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1.
Biomaterials ; 313: 122776, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39236629

RESUMO

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.


Assuntos
Células Dendríticas , Hidrogéis , Melanoma , Cicatrização , Hidrogéis/química , Animais , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Melanoma/terapia , Melanoma/patologia , Cicatrização/efeitos dos fármacos , Humanos , Recidiva Local de Neoplasia/prevenção & controle , Camundongos Endogâmicos C57BL , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos/farmacologia , Camundongos , Linhagem Celular Tumoral , Feminino
2.
JAMA Netw Open ; 7(9): e2432245, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39240563

RESUMO

Importance: Ambient air pollution and antimicrobial resistance pose significant global public health challenges. It is not known whether ambient air pollution is associated with increased consumption of antimicrobials. Objective: To assess whether a short-term association exists between ambient air pollution levels and antimicrobial consumption among the general population seeking primary care consultations for acute respiratory symptoms. Design, Setting, and Participants: This 2-stage cross-sectional ecological time series analysis study using data on daily ambient air pollution and antimicrobial consumption was conducted in the 11 largest cities in Catalonia, Spain, from June 23, 2012, to December 31, 2019, among all inhabitants aged 12 years or older. Statistical analysis was performed from November 2022 to December 2023. Exposures: Daily ambient air pollution (particulate matter of 10 µg/m3 [PM10], particulate matter of 2.5 µg/m3 [PM2.5], and nitrogen dioxide [NO2]). Main Outcomes and Measures: The main outcome was antimicrobial consumption associated with primary care consultations for acute respiratory symptoms in the 30 days before and after the dispensing of the antimicrobial. Antimicrobial consumption was measured as defined daily doses (DDDs) per 1000 inhabitants per day. Results: Among 1 938 333 inhabitants (median age, 48 years [IQR, 34-65 years]; 55% female participants), there were 8 421 404 antimicrobial dispensations, with a median of 12.26 DDDs per 1000 inhabitants per day (IQR, 6.03-15.32 DDDs per 1000 inhabitants per day). The median adjusted morbidity score was 2.0 (IQR, 1.0-5.0). For the 1 924 814 antimicrobial dispensations associated with primary care consultations for acute respiratory symptoms, there was a significant correlation between increases of 10 µg/m3 in the concentration of the 3 pollutants studied and heightened antimicrobial consumption at day 0 (PM10: relative risk [RR], 1.01 [95% CI, 1.01-1.02]; PM2.5: RR, 1.03 [95% CI, 1.01-1.04]; NO2: RR, 1.04 [95% CI, 1.03-1.05]). A delayed association emerged between increases in PM2.5 concentration and antimicrobial consumption between day 7 (RR, 1.00 [95% CI, 1.00-1.01]) and day 10 (RR, 1.00 [95% CI, 1.00-1.01]) after exposure. Conclusions and Relevance: In this 2-stage cross-sectional study using ecological time series analysis, short-term exposure to air pollution was associated with increased antimicrobial use associated with primary care consultations for acute respiratory symptoms in the general population. This finding could contribute to informing policy decisions aimed at reducing air pollution and its associated risks, thereby promoting respiratory health and reducing antimicrobial use.


Assuntos
Poluição do Ar , Humanos , Feminino , Masculino , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Pessoa de Meia-Idade , Estudos Transversais , Adulto , Espanha/epidemiologia , Idoso , Material Particulado/efeitos adversos , Material Particulado/análise , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos/efeitos adversos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Adolescente , Adulto Jovem , Criança , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia
3.
Parasite ; 31: 56, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39311470

RESUMO

Alveolar echinococcosis (AE) is a severe liver disease due to infection with the Echinococcus multilocularis larval stage, called the metacestode. Management of AE is based on benzimidazole chemotherapy (albendazole or mebendazole), associated with surgery when possible. Benzimidazoles are the only compounds recommended for the treatment of AE; however, these are parasitostatic, which means that the parasite can resume growth when treatment is interrupted. Also, benzimidazoles can cause liver dysfunction which may prevent their use. Numerous drugs have been reported to have in vitro activity against E. multilocularis, but few had satisfactory in vivo activity, and none were clearly more effective than benzimidazoles. These drugs belong to various therapeutic categories including anti-infective agents (e.g. amphotericin B, mefloquine, pentamidine derivatives), anti-neoplastic compounds (e.g. imatinib, nilotinib, bortezomib), plant-extracted compounds (e.g. thymol, crocin, carvacrol) and others (e.g. metformin, verapamil, thiaclopride). These treatments are generally of limited interest due to their toxicity, their unfavorable pharmacokinetics, or the scarcity of studies involving humans. Apart from benzimidazoles, only amphotericin B, mefloquine and nitazoxanide have been reported to be used for human AE treatment, with unsatisfactory results. Few studies have aimed at developing innovative strategies for AE drug therapy, such as vectorization of drugs using nanoparticles. Altogether, this review emphasizes the urgent need for new therapeutic strategies in AE management, for which there is currently no curative chemotherapy.


Title: Chimiothérapie de l'échinococcose alvéolaire : où en sommes-nous ? Abstract: L'échinococcose alvéolaire (EA) est une maladie sévère du foie due à l'infection par la forme larvaire d'Echinococcus multilocularis, appelée métacestode. La prise en charge de l'EA repose sur la chimiothérapie par benzimidazolés (albendazole ou mébendazole), si possible associée à la chirurgie. Les benzimidazolés sont les seules molécules recommandées dans le traitement de l'EA, toutefois, ceux-ci sont parasitostatiques, ce qui signifie que le parasite peut reprendre sa croissance lors d'une interruption du traitement. Également, les benzimidazolés peuvent causer une dysfonction hépatique qui peut empêcher leur utilisation. De nombreux médicaments ont été rapportés comme ayant une activité in vitro contre E. multilocularis, mais peu d'entre eux avaient une activité in vivo satisfaisante et aucun n'était clairement plus efficace que les benzimidazolés. Ces médicaments appartiennent à diverses catégories, notamment les agents anti-infectieux (par exemple l'amphotéricine B, la méfloquine, des dérivés de la pentamidine), les composés antinéoplasiques (par exemple l'imatinib, le nilotinib, le bortézomib), les composés extraits de plantes (par exemple le thymol, la crocine, le carvacrol) et d'autres (par exemple metformine, vérapamil, thiaclopride). Ces traitements présentent généralement un intérêt limité en raison de leur toxicité, de leur pharmacocinétique défavorable ou de la rareté des études menées chez l'homme. Outre les benzimidazolés, seules l'amphotéricine B, la méfloquine et la nitazoxanide ont été utilisées dans le traitement de l'EA humaine, avec des résultats insatisfaisants. Peu d'études se sont intéressées à développer des stratégies médicamenteuses innovantes contre l'EA, comme la vectorisation de médicaments à l'aide de nanoparticules. Cette revue souligne le besoin urgent de nouvelles stratégies thérapeutiques dans la prise en charge de l'EA, pour lesquelles il n'existe pas de chimiothérapie curative.


Assuntos
Equinococose , Echinococcus multilocularis , Humanos , Animais , Equinococose/tratamento farmacológico , Echinococcus multilocularis/efeitos dos fármacos , Anti-Helmínticos/uso terapêutico , Benzimidazóis/uso terapêutico , Equinococose Hepática/tratamento farmacológico , Albendazol/uso terapêutico , Antineoplásicos/uso terapêutico , Anti-Infecciosos/uso terapêutico
4.
PLoS One ; 19(9): e0310515, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39298455

RESUMO

Antimicrobials are frequently used in critically ill children admitted to the Paediatric Intensive Care Unit (PICU). The antimicrobial use data from Indian PICUs is limited using standard metrics such as Days of therapy (DOT). This study aimed to determine the baseline trend of antimicrobial use in PICU of a tertiary care teaching hospital of Raipur district of Chhattisgarh, India using standard metrics with the goal of developing facility-wide antibiotic policy and strengthening the antimicrobial stewardship activities. This active surveillance was conducted over a period of 18 months, from November 1, 2019, to March 21, 2021, in patients aged one month to 14 years who were admitted for ≥ 48 hours to the PICU at a tertiary care teaching hospital of Raipur District. Data on patient characteristics, antimicrobial indications, antimicrobial prescription information, and clinical outcomes were collected using pre-designed data abstraction forms. The descriptive statistic was used to represent the results. The antimicrobial consumption was analyzed according to the WHO AWaRe Class (Access, Watch, and Reserve groups) of antibiotics. The antimicrobial consumption was expressed as DOT/1000 patient-days (PD). A total of 216 patients were surveyed during the study period. The average number of antimicrobials prescribed per hospitalisation was 2.60 (range: 1-12), with 97.22% administered via parenteral route. Overall, DOT/1000-PD was 1318. The consumption of Watch Group antimicrobials was highest with 949 DOT/1000-PD, followed by Access (215) and Reserve Group (154), respectively. Ceftriaxone (208 DOT/1000 PD) was the most commonly prescribed antimicrobial agent, followed by Vancomycin (201), Meropenem (175), Piperacillin-Tazobactam (122) and Colistin (91). The patients who were escalated (28.24%) from empirical antimicrobial therapy had longer median PICU stay (8 days) compared those who were de-escalated (23.6%). Targeted therapy was given in 10.2% patients. The overall mortality rate was 14.35% and was higher (29.3%) in patients in whom empirical therapy was escalated compared to those who were de-escalated or continued. The study established a benchmark for antimicrobials use in the PICU and highlighted priority areas for antimicrobial stewardship intervention to enhance de-escalation rates, enhance targeted therapy, and reduce the overuse of antimicrobials especially belonging to the reserve group.


Assuntos
Antibacterianos , Gestão de Antimicrobianos , Unidades de Terapia Intensiva Pediátrica , Humanos , Criança , Índia , Pré-Escolar , Lactente , Feminino , Masculino , Adolescente , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Centros de Atenção Terciária
5.
Antimicrob Resist Infect Control ; 13(1): 101, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39256804

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) is a global public health concern that is fueled by the overuse of antimicrobial agents. Low- and middle-income countries, including those in Africa,. Point prevalence surveys (PPS) have been recognized as valuable tools for assessing antimicrobial utilization and guiding quality improvement initiatives. This systematic review and meta-analysis aimed to evaluate the prescription rates, indications, and quality of antimicrobial use in African health facilities. METHODS: A comprehensive search was conducted in multiple databases, including PubMed, Scopus, Embase, Hinari (Research4Life) and Google Scholar. Studies reporting the point prevalence of antimicrobial prescription or use in healthcare settings using validated PPS tools were included. The quality of the studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. A random-effects meta-analysis was conducted to combine the estimates. Heterogeneity was evaluated using Q statistics, I² statistics, meta-regression, and sensitivity analysis. Publication bias was assessed using a funnel plot and Egger's regression test, with a p-value of < 0.05 indicating the presence of bias. RESULTS: Out of 1790 potential studies identified, 32 articles were included in the meta-analysis. The pooled prescription rate in acute care hospitals was 60%, with significant heterogeneity (I2 = 99%, p < 0.001). Therapeutic prescriptions constituted 62% of all the prescribed antimicrobials. Prescription quality varied: documentation of reasons in notes was 64%, targeted therapy was 10%, and parenteral prescriptions were 65%, with guideline compliance at 48%. Hospital-acquired infections comprised 20% of all prescriptions. Subgroup analyses revealed regional disparities in antimicrobial prescription prevalence, with Western Africa showing a prevalence of 65% and 44% in Southern Africa. Publication bias adjustment estimated the prescription rate at 54.8%, with sensitivity analysis confirming minor variances among studies. CONCLUSION: This systematic review and meta-analysis provide valuable insights into antimicrobial utilization in African health facilities. The findings highlight the need for improved antimicrobial stewardship and infection control programs to address the high prevalence of irrational antimicrobial prescribing. The study emphasizes the importance of conducting regular surveillance through PPS to gather reliable data on antimicrobial usage, inform policy development, and monitor the effectiveness of interventions aimed at mitigating AMR.


Assuntos
Anti-Infecciosos , Humanos , África/epidemiologia , Anti-Infecciosos/uso terapêutico , Gestão de Antimicrobianos/normas , Gestão de Antimicrobianos/estatística & dados numéricos , Prescrições de Medicamentos/estatística & dados numéricos , Prescrições de Medicamentos/normas , Uso de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/normas , Prevalência
7.
Medicina (Kaunas) ; 60(9)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39336460

RESUMO

Background: The most problematic complication of external fixation is infection at the pin insertion site. Technology that improves the adhesion of the external fixation pin to the skin, subcutaneous tissue, and bone may prevent infection at the pin site. The purpose of this study is to formulate a calcium phosphate-fibroblast growth factor (Cp-FGF) coating on a stainless-steel external fixation pin and to verify its effectiveness in reducing infection at the pin site and its possible influence on bone fixation in animal experiments. Methods: We compared stainless-steel screws without coating (SS group; n = 32), those with a calcium phosphate coating (Cp group; n = 30), those with a Cp-FGF coating (FGF group; n = 32), and those with a Cp-FGF coating having enhanced biological activity (FGF+ group; n = 32) in male Japanese white domesticated rabbits. Screws were inserted percutaneously into the bilateral proximal tibial diaphysis of the rabbits and implanted for 4 weeks. Screws and periscrew tissue were observed postoperatively for qualitatively assessing infection. Results: Infection assessment by gross findings after 4 weeks (at screw removal) showed no significant differences between the groups. Histopathological evaluation of soft tissue infection and bone tissue infection showed no significant differences between the groups for either soft tissue or bone tissue. Since neither the FGF+ group nor the FGF group showed anti-infective effects, the biological activity of FGF is not the only determining factor. We compared SEM, XRD, coating detaching test, sustained release test, and bioassay to examine physicochemical properties among the coatings but found no sufficient differences. Conclusions: It is suggested that improving the tissue adhesion to and/or biocompatibility of pins is also important to improve the in vivo performance of Cp-FGF-coated external fixation pins.


Assuntos
Fatores de Crescimento de Fibroblastos , Aço Inoxidável , Animais , Coelhos , Masculino , Fatores de Crescimento de Fibroblastos/uso terapêutico , Fatores de Crescimento de Fibroblastos/administração & dosagem , Fatores de Crescimento de Fibroblastos/farmacologia , Pinos Ortopédicos , Materiais Revestidos Biocompatíveis , Fosfatos de Cálcio/uso terapêutico , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos/administração & dosagem
8.
J Int Med Res ; 52(9): 3000605241279236, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39308254

RESUMO

OBJECTIVE: To collect real-world data to demonstrate the safety and performance of Arrowg+ard Blue® /Arrowg+ard Blue Plus® (AGB/AGB+) central venous catheters (CVCs). METHODS: This observational, retrospective study involved patients who required AGB/AGB+ CVCs at designated general hospitals in USA (22), UK (19) and Germany (2). Data were extracted from electronic medical records. There were no specific inclusion/exclusion criteria. Primary endpoint was successful treatment without an adverse event (AE). Secondary endpoint was rate of AEs. RESULTS: In total, 384 cases were included from 43 centres and most patients (74%) were >35 years of age. A success rate of 99%, and an overall AE rate of 0.8% were observed. Moreover, the overall infection rate was lower than typically reported for standard catheters. In addition, power injection of contrast media was successful in all 51 cases. CONCLUSIONS: This study indicates the AGB/AGB+ CVCs perform as intended with a high success rate and few AEs. Further large-scale, controlled studies are required to confirm our findings.


Assuntos
Infecções Relacionadas a Cateter , Cateterismo Venoso Central , Cateteres Venosos Centrais , Humanos , Cateteres Venosos Centrais/efeitos adversos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Idoso , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/instrumentação , Cateterismo Venoso Central/métodos , Idoso de 80 Anos ou mais , Adolescente , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos/efeitos adversos
9.
BMC Public Health ; 24(1): 2632, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334050

RESUMO

Antimicrobial resistance has emerged as one of the foremost global public health challenges. While not a new issue, AMR has gained increasing attention due to the rise of multi-resistant pathogenic organisms, leading to higher mortality rates and significant economic burdens. To assess the knowledge, attitudes, and practices of the Bahir Dar City community regarding human and animal antimicrobial use and AMR, a community-based cross-sectional study was conducted from February to June 2023. The study area was selected purposively, and a simple random sampling approach was used to select kebeles, households, and individual participants. A total of 400 participants were enrolled in the study, with 63.25% being male and 31.25% having graduated from secondary school. Additionally, 61.5% of respondents were married, and the majority (46.5%) owned two species of animals. The findings revealed that 48.5% of the participants had moderate knowledge, 57.5% had positive attitudes, and 52.75% demonstrated good practices regarding antimicrobial resistance and usage. Chi-square analysis revealed statistically significant associations (p < 0.05) between respondents' knowledge level and their educational level, marital status, and position in the house. Attitude level were significantly associated (p < 0.05) with educational level, marital status, occupation, house ownership, and position in the house. Practice level also showed significant association (p < 0.05) with position in the house and occupation. Furthermore, there were significant associations among knowledge, attitude, and practice: knowledge was significantly associated with attitude (χ2 = 209.91, p ≤ 0.001), knowledge with practice (χ2 = 160.43, p ≤ 0.001), and attitude with practice (χ2 = 136.95, p ≤ 0.001). In conclusion, the study found a moderate level of knowledge, positive attitude, and good practice regarding antimicrobial usage and resistance among participants. It is recommended to promote responsible antimicrobial use across all sectors and encourage interdisciplinary collaboration.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Humanos , Etiópia , Masculino , Estudos Transversais , Feminino , Adulto , Animais , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Inquéritos e Questionários , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Farmacorresistência Bacteriana
12.
Rev Sci Tech ; 43: 168-176, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39222100

RESUMO

Misuse and overuse of antimicrobials in livestock production are identified as drivers for antimicrobial resistance (AMR). To improve decision-making concerning livestock health, it is important to understand the impact of AMR in livestock and aquaculture, within and beyond farm level, as well as expenditure on antimicrobial use (AMU). Such understanding provides grounds for systematic disease prioritisation and establishes a baseline for understanding the value of different strategies to mitigate animal health problems and for the monitoring and evaluation of the impact of those strategies. Yet limited data availability and quality surrounding AMU and AMR create barriers to furthering the knowledge of such impact. These data constraints are also more prevalent in contexts that lack the necessary resources to develop and maintain systematic and centralised data collection and collation systems. Even in regions with robust AMU and AMR monitoring systems in place, data limitations remain, such that the expenditure on antimicrobials and impacts of AMR remain unclear. Additionally, the current research funding strategies have been less focused on primary data collection, adding further barriers to filling the data void and reducing the global AMU/AMR knowledge gap. To work around the data scarcity and leverage previous and ongoing research efforts, it is vital to gain comprehensive knowledge of the people, projects and research consortia dedicated to the topic of AMU/AMR.


Les utilisations incorrecte et excessive d'agents antimicrobiens dans la production animale figurent parmi les facteurs connus de développement de résistances aux agents antimicrobiens (RAM). Pour améliorer la prise de décision relative à la santé des cheptels, il est essentiel de comprendre l'impact de la RAM chez les animaux d'élevage terrestres et aquatiques, aussi bien au niveau des élevages qu'au-delà, et de pouvoir quantifier les dépenses consacrées à l'utilisation d'agents antimicrobiens (UAM). Cette compréhension apporte les éléments d'information pour la priorisation systématique des maladies et établit un cadre de référence pour comprendre la valeur respective des différentes stratégies d'atténuation des problèmes de santé animale et pour assurer le suivi et l'évaluation d'impact de ces stratégies. Cependant, la disponibilité et la qualité limitées des données relatives à l'UAM et à la RAM font obstacle à une connaissance plus poussée de cet impact. Ces contraintes liées aux données sont plus répandues dans les contextes dépourvus des ressources nécessaires pour élaborer et entretenir des systèmes de collecte de données systématiques et centralisés. Même dans les régions où des systèmes robustes de suivi de l'UAM et de la RAM sont en place, le problème de l'insuffisance de données reste posé de sorte que la réalité des coûts induits par les agents antimicrobiens et l'impact de la RAM demeurent incertains. De plus, les stratégies actuelles de financement de la recherche ont été moins axées sur la collecte de données primaires, ce qui ajoute des obstacles supplémentaires pour l'obtention des données manquantes et compromet les efforts visant à réduire les écarts de connaissances sur l'UAM et la RAM à l'échelle mondiale. Afin de remédier à la pénurie de données et de mettre à profit les recherches antérieures et en cours, il est indispensable de savoir quels sont les acteurs, les projets et les consortiums de recherche qui travaillent sur l'UAM et la RAM.


El uso incorrecto y excesivo de antimicrobianos en la producción ganadera se considera un impulsor de la resistencia a los antimicrobianos (RAM). Para mejorar la toma de decisiones relativas a la sanidad del ganado, es importante comprender el impacto de la RAM en la ganadería y la acuicultura, a nivel de las granjas y más allá, así como el coste con el uso de antimicrobianos (UAM). Tal comprensión permite una priorización sistemática de enfermedades y establece una línea base para comprender el valor de las distintas estrategias destinadas a mitigar los problemas de sanidad animal, así como para supervisar y evaluar el impacto de esas estrategias. Sin embargo, la limitada disponibilidad y calidad de los datos en torno al UAM y a la RAM crean barreras que impiden ampliar la comprensión de dicho impacto. Estas limitaciones de datos también son más frecuentes en contextos que carecen de los recursos necesarios para desarrollar y mantener sistemas sistemáticos y centralizados de recopilación y cotejo de datos. Incluso en las regiones que cuentan con sistemas sólidos de seguimiento del UAM y la RAM, los datos siguen siendo limitados, de modo que los costes con antimicrobianos y las repercusiones de la resistencia a estos siguen sin estar claros. Además, las actuales estrategias de financiación de la investigación se han centrado menos en la recopilación de datos primarios, lo que añade más obstáculos a la hora de llenar el vacío de datos y reducir la brecha mundial de conocimientos sobre el UAM y la RAM. Para superar la escasez de datos y aprovechar las iniciativas de investigación previas y en curso, es fundamental adquirir un conocimiento detallado de las personas, los proyectos y los consorcios de investigación dedicados al tema del uso de antimicrobianos y la resistencia a estos.


Assuntos
Gado , Animais , Farmacorresistência Bacteriana , Criação de Animais Domésticos/métodos , Anti-Infecciosos/uso terapêutico , Antibacterianos
13.
Ulus Travma Acil Cerrahi Derg ; 30(9): 650-656, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39222499

RESUMO

BACKGROUND: Firearm injuries (FI) remain a significant cause of morbidity and mortality globally. Antibiotic use, supported by guideline recommendations for preventing post-injury infections in FI cases, encounters uncertainties regarding the selection of anti-microbial agents and associated outcomes. This study aimed to investigate the relationship between Injury Severity Scores (ISS) for FI cases presented to the emergency department. METHODS: We empirically revised antimicrobial treatment protocols based on culture results and mortality rates. In the study, 164 firearm injury cases, admitted to the emergency department in 2022 and subsequently hospitalized in clinics and intensive care units (ICU), were evaluated. Cases included in the study were categorized into four groups based on ISS: mild, moderate, severe, and profound injury severity. The study compared the timing of hospital presentation following the injury, hospital length of stay, tissue or blood culture positivity, empirical treatment administered, antimicrobial revision based on culture results, need for ICU admission, mortality status, and ISS among the cases. Data were analyzed using IBM SPSS Statistics 22.0 (SPSS Inc., Chicago, IL). Variables in trauma patients were compared among various groups using Pearson Chi-Square tests. Binary logistic regression tests were performed to identify independent risk factors. A significance level of p<0.05 was considered statistically significant. RESULTS: The study included 164 patients, all of whom were male. The mean age was calculated as 28.9±4.51 years. The average hospital length of stay was 25.54±21.81 days. Eighty-three patients (50.6%) required intensive care. Tissue cultures were obtained from 79 patients (48%). Bacterial growth was observed in 45 of these 79 patients (57%). The appropriate empirical antibiotic treatment rate, assessed among patients who received empirical treatment followed by culture-based antibiotic sensitivity testing, was 48.9%. It was observed that empirical antibiotic regimens were appropriate in 80% of cases in the mild group and 16.7% in the profound severe group (p=0.005). Our study compared the relationship between hospitalization duration and ISS groups. It was observed that hospitalization duration was significantly shorter in the mild group compared to the other groups (p=0.003, p=0.000, p=0.000). It was also observed that the need for ICU admission was higher in groups with higher ISS, indicating a correlation between higher ISS and increased ICU requirements (p=0.000). CONCLUSION: In conclusion, for cases of firearm injuries, we believe empirical antimicrobial therapy should be initiated with narrow-spectrum agents such as beta-lactam + beta-lactamase inhibitor or third-generation cephalosporin + nitroimidazole in the mild group, considering the lack of Pseudomonal activity.


Assuntos
Serviço Hospitalar de Emergência , Hospitalização , Ferimentos por Arma de Fogo , Humanos , Masculino , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Adulto , Hospitalização/estatística & dados numéricos , Pessoa de Meia-Idade , Escala de Gravidade do Ferimento , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Tempo de Internação/estatística & dados numéricos , Estudos Retrospectivos , Adulto Jovem , Anti-Infecciosos/uso terapêutico , Adolescente , Turquia/epidemiologia
14.
Int J Antimicrob Agents ; 64(4): 107306, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39146996

RESUMO

The HIV treatment landscape for adults has progressed dramatically in recent decades; however, paediatric populations continue to experience delayed and limited access to effective and safe antiretroviral therapy options. Despite current incentive programmes, formulation research and development and approved drug dosing for children have been limited, particularly for neonates (aged <4 wk). Regulatory approval of drug formulations and dosing in children may lag behind adult approvals by years. Formulation and trial design adjustments complicate paediatric drug development, all of which are vital to accommodate for physiological differences, organ maturation, and rapid weight gain, which are most significant in the youngest children. To facilitate more rapid anti-infective drug development for paediatric populations, regulatory agencies provide guidelines that include extrapolating efficacy and safety data from relevant populations; using pharmacokinetic (PK) bridging and modelling to reduce sample sizes and limit the number of PK studies needed before efficacy analyses; and enrolling age- or weight-based cohorts in parallel rather than sequentially for clinical trials. Ensuring access to approved drugs poses an additional challenge, as uncertainty in demand leads to manufacturing and supply complexity with potentially higher costs that can be a barrier to uptake. Here we summarise challenges in drug development for children living with HIV, which are not unique to antiretrovirals. We aim to propose strategies for how model-based approaches and global partnerships can overcome some of these barriers to accelerate paediatric drug development, with particular reference to HIV, and how lessons learnt from HIV could be extended to other anti-infectives.


Assuntos
Desenvolvimento de Medicamentos , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Criança , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacocinética , Ensaios Clínicos como Assunto , Pré-Escolar , Recém-Nascido , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos/farmacocinética , Antirretrovirais/uso terapêutico , Antirretrovirais/farmacocinética , Lactente
15.
Cell Rep Med ; 5(9): 101705, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39214083

RESUMO

Within the penile microbiome, bacteria associated with seroconversion, immunology, and cells (BASIC species) enhance HIV susceptibility in heterosexual uncircumcised men by inducing foreskin inflammation and HIV target cell recruitment. This phase 1/2 clinical trial randomizes HIV-uninfected Ugandan men (n = 125) to either oral tinidazole, topical metronidazole, topical clindamycin, or topical hydrogen peroxide to define impact on ex vivo foreskin HIV susceptibility, penile immunology, and BASIC species density. Antimicrobials are well tolerated, and 116 (93%) participants complete the protocol. Topical metronidazole and oral tinidazole reduce the inner foreskin tissue density of HIV-susceptible CD4+ T cells (predefined primary endpoint). Antimicrobials also have varying but substantial effects on reducing prepuce inflammation and BASIC species density, reducing density of foreskin T cell subsets, and increasing foreskin epithelial integrity. Immune alterations correlate strongly with changes in the abundance of BASIC species. Clinical interventions targeting the penile microbiota, particularly topical metronidazole, may reduce HIV susceptibility in uncircumcised men.


Assuntos
Infecções por HIV , Pênis , Humanos , Masculino , Infecções por HIV/imunologia , Infecções por HIV/tratamento farmacológico , Adulto , Pênis/imunologia , Pênis/microbiologia , Pênis/efeitos dos fármacos , Pênis/patologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Prepúcio do Pênis/imunologia , Suscetibilidade a Doenças , Circuncisão Masculina , Adulto Jovem , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Metronidazol/farmacologia , Metronidazol/administração & dosagem , Uganda
16.
Res Social Adm Pharm ; 20(11): 1023-1037, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39153871

RESUMO

OBJECTIVE: We sought to characterize and evaluate the effectiveness of pharmacist-led AMS interventions in improving antimicrobial use and subsequent surgical site infections (SSI) in perioperative settings. METHODS: A systematic review and meta-analysis was conducted by searching PubMed, Embase and CINAHL. Two independent reviewers extracted the data using the Descriptive Elements of Pharmacist Intervention Characterization Tool and undertook quality assessment using the Crowe Critical Appraisal. A meta-analysis was conducted using a random-effect model. RESULTS: Eleven studies were included in this review. Pharmacists were found to have various roles in AMS, including educational sessions, ward rounds, audits and feedback, and guidelines development. The discussion of interventions lacked details on the development. A meta-analysis revealed that pharmacist-led AMS programs in perioperative settings was associated with a significant improvement in antibiotic selection (OR 4.29; 95 % CI 2.52-7.30), administration time (OR 4.93; 95 % CI 2.05-11.84), duration (OR 5.27; 95 % CI 1.58-17.55), and SSI (OR 0.51; 95 % CI 0.34-0.77). CONCLUSION: Pharmacist-led AMS programs were effective in improving antimicrobial prescribing while reducing SSI; however most studies were of moderate quality. Studies lacked the utilization of theory to develop interventions, therefore, it is not clear whether theory-derived interventions are more effective than those without a theoretical element. High-quality, multicomponent, theory-derived, interventional studies using appropriate methodology and standardized data collection, are needed.


Assuntos
Gestão de Antimicrobianos , Farmacêuticos , Humanos , Farmacêuticos/organização & administração , Infecção da Ferida Cirúrgica/prevenção & controle , Assistência Perioperatória/métodos , Papel Profissional , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos/administração & dosagem
17.
Drug Discov Ther ; 18(4): 240-244, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39155084

RESUMO

Drug-resistant bacterial infections have become a substantial problem in various communities. Appropriate antimicrobial use is required because reducing antimicrobial use could reduce the number of resistant bacteria. The inappropriate use of antimicrobials can be prevented by improving the knowledge of patients, physicians, and other healthcare professionals; however, no antimicrobial awareness survey specifically aimed at patients has been conducted yet. Therefore, to promote proper antimicrobial use, mainly by patients, we conducted a survey on the attitudes of patients who brought their antimicrobial prescriptions from insurance pharmacies. The results were based on 858 responses. Awareness of the terms "bacteria, viruses, and antimicrobials" was > 80%, whereas that of "drug-resistant bacteria" was only 37.2%. Only 26.5% of respondents understood what the efficacy of antimicrobial drugs meant. Additionally, 31.5% of the respondents had experienced discontinuation antimicrobials, and approximately 70% of the reasons for discontinuation were self-judged symptom improvement. Furthermore, those who had experienced discontinuation were less aware of the various aspects of antimicrobial use than those who had not. In antimicrobial treatment, avoiding the emergence of drug-resistant bacteria is difficult, is detrimental to patients consuming treatment, and presents a major problem in society. Therefore, healthcare professionals should strive to optimize infectious disease treatment by providing appropriate guidance on the proper use of antimicrobials, significance of taking them, and harmful effects of their discontinuation to patients.


Assuntos
Farmacorresistência Bacteriana , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Inquéritos e Questionários , Idoso , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Adulto Jovem , Infecções Bacterianas/tratamento farmacológico , Adolescente
18.
Shock ; 62(4): 588-595, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39158545

RESUMO

ABSTRACT: Infection of wounds delays healing, increases treatment costs, and leads to major complications. Current methods to manage such infections include antibiotic ointments and antimicrobial wound dressings, both of which have significant drawbacks, including frequent reapplication and contribution to antimicrobial resistance. In this work, we developed wound dressings fabricated with a medical-grade polyurethane coating composed of natural plant secondary metabolites, cinnamaldehyde, and alpha-terpineol. Our wound dressings are easy to change and do not adhere to the wound bed. They kill gram-positive and -negative microbes in infected wounds due to the Food and Drug Administration-approved for human consumption components. The wound dressings were fabricated by dip coating. Antimicrobial efficacy was determined by quantifying the bacteria colonies after a 24 h of immersion. Wound healing and bacterial reduction were assessed in an in vivo full-thickness porcine burn model. Our antimicrobial wound dressings showed a > 5-log reduction (99.999%) of different gram-positive and gram-negative bacteria, while maintaining absorbency. In the in vivo porcine burn model, our wound dressings were superior to bacitracin in decreasing bacterial burden during daily changes, without interfering with wound healing. Additionally, the dressings had a significantly lower adhesion to the wound bed. Our antimicrobial wound dressings reduced the burden of clinically relevant bacteria more than commercial antimicrobial wound dressings. In an in vivo infected burn wound model, our coatings performed as well or better than bacitracin. We anticipate that our wound dressings would be useful for the treatment of various types of acute and chronic wounds.


Assuntos
Bandagens , Queimaduras , Cicatrização , Queimaduras/terapia , Queimaduras/microbiologia , Queimaduras/tratamento farmacológico , Animais , Suínos , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/terapia , Anti-Infecciosos/uso terapêutico , Bacitracina/uso terapêutico , Poliuretanos , Antibacterianos/uso terapêutico , Bactérias Gram-Positivas/efeitos dos fármacos , Acroleína/análogos & derivados , Acroleína/uso terapêutico , Acroleína/farmacologia
19.
Biomater Adv ; 164: 213990, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39154560

RESUMO

Microbial keratitis associated with contact lenses (CLs) wear remains a significant clinical concern. Antibiotic therapy is the current standard of care. However, the emergence of multidrug-resistant pathogens necessitates the investigation of alternative strategies. Antibiotic-free antimicrobial contact lenses (AFAMCLs) represent a promising approach in this regard. The effectiveness of CLs constructed with a variety of antibiotic-free antimicrobial strategies against microorganisms has been demonstrated. However, the impact of these antimicrobial strategies on CLs biocompatibility remains unclear. In the design and development of AFAMCLs, striking a balance between robust antimicrobial performance and optimal biocompatibility, including safety and wearing comfort, is a key issue. This review provides a comprehensive overview of recent advancements in AFAMCLs technology. The focus is on the antimicrobial efficacy and safety of various strategies employed in AFAMCLs construction. Furthermore, this review investigates the potential impact of these strategies on CLs parameters related to wearer comfort. This review aims to contribute to the continuous improvement of AFAMCLs and provide a reference for the trade-off between resistance to microorganisms and wearing comfort. In addition, it is hoped that this review can also provide a reference for the antimicrobial design of other medical devices.


Assuntos
Anti-Infecciosos , Humanos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Materiais Biocompatíveis/farmacologia , Lentes de Contato/microbiologia , Lentes de Contato/efeitos adversos , Ceratite/microbiologia , Ceratite/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
20.
Sci Rep ; 14(1): 17858, 2024 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090409

RESUMO

The standard treatment duration for acute cholangitis (AC) involves a 4-7-day antimicrobial treatment post-biliary drainage; however, recent studies have suggested that a ≤ 2-3 days is sufficient. However, clinical practice frequently depends on body temperature as a criterion for discontinuing antimicrobial treatment. Therefore, in this study, we assessed whether patients with AC can achieve successful outcomes with a ≤ 7-day antimicrobial treatment, even with a fever, assuming the infection source is effectively controlled. We conducted a single-center retrospective study involving patients with AC, defined following the Tokyo Guidelines 2018 for any cause, who underwent successful biliary drainage and completed a ≤ 7-day antimicrobial treatment. Patients were categorized into the febrile and afebrile groups based on their body temperature within 24 h before completing antimicrobial treatment. The primary outcome was the clinical cure rate, defined as no initial presenting symptoms by day 14 post-biliary drainage without recurrence or death by day 30. The secondary outcome was a 3-month recurrence rate. Logistic regression with inverse probability of treatment weighting was used. Overall, 408 patients were selected, among whom 40 (9.8%) were febrile. The two groups showed no significant differences in the clinical cure and 3-month recurrence rates. Notably, the subgroups limited to patients with a ≤ 3-day antibiotic treatment duration also showed no differences in these outcomes. Therefore, our results suggest that discontinuing antibiotics within the initially planned treatment period was sufficient for successful drainage cases of AC, regardless of the patient's fever status during the 24 h leading up to termination.


Assuntos
Colangite , Drenagem , Febre , Humanos , Colangite/tratamento farmacológico , Masculino , Feminino , Febre/tratamento farmacológico , Febre/etiologia , Idoso , Estudos Retrospectivos , Doença Aguda , Pessoa de Meia-Idade , Resultado do Tratamento , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Idoso de 80 Anos ou mais , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos/administração & dosagem , Recidiva
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