Antifungal activity of Caryocar brasiliense camb. Alone or along with antifungal agents against multidrug-resistant Candida auris.

ETHNOPHARMACOLOGICAL RELEVANCE: Candida auris poses a severe global health threat, with many strains resistant to antifungal treatments, complicating therapy. Exploring natural compounds alongside conventional drugs offers promising therapeutic avenues. The antifungal potential of the ethanolic extract from Caryocar brasiliense (Cb-EE), a plant native to the Brazilian cerrado and renowned for its medicinal properties, was investigated against C. auris. AIM OF THE STUDY: The study examined the chemical composition, antifungal activity, mechanisms of action, and in vivo effects of Cb-EE. MATERIALS AND METHODS: Leaves of C. brasiliense were processed to extract ethanolic extract, which was evaluated for phenolic compounds, flavonoids, and tannins. The antifungal capacity was determined through broth microdilution and checkerboard methods, assessing interaction with conventional antifungals. RESULTS: Cb-EE demonstrated fungistatic activity against various Candida species and Cryptococcus neoformans. Synergy with fluconazole and additive effects with other drugs were observed. Cb-EE inhibited C. auris growth, with the combination of fluconazole extending inhibition. Mechanistic studies revealed interference with fungal membranes, confirmed by sorbitol protection assays, cellular permeability tests, and scanning electron microscopy (SEM). Hemocompatibility and in vivo toxicity tests on Tenebrio molitor showed safety. CONCLUSION: Cb-EE, alone or in combination with fluconazole, effectively treated C. auris infections in vitro and in vivo, suggesting its prospective role as an antifungal agent against this emerging pathogen.

CARD9 mutations in patients with fungal infections: An update from the last 5 years.

BACKGROUND: Autosomal recessive deficiency in the caspase recruitment domain-containing protein 9 (CARD9) is a congenital immunological condition that leads to susceptibility to mucocutaneous and invasive fungal infections. There is growing incidence of fungal infections in patients with CARD9 deficiency, a phenomenon that is increasingly recognised. OBJECTIVES: This study aimed to assess the frequency, geographic distribution and nature of mutations in patients with CARD9 deficiency, based on published papers in the literature until March 2023. METHODS: We swiftly conducted a study to pinpoint every documented instance of fungal infections arising from CARD9 deficiency. We selected case reports from the databases of PubMed, Embase, Scopus and Google Scholar spanning the period from October 2009 to March 2023. RESULTS: We analysed 90 cases of fungal infections and identified 32 mutations in the CARD9 gene. Notably, the homozygous (HMZ) p.Q295X (c.883C > T) mutation was associated with an increased risk of candidiasis. In contrast, the HMZ p.Q289X (c.865C > T) mutation is linked to a higher risk of dermatophytosis. We observed differences in the geographical distribution of these mutations. The primary mutations found in African patients differ from those in Asian patients. Specifically, Asian patients exhibit a broader spectrum of CARD9 mutations than African patients. CONCLUSIONS: The diversity of mutations observed in the 90 cases revealed 32 distinct variations, emphasising the unique genetic alterations in the CARD9 gene associated with specific geographical areas and the corresponding prevalence of fungal infections.

Synergistic interaction of polymyxin B with carvacrol: antimicrobial strategy against polymyxin-resistant Klebsiella pneumoniae.

Objective: The antimicrobial activities of the synergistic combination of carvacrol and polymyxin B against polymyxin-resistant Klebsiella pneumoniae were evaluated. Methods: The methods employed checkerboard assays to investigate synergism, biofilm inhibition assessment and membrane integrity assay. In addition, the study included in vivo evaluation using a mouse infection model. Results: The checkerboard method evaluated 48 combinations, with 23 indicating synergistic action. Among these, carvacrol 10 mg/kg plus polymyxin B 2 mg/kg exhibited in vivo antimicrobial activity in a mouse model of infection, resulting in increased survival and a significant decrease in bacterial load in the blood. Conclusion: Polymyxin in synergy with carvacrol represents a promising alternative to be explored in the development of new antimicrobials.

In this study, we wanted to find a new way to fight a bacteria called Klebsiella pneumoniae, which is not easily killed by medication. We mixed two drugs, carvacrol and polymyxin B, to see if they would work together to fight the bacteria. We found that the mixed treatment helped to kill the bacteria. We also tried this mixed treatment in sick mice, and they got better. Our study shows that this mixed treatment might be a new way to fight bacteria that are hard to kill with regular drugs. Next, we hope to learn more about how it works.

Fusariosis in burn patients: A systematic review of case reports.

Burns can cause skin damage, facilitating the entry of fungi and other microorganisms into the body, leading to infections. Fusarium is a fungus capable of infecting individuals with burn injuries. Diagnosing and treating Fusarium infections in burn patients can be challenging due to the manifestation of nonspecific symptoms. This study aims to investigate case reports and case series from published literature describing Fusarium infection in burned patients, in order to assess treatment regimens, clinical outcomes, and make recommendations for future management. We conducted searches on Web of Science, PubMed, ScienceDirect, and Medline for all case reports and case series containing keywords 'Burn', 'Burns', 'Burned', 'Fusarium', or 'Fusariosis' in the title or abstract. All burn patients who developed Fusarium fungal infections between January 1974 and March 2023 were included in the study. Demographic and clinical data were analyzed retrospectivity. The final analysis incorporates 24 case reports encompassing a total of 87 burn patients with Fusarium infection. Patient ages ranged from one to 85 years, with the majority being male (53%). The median percentage of burn surface area was 78%, and the skin in the face, upper limbs, and lower limbs were the most commonly infected sites. Fungal infections appeared around 10 days after the burn injury on average. The majority of the patients were identified through culture or histopathology. The Fusarium dimerum species complex, which was found in nine patients, was the most frequently identified Fusarium species complex. Amphotericin B was the most preferred treatment drug, followed by voriconazole, and 62% of patients underwent debridement. In our study, 23 patients (37%) died from fungal infections. Implementing early and effective treatment protocols targeting Fusarium spp. in burn treatment units can significantly reduce mortality rates. It is critical to enhance the understanding of fusariosis epidemiology and emphasize the importance of maintaining a high clinical suspicion for this condition in burn patients.

Pediatric mucormycosis associated with COVID-19: A systematic review of clinical cases.

The occurrence of mucormycosis has been observed in individuals with COVID-19. However, there is limited information on the epidemiological factors, presentation, diagnostic certainty, and outcome of this infection in children. PubMed, MEDLINE, Scopus, Embase, Web of Science, LitCovid, and back-references of the identified manuscripts were systematically searched from December 2019 to March 2023. We have identified 14 cases of pediatric mucormycosis in patients with COVID-19. The median age of patients was 10.7 years. Among these cases, 10 were associated with active COVID-19. In 7 cases, the patients had pre-existing diabetes mellitus and concomitant diabetic ketoacidosis. Corticosteroids were administered to treat COVID-19 in 7 of the patients. The most common clinical presentation of the disease was rhino-orbital cerebral mucormycosis. Seven patients died (50%). Given the high mortality rate, clinicians should maintain a high level of clinical suspicion of mucormycosis in pediatric patients with COVID-19.

Impact of COVID-19 pandemic in the Brazilian maternal mortality ratio: A comparative analysis of Neural Networks Autoregression, Holt-Winters exponential smoothing, and Autoregressive Integrated Moving Average models.

BACKGROUND AND OBJECTIVES: The acute respiratory infection caused by severe acute respiratory syndrome coronavirus disease (COVID-19) has resulted in increased mortality among pregnant, puerperal, and neonates. Brazil has the highest number of maternal deaths and a distressing fatality rate of 7.2%, more than double the country's current mortality rate of 2.8%. This study investigates the impact of the COVID-19 pandemic on the Brazilian Maternal Mortality Ratio (BMMR) and forecasts the BMMR up to 2025. METHODS: To assess the impact of the COVID-19 pandemic on the BMMR, we employed Holt-Winters, Autoregressive Integrated Moving Average (ARIMA), and Neural Networks Autoregression (NNA). We utilized a retrospective time series spanning twenty-five years (1996-2021) to forecast the BMMR under both a COVID-19 pandemic scenario and a controlled COVID-19 scenario. RESULTS: Brazil consistently exhibited high maternal mortality values (mean BMMR [1996-2019] = 57.99 ±6.34/100,000 live births) according to World Health Organization criteria. The country experienced its highest mortality peak in the historical BMMR series in the second quarter of 2021 (197.75/100,000 live births), representing a more than 200% increase compared to the previous period. Holt-Winter and ARIMA models demonstrated better agreement with prediction results beyond the sample data, although NNA provided a better fit to previous data. CONCLUSIONS: Our study revealed an increase in BMMR and its temporal correlation with COVID-19 incidence. Additionally, it showed that Holt-Winter and ARIMA models can be employed for BMMR forecasting with lower errors. This information can assist governments and public health agencies in making timely and informed decisions.

Neurosyphilis in pediatric population: a review of cases / Neurossífilis na população pediátrica: revisão de casos / Neurosífilis en población pediátrica: revisión de casos

Background: Neurosyphilis is the most severe presentation of acquired and congenital syphilis, it occurs when Treponema pallidum penetrates the central nervous system. This development can occur at any time during the evolution of the disease phases. In Brazil in 2021, 2,343 children born with congenital syphilis were diagnosed with neurosyphilis, representing 9.3% of the total. The objective of this study was to analyze the scientific evidence on the medical manifestations presented by pediatric patients affected by neurosyphilis. Methods: In February 2023, PubMed, VHL, Scopus, Lilacs and Bdenf databases were researched for published case reports of patients aged zero to less than 18 years with T. pallidum infection. The data analysis period covered 55 years. Results: Nine articles were found in the period of publication from 1967 to 2022. There were two cases in females and only one with manifestation in an adolescent of acquired neurosyphilis. The adolescent's case was the only one with a favorable outcome after adequate treatment. Other cases resulted in impaired quality of life for patients and family members involved in child care. Conclusion: The reported cases of neurosyphilis were mostly related to late diagnosis. Evidencing the fragility of prenatal care, which is crucial for prevention and intervention by T. pallidum infection causes serious consequences for child development. Therefore, control measures should focus on mandatory prenatal screening during the first trimester of pregnancy, partner notification, prompt treatment and postnatal follow-up of the newborn.

Introdução: A neurossífilis é a apresentação mais grave da sífilis adquirida e congênita, ocorre quando o Treponema pallidum penetra no sistema nervoso central. Esse desenvolvimento pode ocorrer a qualquer momento durante a evolução das fases da doença. No Brasil, em 2021, 2.343 crianças nascidas com sífilis congênita foram diagnosticadas com neurossífilis, representando 9,3% do total. O objetivo deste estudo foi analisar as evidências científicas sobre as manifestações clínicas apresentadas por pacientes pediátricos acometidos por neurossífilis. Métodos: Em fevereiro de 2023, os bancos de dados PubMed, BVS, Scopus, Lilacs e Bdenf foram pesquisados para relatos de casos publicados de pacientes de zero a menos de 18 anos com infecção por T. pallidum. O período de análise dos dados abrangeu 55 anos. Resultados: Foram encontrados nove artigos no período de publicação de 1967 a 2022. Houve dois casos no sexo feminino e apenas um com manifestação em adolescente de neurossífilis adquirida. O caso da adolescente foi o único com evolução favorável após tratamento adequado. Outros casos resultaram em comprometimento da qualidade de vida dos pacientes e familiares envolvidos no cuidado da criança. Conclusão: Os casos notificados de neurossífilis foram, em sua maioria, relacionados ao diagnóstico tardio. Evidenciando a fragilidade do pré-natal, fundamental para a prevenção e intervenção da infecção pelo T. pallidum, trazendo sérias consequências para o desenvolvimento infantil. Portanto, as medidas de controle devem se concentrar na triagem pré-natal obrigatória durante o primeiro trimestre de gravidez, notificação do parceiro, tratamento imediato e acompanhamento pós-natal do recém-nascido.

Introducción: La neurosífilis es la presentación más grave de la sífilis adquirida y congénita, se presenta cuando Treponema pallidum penetra al sistema nervioso central. Este desarrollo puede ocurrir en cualquier momento durante la evolución de las fases de la enfermedad. En Brasil, en 2021, 2.343 niños nacidos con sífilis congénita fueron diagnosticados con neurosífilis, lo que representa el 9,3% del total. El objetivo de este estudio fue analizar la evidencia científica sobre las manifestaciones médicas que presentan los pacientes pediátricos afectados por neurosífilis. Métodos: en febrero de 2023, se investigaron las bases de datos PubMed, VHL, Scopus, Lilacs y Bdenf para obtener informes de casos publicados de pacientes de cero a menos de 18 años con infección por T. pallidum. El período de análisis de los datos abarcó 55 años. Resultados: Se encontraron nueve artículos en el período de publicación de 1967 a 2022. Hubo dos casos en el sexo femenino y solo uno con manifestación en un adolescente de neurosífilis adquirida. El caso de la adolescente fue el único con evolución favorable luego de un tratamiento adecuado. Otros casos resultaron en deterioro de la calidad de vida de los pacientes y familiares involucrados en el cuidado de niños. Conclusión: Los casos notificados de neurosífilis se relacionaron en su mayoría con un diagnóstico tardío. Evidenciando la fragilidad del control prenatal, que es fundamental para la prevención e intervención de la infección por T. pallidum que provoca graves consecuencias para el desarrollo infantil. Por lo tanto, las medidas de control deben centrarse en el tamizaje prenatal obligatorio durante el primer trimestre del embarazo, la notificación a la pareja, el tratamiento oportuno y el seguimiento posnatal del lactante.

Determining reference ranges for immunological cells of healthy indigenous individuals from a region in Brazil.

Morais et al. conducted a pioneering study with Brazilian indigenous populations to determine reference values for immunologic cells from healthy adult individuals. The main findings included a higher relative median for T lymphocyte subsets in females than males, and T CD3+, T CD4+, and T CD8+ relative values were statistically different when compared with Brazilian populations from other Brazilian regions. The relative medians of CD3+, CD4+, and CD8+ T cells were significantly higher in women than in men in a healthy indigenous population. Demographic and ethnic diversity of the Brazilian population can be associated with quantitative modifications in the immunologic cells of healthy individuals. OBJECTIVE: The establishment of reference values for a subset of leukocytes is common in clinical practice, and ethnic variations are strongly associated with disease development. In Brazil, indigenous people are vulnerable to infections, and few studies have described the health and disease conditions of this population. This study aimed to provide reference values for immunological cell subsets in indigenous Brazilians living in the state of Mato Grosso do Sul. METHODS: Flow cytometry and 4-color combinations of monoclonal antibodies were used to characterize cells. A total of 115 healthy adults, mostly females (72%), were included in the study. The results are presented as mean and median (2.5%-97.5% percentiles) for T and B lymphocytes, CD4+ T cells, CD8+ T cells, Natural Killer cells, monocytes, and dendritic cells, providing an average immunological profile for the population in question. RESULTS: The relative medians of CD3+, CD4+, and CD8+ T cells were significantly higher in women than in men in a healthy indigenous population. CONCLUSION: To our knowledge, cell reference data from indigenous Brazilians are unknown in the literature. The immune cell results presented in this pioneering study will contribute to the clinical and laboratory evaluation of the Brazilian indigenous population, especially given the important differences when compared with other Brazilian ethnic groups.

Synergy between amikacin and Protium heptaphyllum essential oil against polymyxin resistance Klebsiella pneumoniae.

AIMS: We investigated the chemical composition and the in vitro and in vivo antibacterial effects of Protium heptaphyllum essential oil (PHEO) alone and in combination with antibiotics against polymyxin-resistant Klebsiella pneumoniae isolates. METHODS AND RESULTS: Hydrodistillation was used to obtain PHEO, and gas chromatography coupled with mass spectrometry revealed α-pinene, δ-3-carene, and ß-pinene as major components present in PHEO. Minimum inhibitory concentration was determined using the broth microdilution technique and ranged from 256 to 512 µg ml-1. The checkerboard method showed synergy with the combination of PHEO and amikacin (AMK) against the polymyxin-resistant K. pneumoniae isolates. In 8 of the 10 isolates tested, the fractional inhibitory concentration indexes (FICIs) ranged from 0.06 to 0.5, while in the remaining two isolates, the combination exerted an additive effect (FICI of 0.6 and 1.0), resulting in AMK dose reduce of range 2- to 16-fold, in the presence of PHEO. Analysis using zero interaction potency revealed high synergy score (63.9). In the in vivo assay, the survival of Caenorhabditis elegans was significantly improved in the presence of PHEO (1 µg ml-1) + AMK (µg ml-1) combination as compared to 32 µg ml-1 AMK alone. Furthermore, PHEO concentrations of 256 and 512 µg ml-1 were found to be non-toxic on the experimental model. CONCLUSION: To our knowledge, this is the first report of such type of synergism demonstrating an antimicrobial effect against polymyxin-resistant K. pneumoniae isolates.

How Did COVID-19 Impact the Antimicrobial Consumption and Bacterial Resistance Profiles in Brazil?

The indiscriminate use of antibiotics has favored the selective pressure of multidrug resistance among microorganisms. This research evaluated the pattern of antibiotic prescriptions among the Brazilian population between January 2018 and December 2021. Additionally, the study sought to analyze the incidence rates of central line-associated bloodstream infection (CLABSI) and examine the profiles of antibiotic resistance. We assessed the hospital and community antimicrobial consumption from the National Health Surveillance Agency Database and correlated it to microorganisms. The consumption of antimicrobials in the hospital environment increased by 26% in 2021, highlighting polymyxin B, which increased by 204%. In 2021, 244,266 cases of CLABSI were reported, indicating a nosocomial infection rate of 7.9%. The rate of resistance to polymyxin B was higher in Pseudomonas aeruginosa (1400%) and Klebsiella pneumoniae (514%). Azithromycin emerged as the predominant antibiotic utilized within the community setting, accounting for 24% of the overall consumption. Pearson's correlation analysis revealed a significant and positive correlation (r = 0.71) between the elevated usage of azithromycin and the incidence of COVID-19. Our results indicate an increase in antimicrobial consumption during the COVID-19 pandemic and reinforce the fact that the misuse of antimicrobials may lead to an expansion in antimicrobial resistance.

Sporotrichosis co-infection with human immunodeficiency virus/acquired immunodeficiency syndrome.

Sporotrichosis is a subcutaneous mycosis caused by a dimorphic fungus belonging to the genus Sporothrix. This fungal infection can affect both humans and domestic animals, and in recent years, an increase in the geographic spread and prevalence of sporotrichosis has been observed globally. This systematic review aimed to examine the clinical-epidemiological and therapeutic aspects related to sporotrichosis co-infection with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). An extensive electronic search was conducted on databases including PubMed, Web of Science, Lilacs, Medline, Embase, Scopus and SciELO was performed to identify clinical cases of people living with HIV (PLWH) with sporotrichosis published until May 2023. As a result, we found that most co-infected patients were male, representing 71.76% (94/131) of cases. The most prevalent age group was 41-50 years, with a mean age of 36.98 years. The countries with the highest number of cases were Brazil (75.57%, 99/131) and the United States (16.03%, 21/131). The most frequent clinical presentation was systemic dissemination, accounting for 69.47% (91/131) of the cases, followed by cutaneous dissemination with 13% (17/131). The mean CD4+ cell count was 154.07 cells/µL, and most patients used amphotericin B with at least one azole, which represented 47.33% (62/131) of cases, followed by azole monotherapy in 17.56% (23/131) of cases. As for the outcome, 51.15% (67/131) of the patients remained alive, and 37.4% (49/131) died. Therefore, it was concluded that sporotrichosis in PLWH is a disease with a high prevalence in Brazil and may be associated with systemic clinical manifestations requiring longer periods of systemic antifungal therapy.

Multidrug-resistant gram-negative bacteria in patients with COVID-19: An epidemiological and clinical study.

Epidemiological data regarding the incidence of secondary multidrug-resistant (MDR) Gram-negative infection in patients with coronavirus disease (COVID-19) in Brazil are still ambiguous. Thus, a case-control study was designed to determine factors associated with the acquisition of MDR Gram-negative bacteria (GNB) in patients with and without COVID-19 and describe the mortality rates and clinical features associated with unfavorable outcomes. In total, we assessed 280 patients admitted to Brazilian intensive care units from March/2020 to December/2021. During the study, 926 GNB were isolated. Out of those, 504 were MDR-GNB, representing 54.4% of the resistance rate. In addition, out of 871 patients positive for COVID-19, 73 had secondary MDR-GNB infection, which represented 8.38% of documented community-acquired GNB-MDR infections. The factors associated with patients COVID-19-MDR-GNB infections were obesity, heart failure, use of mechanical ventilation, urinary catheter, and previous use of ß-lactams. Several factors associated with mortality were identified among patients with COVID-19 infected with MDR-GNB, including the use of a urinary catheter; renal failure; and the origin of bacterial cultures such as tracheal secretion, exposure to carbapenem antibiotics, and polymyxin. Mortality was significantly higher in patients with COVID-19-MDR-GNB (68.6%) compared to control groups, where COVID-19 was 35.7%, MDR-GNB was 50%, and GNB was 21.4%. Our findings demonstrate that MDR-GNB infection associated with COVID-19 has an expressive impact on increasing the case fatality rate, reinforcing the importance of minimizing the use of invasive devices and prior exposure to antimicrobials to control the bacterial spread in healthcare environments to improve the prognosis among critical patients.

Evaluation of the Synthetic Multifunctional Peptide Hp-MAP3 Derivative of Temporin-PTa.

In recent years, antimicrobial peptides isolated from amphibian toxins have gained attention as new multifunctional drugs interacting with different molecular targets. We aimed to rationally design a new peptide from temporin-PTa. Hp-MAP3 (NH2-LLKKVLALLKKVL-COOH), net charge (+4), hydrophobicity (0.69), the content of hydrophobic residues (69%), and hydrophobic moment (0.73). For the construction of the analog peptide, the physicochemical characteristics were reorganized into hydrophilic and hydrophobic residues with the addition of lysines and leucines. The minimum inhibitory concentration was 2.7 to 43 µM against the growth of Gram-negative and positive bacteria, and the potential for biofilm eradication was 173.2 µM. Within 20 min, the peptide Hp-MAP3 (10.8 µM) prompted 100% of the damage to E. coli cells. At 43.3 µM, eliminated 100% of S. aureus within 5 min. The effects against yeast species of the Candida genus ranged from 5.4 to 86.6 µM. Hp-MAP3 presents cytotoxic activity against tumor HeLa at a concentration of 21.6 µM with an IC50 of 10.4 µM. Furthermore, the peptide showed hemolytic activity against murine erythrocytes. Structural studies carried out by circular dichroism showed that Hp-MAP3, while in the presence of 50% trifluoroethanol or SDS, an α-helix secondary structure. Finally, Amphipathic Hp-MAP3 building an important model for the design of new multifunctional molecules.

Antimicrobial peptides against polymyxin-resistant Klebsiella pneumoniae: a patent review.

The spread of polymyxin-resistant Klebsiella pneumoniae strains represents an emerging health challenge, limiting treatment options for the patients. Thus, the development of new antimicrobials is an urgent requirement. Antimicrobial peptides (AMPs) are a large class of compounds that are part of innate immune response; these peptides are promising compounds in the field of antimicrobial resistance and are present in all organisms. The present review evaluated patents on antimicrobial peptides tested against polymyxin-resistant K. pneumoniae, available on Espacenet as of September 2022. A total of 1313 patents were examined and 1197 excluded as they were out of focus for this review; 104 patents of peptides tested against K. pneumoniae were included; of which only 14 were tested against polymyxin-resistant K. pneumoniae strains. The results indicated that all AMPs evaluated were in the experimental or pre-clinical phase; the clinical phase is pending. Furthermore, a few peptides were tested effectively against polymyxin-resistant K. pneumoniae. Although, the research and patent filing alone are not enough to develop a suitable antimicrobial therapy, they can represent good starting point upon which to develop new antimicrobials. More investment is required to push these pharmaceuticals through the stages of development to introduce them into the market.

Antimicrobial and antibiofilm activities of desloratadine against multidrug-resistant Acinetobacter baumannii.

Aim: The antimicrobial and antibiofilm activities of the antihistamine desloratadine against multidrug-resistant (MDR) Acinetobacter baumannii were evaluated. Results: Desloratadine inhibited 90% bacterial growth at a concentration of 64 µg/ml. The combination of desloratadine with meropenem reduced the MIC by twofold in the planktonic state and increased the antibiofilm activity by eightfold. Survival curves showed that combinations of these drugs were successful in eradicating all bacterial cells within 16 h. Scanning electron microscopy also confirmed a synergistic effect in imparting a harmful effect on the cellular structure of MDR A. baumannii. An in vivo model showed significant protection of up to 83% of Caenorhabditis elegans infected with MDR A. baumannii. Conclusion: Our results indicate that repositioning of desloratadine may be a safe and low-cost alternative as an antimicrobial and antibiofilm agent for the treatment of MDR A. baumannii infections.

Determining reference ranges for immunological cells of healthy indigenous individuals from a region in Brazil

ABSTRACT Objective The establishment of reference values for a subset of leukocytes is common in clinical practice, and ethnic variations are strongly associated with disease development. In Brazil, indigenous people are vulnerable to infections, and few studies have described the health and disease conditions of this population. This study aimed to provide reference values for immunological cell subsets in indigenous Brazilians living in the state of Mato Grosso do Sul. Methods Flow cytometry and 4-color combinations of monoclonal antibodies were used to characterize cells. A total of 115 healthy adults, mostly females (72%), were included in the study. The results are presented as mean and median (2.5%-97.5% percentiles) for T and B lymphocytes, CD4+ T cells, CD8+ T cells, Natural Killer cells, monocytes, and dendritic cells, providing an average immunological profile for the population in question. Results The relative medians of CD3+, CD4+, and CD8+ T cells were significantly higher in women than in men in a healthy indigenous population. Conclusion To our knowledge, cell reference data from indigenous Brazilians are unknown in the literature. The immune cell results presented in this pioneering study will contribute to the clinical and laboratory evaluation of the Brazilian indigenous population, especially given the important differences when compared with other Brazilian ethnic groups.

New Technologies to Diagnose and Treat a Multidrug-Resistant Candida auris: A Patent Review.

Candida auris is responsible for hospital outbreaks worldwide. Some C. auris isolates may show concomitant resistance to azoles, echinocandins, and polyenes, thereby possibly leaving clinicians with few therapeutic options. In addition, this multi-drug-resistant yeast is difficult to identify with conventional methods and has the ability to persist on environmental surfaces causing hospital-acquired infections. The development of new treatment options and tools for identification is critical to control, prevent, and establish an early diagnosis of this emerging pathogen. The aim of this study was to perform a critical patent review to explore and identify the latest advances in therapeutic strategies as well as diagnostic methods for C. auris. A total of 19 patents were identified for a preliminary assessment from the Espacenet database. Three patents were excluded as they were out of focus for this review according to their abstract and/or description. The final selection covered 16 patents, which were surveyed by country, year and classified as treatment or diagnostic methods for C. auris. As noted in the patent reading, in recent years, the interest of academic, government and industry sectors have shown an increasing tendency focused on research and development of new therapeutic molecules and diagnostic methods to combat this emerging pathogen.

What do we have that is new in antifungal peptides? A patent review.

Drugs used to fight fungal infections may cause toxic or adverse drug interactions. For this reason, there is an increase in the development of natural, semisynthetic and synthetic antifungal peptides. This study aimed to perform a patent review to identify the advances in peptides to treat fungal infections. In a preliminary assessment, 597 patents were identified from the database. Then, duplicated patents (62) and those with titles in disagreement with the scope of this review (196) were excluded. Then, six patents were not in English or Spanish. Following the screening, 288 patents were outside the focus of this review, according to their abstract and description. The final selection covered 45 patents.

Currently, medications used to treat fungal infections may interact negatively with other drugs or be hazardous to the host. Scientists have been looking for novel, safe and efficient antifungal drugs since the enhancement of fungal resistance. Antimicrobial peptides, as opposed to traditional antibiotics, offer a variety of antibacterial activity against bacteria, fungi, parasites, viruses and cancer cells. The production of isolated natural, semisynthetic and synthetic antifungal peptides has increased. As a result, patents are a reliable and up-to-date source of innovation. As a result, their content analysis provides crucial information for identifying trends in new medications and targeted treatment plans.

Genetic Diversity of Virulent Polymyxin-Resistant Klebsiella aerogenes Isolated from Intensive Care Units.

This study evaluated the scope and genetic basis of polymyxin-resistant Klebsiella aerogenes in Brazil. Eight polymyxin-resistant and carbapenemase-producing K. aerogenes strains were isolated from patients admitted to the ICU of a tertiary hospital. Bacterial species were identified by automated systems and antimicrobial susceptibility profile was confirmed using broth microdilution. The strains displayed a multidrug resistant profile and were subjected to whole-genome sequencing. Bioinformatic analysis revealed a variety of antimicrobial resistance genes, including the blaKPC-2. No plasmid-mediated colistin resistance gene was identified. Nonetheless, nonsynonymous mutations in mgrB, pmrA, pmrB, and eptA were detected, justifying the colistin resistance phenotype. Virulence genes encoding yersiniabactin, colibactin, and aerobactin were also found, associated with ICEKp4 and ICEKp10, and might be related to the high mortality observed among the patients. In fact, this is the first time ICEKp is identified in K. aerogenes in Brazil. Phylogenetic analysis grouped the strains into two clonal groups, belonging to ST93 and ST16. In summary, the co-existence of antimicrobial resistance and virulence factors is deeply worrying, as it could lead to the emergence of untreatable invasive infections. All these factors reinforce the need for surveillance programs to monitor the evolution and dissemination of multidrug resistant and virulent strains among critically ill patients.

From the environment to the hospital: How plants can help to fight bacteria biofilm.

The emergence of resistance to antibiotics has become a global challenge as far as the control and treatment of nosocomial infections are concerned. Compared to the planktonic state, biofilms generally confer more resistance to antibiotics and may become a potential source of infection. Researchers are thus focused on developing novel drugs not as vulnerable as the current ones to bacterial resistance mechanisms and also able to target bacteria in biofilms. Natural products, especially those derived from plant sources, have substantiated significant medicinal activity with unique properties, making them perfect candidates for these much-needed therapeutics. Despite being a vast resource of antimicrobial molecules, limitations, including the low concentration of the extracted active compound and bioavailability, challenge the clinical application of medicinal plants to combat these infections. Nanotechnology through green synthesis is one of the strategies to explore the medicinal potential of plants. Research has established the promising outcome of this method in antibiofilm activity, in addition to improved drug delivery, targeting, and pharmacokinetic profiles. This review summarized the current knowledge on the potentialities of plant products as antibiotic adjuvants to restore the therapeutic activity of drugs. We also discussed biotechnological advances in medicinal plants to fight and eradicate biofilm-forming microorganisms.