prevención de infecciones relacionadas con la salud. Métodos: Se trata de un estudio transversal, realizado con datos secundarios de registros en formularios de notificación e investigación, además de histórias clínicas. Se analizaron los paquetes para la prevención de la neumonía por asistencia ventilatoria, catéter venoso central, catéter vesical retardado e higiene de manos. A todas las variables se les aplicó estadística descriptiva y de tendencia central. Resultados: La adherencia al paquete de neumonía para asistencia respiratoria mostró tasas promedio de 56,64%. En relación al Catéter Demora Vesical, su adherencia alcanzó el 100% en la mayoría de los meses estudiados. Para el paquete de catéter venoso central hubo una prevalencia de adherencia del 97,06%. La adherencia a la higiene de manos mostró resultados superiores al 94,23%, alcanzando el 97,14%. Conclusión: La atención al paciente debe darse de forma sistemática y multidisciplinar por parte de los profesionales sanitarios para que se adopten las medidas correctas y eficaces. (AU)

MASTer cell: chief immune modulator and inductor of antimicrobial immune response.

Mast cells have long been recognized for their involvement in allergic pathology through the immunoglobulin E (IgE)-mediated degranulation mechanism. However, there is growing evidence of other "non-canonical" degranulation mechanisms activated by certain pathogen recognition receptors. Mast cells release several mediators, including histamine, cytokines, chemokines, prostaglandins, and leukotrienes, to initiate and enhance inflammation. The chemical nature of activating stimuli influences receptors, triggering mechanisms for the secretion of formed and new synthesized mediators. Mast cells have more than 30 known surface receptors that activate different pathways for direct and indirect activation by microbes. Different bacterial strains stimulate mast cells through various ligands, initiating the innate immune response, which aids in clearing the bacterial burden. Mast cell interactions with adaptative immune cells also play a crucial role in infections. Recent publications revealed another "non-canonical" degranulation mechanism present in tryptase and chymase mast cells in humans and connective tissue mast cells in mice, occurring through the activation of the Mas-related G protein-coupled receptor (MRGPRX2/b2). This receptor represents a new therapeutic target alongside antibiotic therapy. There is an urgent need to reconsider and redefine the biological role of these MASTer cells of innate immunity, extending beyond their involvement in allergic pathology.

Phage Delivery Strategies for Biocontrolling Human, Animal, and Plant Bacterial Infections: State of the Art.

This review aims at presenting the main strategies that are currently available for the delivery of bacteriophages to combat bacterial infections in humans, animals, and plants. It can be seen that the main routes for phage delivery are topical, oral, systemic, and airways for humans. In animals, the topical and oral routes are the most used. To combat infections in plant species, spraying the plant's phyllosphere or drenching the soil are the most commonly used methods. In both phage therapy and biocontrol using phages, very promising results have been obtained so far. However, more experiments are needed to establish forms of treatment and phage doses, among other parameters. Furthermore, in general, there is a lack of specific standards for the use of phages to combat bacterial infections.

Prevalence of bacterial infections and antimicrobial resistance profile in hospitalized patients with COVID-19 / Prevalência de infecções bacterianas e perfil de resistência aos antimicrobianos em pacientes internados com COVID-19 / Prevalencia de infecciones bacterianas y perfil de resistencia antimicrobiana en pacientes hospitalizados con COVID-19

Background and Objectives: bacterial resistance is an important public health problem worldwide and is related to the indiscriminate use of antimicrobials, limiting the available therapeutic options. The COVID-19 pandemic aggravated this scenario, since the lack of a standardized therapy led to a considerable increase in the prescription of these drugs. Therefore, we proposed to investigate the prevalence of bacterial infections and the profile of antimicrobial resistance in patients diagnosed with COVID-19 as well as to point out possible risk factors. Methods: a retrospective study based on the analysis of medical records of patients hospitalized with COVID-19 over the age of 18. Information such as age, gender, length of stay, hospitalization unit, bacterial species and resistance profile and previous use of antimicrobials by patients diagnosed with COVID-19 were collected and analyzed using Excel® 2016. Results: of the 268 patients with COVID-19, 162 had suspected bacterial infections, and 26 patients (9.7%) were confirmed from positive cultures. Furthermore, around 80% of these patients underwent empirical treatment with antimicrobials, the majority of whom were male and admitted to the Intensive Care Unit. A total of 32 bacterial isolates were recovered, of which 59.4% were resistant to at least one class of antimicrobials, with 21.8% being multidrug resistant. Conclusion: despite the low percentage found of patients with COVID-19 who had bacterial infections and of these 21.8% were by multidrug-resistant bacteria, the reinforcement in infection prevention policies and the adequate management in the release of antimicrobials is necessary to reduce the hospital dissemination rates of such bacteria.(AU)

Justificativa e Objetivos: a resistência bacteriana é um importante problema de saúde pública mundial relacionado ao uso indiscriminado de antimicrobianos, limitando as opções terapêuticas disponíveis. A pandemia de COVID-19 agravou esse cenário, uma vez que a falta de uma terapia padronizada resultou no aumento considerável na prescrição desses fármacos. Diante disso, propôs-se investigar a prevalência de infecções bacterianas e o perfil de resistência aos antimicrobianos em pacientes diagnosticados com COVID-19, bem como apontar possíveis fatores de risco. Métodos: estudo retrospectivo baseado na análise de prontuários de pacientes internados com COVID-19 com idade superior a 18 anos. Informações como idade, gênero, tempo de internação, unidade de internação, espécie bacteriana e perfil de resistência e uso prévio de antimicrobianos pelos pacientes diagnosticados com COVID-19 foram coletadas e analisadas pelo software Excel® 2016. Resultados: dos 268 pacientes com COVID-19, 162 apresentaram suspeitas de infecções bacterianas, sendo 26 pacientes (9,7%) confirmados a partir de culturas positivas. Ainda, cerca de 80% desses pacientes realizaram tratamento empírico com antimicrobianos, sendo a maioria do sexo masculino e internados em Unidade de Terapia Intensiva. Foram recuperados um total de 32 isolados bacterianos, dos quais 59,4% apresentaram resistência a pelo menos uma classe de antimicrobianos, sendo 21,8% multidroga resistente. Conclusão: apesar do baixo percentual encontrado de pacientes com COVID-19 que apresentaram infecções bacterianas e, desses, 21,8% serem causados por bactérias multirresistentes, o reforço nas políticas de prevenção de infecções e o adequado gerenciamento na liberação de antimicrobianos se fazem necessários para a redução das taxas de disseminação hospitalar de tais bactérias.(AU)

Justificación y Objetivos: la resistencia bacteriana es un importante problema de salud pública en todo el mundo y está relacionada con el uso indiscriminado de antimicrobianos, lo que limita las opciones terapéuticas disponibles. La pandemia por COVID-19 agravó este escenario, ya que la falta de una terapia estandarizada llevó a un aumento considerable en la prescripción de estos fármacos. Por ello, nos propusimos investigar la prevalencia de infecciones bacterianas y el perfil de resistencia antimicrobiana en pacientes diagnosticados de COVID-19, así como señalar posibles factores de riesgo. Métodos: estudio retrospectivo basado en el análisis de historias clínicas de pacientes hospitalizados con COVID-19 mayores de 18 años. Información como edad, sexo, duración de la estadía, unidad de hospitalización, especies bacterianas y perfil de resistencia y uso previo de antimicrobianos por parte de pacientes diagnosticados con COVID-19 fueron recopiladas y analizadas mediante el software Excel® 2016. Resultados: de los 268 pacientes con COVID-19, 162 tenían sospecha de infección bacteriana, con 26 pacientes (9,7%) confirmada a partir de cultivos positivos. Además, alrededor del 80% de estos pacientes recibieron tratamiento empírico con antimicrobianos, la mayoría de los cuales eran hombres e ingresaron en la Unidad de Cuidados Intensivos. Se recuperaron un total de 32 aislados bacterianos, de los cuales el 59,4% eran resistentes a al menos una clase de antimicrobianos y el 21,8% eran resistentes a múltiples fármacos. Conclusión: a pesar del bajo porcentaje encontrado de pacientes con COVID-19 que presentaron infecciones bacterianas, y de éstas cerca del 21,8% fueron por bacterias multirresistentes, es necesario reforzar las políticas de prevención de infecciones y una gestión adecuada en la liberación de antimicrobianos para reducir las tasas de diseminación hospitalaria de dichas bacterias.(AU)

Botanical Extracts and Compounds of Castanea Plants and Methods of Use: US20190125818A1 - The United States Patent Evaluation.

BACKGROUND: Bacterial infections are increasingly difficult to combat, which makes them a threat to public health on a global level. Staphylococcus aureus is considered one of the main causes of infections in hospitals, as it has a variety of virulence factors, as well as is able to produce bacterial biofilms, which, consequently, bring numerous damages to public health as a result of increased resistance to conventional antibiotics and a longer hospital stay. Therefore, the use of compounds extracted from medicinal plants is a potential pharmaceutically acceptable target, as they do not have toxicity and the potential to disrupt biofilms produced by Staphylococcus aureus already evidenced, thus revealing their relevance to our study. OBJECTIVE: The objective of this work was to perform a critical analysis of a patent with natural extracts against bacterial biofilms found in the United States Patent and Trademark Office (USPTO) database, to map the possible bioactive compounds that may serve as potential future antimicrobial drugs. METHODS: A technological survey was carried out to verify existing patents using natural extracts with anti-biofilm potential. For this, it was searched with the keywords: Botanical extracts AND biofilms; which were performed in the United States Patent and Trademark Office (USPTO) database. Thus, the selected patent used a non-aqueous extract partitioned and vacuum-contracted, subsequently lyophilized for assays with antimicrobial potential. Because of this, a patent was analyzed regarding its chemistry, and biological activity, followed by a critical analysis of the technology proposed in the invention. RESULTS: When using the keywords Botanical extracts AND biofilms in the USPTO, it was possible to find twenty-two inventions; however, only four patents in the USPTO were in agreement with the proposal of the natural extract having antimicrobial activity and an anti-biofilm potential, of which two belonged to the same applicant with similar proposals. The key point of this invention was to enable the compounds of the Castanea sativa plant and its methods of obtaining the extract to present a significant antimicrobial action associated or not with antibiotics, promoting the development of new therapies against bacterial infections capable of disrupting biofilms. The invention developed a methodology for extracting Castanea sativa, in which pentacyclic triterpene compounds were found mostly in its leaves. Whereas for the extraction, the crude methanol extracts called extracts 224 from the ground leaves were made by maceration, filtered, combined, concentrated under pressure in rotary evaporators, and lyophilized. After that, they were resuspended in water and partitioned in succession with hexane, ethyl acetate, and butanol. The most active refined partition was the 224C extract with the solvent ethyl acetate, which was subjected to further fractionation using silica column chromatography. Resulting in the most refined extract, which was 224C-F2, capable of acting directly on the quorum sensing of bacteria, mainly Staphylococcus aureus, blocking the translation of RNAIII, including a series of exotoxins. Regarding the antimicrobial capacity against Staphylococcus aureus, it presented Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of 1.56 µg/mL-1 and > 100 µg/mL -1, respectively. CONCLUSION: Given the analyzed patent, it was possible to verify the importance of alternatives to reduce the impact of bacterial biofilms, which causes damage to industries in general and to health. From this, the invention analyzed has a promising proposal with antimicrobial potential focusing on the great impact of bacterial biofilms. Therefore, natural extracts with antibiofilmic potential can help to minimize the economic losses caused to health due to these multidrug-resistant microorganisms with different virulence mechanisms.

Infections in the first year after heart transplantation in a Latin American country.

BACKGROUND: Heart transplantation is the therapy of choice in patients with advanced heart failure refractory to other medical or surgical management. However, heart transplants are associated with complications that increase posttransplant morbidity and mortality. Infections are one of the most important complications after this procedure. Therefore, infections in the first year after heart transplantation were evaluated. METHODS: A retrospective cohort study of infections after heart transplants was conducted in a teaching hospital in Colombia between 2011 and 2019. Patients registered in the institutional heart transplant database (RETRAC) were included in the study. Microbiological isolates and infectious serological data were matched with the identities of heart transplant recipients and data from clinical records of individuals registered in the RETRAC were analyzed. The cumulative incidences of events according to the type of microorganism isolated were estimated using Kaplan-Meier survival analyses. RESULTS: Seventy-nine patients were included in the study. Median age was 49 years (37.4-56.3), and 26.58% of patients were women. Eighty-seven infections were documented, of which 55.17% (48) were bacterial, 22.99% (20) were viral, and 12.64% (11) were fungal. Bacterial infections predominated in the first month. In the first year, infections caused 38.96% of hospital admissions and were the second cause of death after heart transplants (25.0%). CONCLUSION: Posttransplant infections in the first year of follow-up were frequent. Bacterial infections predominated in the early posttransplant period. Infections, mainly bacterial, were the second most common cause of death and the most common cause of hospitalization in the first year after heart transplantation.

Deciphering the structure and mechanism of action of computer-designed mastoparan peptides.

Mastoparans are cationic peptides with multifunctional pharmacological properties. Mastoparan-R1 and mastoparan-R4 were computationally designed based on native mastoparan-L from wasps and have improved therapeutic potential for the control of bacterial infections. Here, we evaluated whether these peptides maintain their activity against Escherichia coli strains under a range of salt concentrations. We found that mastoparan-R1 and mastoparan-R4 preserved their activity under the conditions tested, including having antibacterial activities at physiological salt concentrations. The overall structure of the peptides was investigated using circular dichroism spectroscopy in a range of solvents. No significant changes in secondary structure were observed (random coil in aqueous solutions and α-helix in hydrophobic and anionic environments). The three-dimensional structures of mastoparan-R1 and mastoparan-R4 were elucidated through nuclear magnetic resonance spectroscopy, revealing amphipathic α-helical segments for Leu3-Ile13 (mastoparan-R1) and Leu3-Ile14 (mastoparan-R4). Possible membrane-association mechanisms for mastoparan-R1 and mastoparan-R4 were investigated through surface plasmon resonance and leakage studies with synthetic POPC and POPC/POPG (4:1) lipid bilayers. Mastoparan-L had the highest affinity for both membrane systems, whereas the two analogs had weaker association, but improved selectivity for lysing anionic membranes. This finding was also supported by molecular dynamics simulations, in which mastoparan-R1 and mastoparan-R4 were found to have greater interactions with bacteria-like membranes compared with model mammalian membranes. Despite having a few differences in their functional and structural profiles, the mastoparan-R1 analog stood out with the highest activity, greater bacteriostatic potential, and selectivity for lysing anionic membranes. This study reinforces the potential of mastoparan-R1 as a drug candidate.

Main Pathogens Causing Infections and Antibiotic Resistance Profile in Major Burns in Brazil Comparing Two Periods: 2015/2016 and 2019/2020.

Sepsis is the main cause of death in major burns. In this retrospective study conducted in a reference hospital in Brazil, the main agents causing infection and the resistance profile to antibiotics were identified. In addition, the epidemiological profile, length of hospital stay, type of burn, and total body surface area (TBSA) in major burns were collected from medical records, comparing the years 2015/2016 and 2019/2020. In both time periods, there was a predominance of males with a mean age of 43 years. Burns with less than 30% of TBSA predominated. There was a significant increase in positive cultures (P = .00026), from 58.7% to 80%, and an increase in skin punch culture collection from 25.6% to 43.9% in the years 2019/2020. The predominant etiological agent was Pseudomonas aeruginosa, followed by Acinetobacter baumannii resistant to carbapenems, and Staphylococcus aureus in both evaluated periods. The percentage of deaths was higher in 2019/2020 (26.2% vs. 14.6%; P = .026). The length of hospital stay was shorter in the latter period (P = .0081). Sepsis was the cause of death in 81.2% of cases in 2015/2020 and 78.3% in 2019/2020. Among the deaths, P. aeruginosa was the main agent identified. There was no change in the main pathogens and bacterial antibiotic resistance between the 2 time periods.

Bothrops snake venom L-amino acid oxidases impair biofilm formation of clinically relevant bacteria.

The present work addressed the abilities of two L-amino acid oxidases isolated from Bothrops moojeni (BmooLAAO-I) and Bothrops jararacussu (BjussuLAAO-II) snake venoms to control the growth and prevent the biofilm formation of clinically relevant bacterial pathogens. Upon S. aureus (ATCC BAA44) and S. aureus (clinical isolates), BmooLAAO-I (MIC = 0.12 and 0.24 µg/mL, respectively) and BjussuLAAO-II (MIC = 0.15 µg/mL) showed a potent bacteriostatic effect. Against E. coli (ATCC BAA198) and E. coli (clinical isolates), BmooLAAO-I (MIC = 15.6 and 62.5 µg/mL, respectively) and BjussuLAAO-II (MIC = 4.88 and 9.76 µg/mL, respectively) presented a lower extent effect. Also, BmooLAAO-I (MICB50 = 0.195 µg/mL) and BjussuLAAO-II (MICB50 = 0.39 µg/mL) inhibited the biofilm formation of S. aureus (clinical isolates) in 88% and 89%, respectively, and in 89% and 53% of E. coli (clinical isolates). Moreover, scanning electron microscopy confirmed that the toxins affected bacterial morphology by increasing the roughness of the cell surface and inhibited the biofilm formation. Furthermore, analysis of the tridimensional structures of the toxins showed that the surface-charge distribution presents a remarkable positive region close to the glycosylation motif, which is more pronounced in BmooLAAO-I than BjussuLAAO-II. This region may assist the interaction with bacterial and biofilm surfaces. Collectively, our findings propose that venom-derived antibiofilm agents are promising biotechnological tools which could provide novel strategies for biofilm-associated infections.

What is the epidemiological profile of acute hand infections at a hospital in sao paulo? / Qual o perfil epidemiológico de infecções agudas na mão num hospital filantrópico de são paulo?

ABSTRACT Objective: To determine the epidemiological profile of patients treated at a philanthropic hospital specialized in Orthopedics and Traumatology, located in a significant urban center, and evaluate the efficacy of initial empirical antibiotic treatment. Methods: Patients diagnosed with hand infections from September 2020 to September 2022 were included, excluding cases related to open fractures or post-surgical infections and those with incomplete medical records. The chi-square test was performed using STATISTICA ® software to correlate various variables. Results: A total of 34 patients participated, including 24 men and 10 women, with an average age of 41.9 years. Most male patients had Diabetes Mellitus, HIV, and drug addiction, and they resided in urban areas. Half of the patients did not report any apparent trauma. The most common infectious agent was Staphylococcus aureus*. Nearly 62% of patients required a change in the initial antibiotic regimen, with Penicillin being the most frequently substituted medication. Beta-lactam antibiotics and Quinolones were the most effective. Conclusion: These results suggest the importance of carefully evaluating the epidemiological profile of patients with acute hand infections and improving initial empirical treatment to ensure appropriate and effective therapy. Level of Evidence IV, Cross-Sectional Observational Study.

RESUMO Objetivo: Determinar o perfil epidemiológico de pacientes atendidos em um hospital filantrópico referência em Ortopedia e Traumatologia localizado em um centro urbano importante, e avaliar a eficácia do tratamento antibiótico empírico inicial. Métodos: Foram incluídos pacientes com diagnóstico de infecção na mão, atendidos no período de setembro de 2020 a setembro de 2022, excluindo-se casos relacionados a fraturas expostas ou pós-cirúrgicas e aqueles com prontuários incompletos. Realizou-se o teste do qui-quadrado, utilizando o software STATISTICA ® para correlacionar diversas variáveis. Resultados: Participaram do estudo 34 pacientes, sendo 24 homens e 10 mulheres, com média de idade de 41,9 anos. A maioria era de homens, com alta incidência de diabetes mellitus, HIV e drogadição, que residiam em áreas livres. Metade não relatou trauma evidente. O agente infeccioso mais comum foi o Staphylococcus aureus. Aproximadamente 62% dos pacientes precisaram de troca do esquema inicial de antibióticos, sendo a penicilina o medicamento mais frequentemente substituído. Os antibióticos beta-lactâmicos e quinolonas foram os mais eficientes. Conclusão: Esses resultados sugerem a importância de avaliar cuidadosamente o perfil epidemiológico dos pacientes com infecções agudas na mão e aprimorar o tratamento empírico inicial para garantir uma terapia adequada e eficaz. Nível de Evidência IV, Estudo Observacional Transversal.

Identification and antimicrobial susceptibility profile of bacteria isolated from primary endodontic infections

Abstract This study aimed to identify and characterize the antimicrobial susceptibility profile of bacteria found in primary endodontic infections in the teeth of patients treated at the Dental Clinic of the University of Ribeirão Preto, São Paulo, Brazil. From September to December 2019, samples were obtained from 21 patients with primary endodontic infections. The collections were carried out in triplicate using paper cones placed close to the total length of the root canal. Bacterial isolation was performed in Brain Heart Infusion agar, Blood agar, and other selective culture media cultured at 37°C for up to 48 h under aerobiosis and microaerophilic conditions. The bacterial species were identified using the Vitek 2 automated system. The disk diffusion method on agar Müeller-Hinton was used to assess antimicrobial susceptibility with the recommended antimicrobials for each identified bacterial species. A total of 49 antibiotics were evaluated. Fifteen of the 21 samples collected showed bacterial growth, and 17 bacterial isolates were found. There were 10 different bacterial species identified: Enterococcus faecalis (four isolates), Streptococcus mitis/oralis (three isolates), Streptococcus anginosus (three isolates) being the most common, followed by Staphylococcus epidermidis, Enterococcus faecium, Streptococcus constellatus, Streptococcus alactolyticus, Enterobacter cloacae, Klebsiella variicola, and Providencia rettgeri (one isolate of each species). The analysis demonstrated significant susceptibility to most of the tested antibiotics. However, some Enterococcus isolates resisted the antibiotic's erythromycin, ciprofloxacin, and tetracycline. A Staphylococcus epidermidis isolate was characterized as multidrug-resistant. Five Streptococcus isolates were non-susceptible to all antibiotics tested.

Antibacterial and antifungal activity of curcumin and methylene blue associated with laser on bacterial and fungal strains

Objective:To analyze the effect of methylene blue and 10% curcumin in fungi and bacteria through an in vitrostudy using photodynamic therapy (PDT). Methods:Curcumin and methylene blue were photosensitized by a Photon Lase III laser applied for 90 s in a dark environment within a laminar flow chamber. Enterococcus faecalisand Candida albicans strains were cultured and standardized.Then, a minimum inhibitoryconcentration (MIC) assay was conducted for these photosensitizers, with concentration variations and incubation to evaluate their antimicrobial activity. Results:With PDT, Curcumin had significant antibacterial activity against E. faecalis (MIC = 250 µg/mL).In contrast, methylene blue had antibacterial activity against E. faecalis (MIC < 12.5 µg/mL with PDT) and antifungal activity against C. albicans (MIC <12.5 µg/mL with or without PDT).Both agents showed greater efficacy in the presence of the laser.The results suggest that curcumin and methylene blue associated with laser may effectively treat microbial infections. Conclusion:Further research is needed to evaluate the efficacy and safety of using these agents in animal and human models and theireffectiveness against different bacterial and fungal strains.

Asthma-associated bacterial infections: Are they protective or deleterious?

Eosinophilic, noneosinophilic, or mixed granulocytic inflammations are the hallmarks of asthma heterogeneity. Depending on the priming of lung immune and structural cells, subjects with asthma might generate immune responses that are TH2-prone or TH17-prone immune response. Bacterial infections caused by Haemophilus, Moraxella, or Streptococcus spp. induce the secretion of IL-17, which in turn recruit neutrophils into the airways. Clinical studies and experimental models of asthma indicated that neutrophil infiltration induces a specific phenotype of asthma, characterized by an impaired response to corticosteroid treatment. The understanding of pathways that regulate the TH17-neutrophils axis is critical to delineate and develop host-directed therapies that might control asthma and its exacerbation episodes that course with infectious comorbidities. In this review, we outline clinical and experimental studies on the role of airway epithelial cells, S100A9, and high mobility group box 1, which act in concert with the IL-17-neutrophil axis activated by bacterial infections, and are related with asthma that is difficult to treat. Furthermore, we report critically our view in the light of these findings in an attempt to stimulate further investigations and development of immunotherapies for the control of severe asthma.

Utilidad diagnóstica de los tiempos de positividad de hemocultivos para distinguir verdaderas bacteriemias de contaminantes en base a un sistema automatizado / Diagnostic performance of the time to positivity of blood cultures to distinguish true bacteremia from contaminants based on an automated system

RESUMEN Objetivo. Determinar la utilidad diagnóstica de los tiempos de positividad de hemocultivos para distinguir verdaderas bacteriemias de contaminantes en el sistema automatizado «BACT/ALERT®¼. Materiales y métodos. Se realizó un estudio transversal de tipo pruebas diagnósticas, a partir de una base de datos de muestras de hemocultivos procesadas entre enero del 2016 y agosto del 2021. Se incluyeron todas las muestras de hemocultivos de pacientes con sospecha de bacteriemia, las muestras de hemocultivos fueron ingresadas al sistema «BACT/ALERT®¼ para diferenciar verdaderas bacteriemias de contaminantes. Resultados. Se analizó un total de 33 951 frascos de hemocultivos y se obtuvieron 3875 frascos positivos. El 75,2% (n=2913) del total de hemocultivos positivos fueron verdaderas bacteriemias y 24,8% (n=962) fueron contaminantes. La mediana de tiempo de positividad en los hemocultivos con verdaderas bacteriemias fue significativamente menor (16,3 horas; RIC: 11,2 - 24,9) que la mediana de tiempo de positividad de hemocultivos con contaminantes (22,5 horas; RIC: 18,4 - 31,8; p<0,001). El tiempo de positividad demostró capacidad discriminante para diferenciar verdaderas bacteriemias de contaminantes, con un AUC-ROC de 0,73 (IC95%: 0,71 - 0,75), con 85% y 63% de sensibilidad y especificidad respectivamente para el diagnóstico de contaminantes cuando el tiempo de positividad supera las 16,5 horas. La administración de antibióticos previos a la toma retrasó el tiempo de positividad, en cambio, haber presentado fiebre antes de la toma de muestra acortó el tiempo de positividad. Conclusiones. Nuestros resultados muestran un buen desempeño de los tiempos de positividad de hemocultivos para diferenciar verdaderas bacteriemias de contaminantes utilizando el sistema «BACT/ALERT®¼ cuando el tiempo de positividad fue superior a 16,5 horas.

ABSTRACT Objective. To determine the diagnostic performance of blood culture positivity times for distinguishing true bacteremia from contaminants in the automated "BACT/ALERT®" system. Materials and methods. A cross-sectional, diagnostic test-type study was conducted from a database of blood culture samples processed between January 2016 and August 2021. All blood culture samples from patients with suspected bacteremia were included; blood culture samples were entered into the "BACT/ALERT®" system to differentiate true bacteremia from contaminants. Results. We obtained 33,951 blood cultures samples, of which 3875 were positive. Of the total number of positive blood cultures, 75.2% (n=2913) were true bacteremia and 24.8% (n=962) were contaminants. The median time to positivity in blood cultures with true bacteremia was significantly shorter (16.3 hours; IQR: 11.2 - 24.9) than the median time to positivity of blood cultures with contaminants (22.5 hours; IQR: 18.4 - 31.8; p<0.001). The positivity time showed the capacity to differentiate true bacteremia from contaminants, with an AUC-ROC of 0.73 (95%CI: 0.71 - 0.75), with 85% and 63% sensitivity and specificity respectively for the diagnosis of contaminants when the positivity time exceeds 16.5 hours. The use of antibiotics prior to sampling delayed the time to positivity, while having fever before sampling shortened the time to positivity. Conclusions. Our results show good diagnostic performance of blood culture positivity times to differentiate true bacteremia from contaminants using the "BACT/ALERT®" system when the positivity time was longer than 16.5 hours.

ShlA toxin of Serratia induces P2Y2- and α5ß1-dependent autophagy and bacterial clearance from host cells.

Serratia marcescens is an opportunistic human pathogen involved in antibiotic-resistant hospital acquired infections. Upon contact with the host epithelial cell and prior to internalization, Serratia induces an early autophagic response that is entirely dependent on the ShlA toxin. Once Serratia invades the eukaryotic cell and multiples inside an intracellular vacuole, ShlA expression also promotes an exocytic event that allows bacterial egress from the host cell without compromising its integrity. Several toxins, including ShlA, were shown to induce ATP efflux from eukaryotic cells. Here, we demonstrate that ShlA triggered a nonlytic release of ATP from Chinese hamster ovary (CHO) cells. Enzymatic removal of accumulated extracellular ATP (eATP) or pharmacological blockage of the eATP-P2Y2 purinergic receptor inhibited the ShlA-promoted autophagic response in CHO cells. Despite the intrinsic ecto-ATPase activity of CHO cells, the effective concentration and kinetic profile of eATP was consistent with the established affinity of the P2Y2 receptor and the known kinetics of autophagy induction. Moreover, eATP removal or P2Y2 receptor inhibition also suppressed the ShlA-induced exocytic expulsion of the bacteria from the host cell. Blocking α5ß1 integrin highly inhibited ShlA-dependent autophagy, a result consistent with α5ß1 transactivation by the P2Y2 receptor. In sum, eATP operates as the key signaling molecule that allows the eukaryotic cell to detect the challenge imposed by the contact with the ShlA toxin. Stimulation of P2Y2-dependent pathways evokes the activation of a defensive response to counteract cell damage and promotes the nonlytic clearance of the pathogen from the infected cell.