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With the increasing rate of infections caused by multidrug-resistant organisms (MDRO), selecting appropriate empiric antibiotics has become challenging. We aimed to develop and externally validate a model for predicting the risk of MDRO infections in patients with cirrhosis. METHODS: We included patients with cirrhosis and bacterial infections from two prospective studies: a transcontinental study was used for model development and internal validation (n = 1302), and a study from Argentina and Uruguay was used for external validation (n = 472). All predictors were measured at the time of infection. Both culture-positive and culture-negative infections were included. The model was developed using logistic regression with backward stepwise predictor selection. We externally validated the optimism-adjusted model using calibration and discrimination statistics and evaluated its clinical utility. RESULTS: The prevalence of MDRO infections was 19% and 22% in the development and external validation datasets, respectively. The model's predictors were sex, prior antibiotic use, type and site of infection, MELD-Na, use of vasopressors, acute-on-chronic liver failure, and interaction terms. Upon external validation, the calibration slope was 77 (95% CI .48-1.05), and the area under the ROC curve was .68 (95% CI .61-.73). The application of the model significantly changed the post-test probability of having an MDRO infection, identifying patients with nosocomial infection at very low risk (8%) and patients with community-acquired infections at significant risk (36%). CONCLUSION: This model achieved adequate performance and could be used to improve the selection of empiric antibiotics, aligning with other antibiotic stewardship program strategies.

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AIM: Natural bioactive products have been tested as alternative antimicrobial agents. This study evaluated the effect of Punica granatum extract (PGE) on oral multispecies biofilms. METHODOLOGY: Lyophilized extracts from pomegranate peel were prepared, and the punicalagin content was assessed by ultra-performance liquid chromatography (UPLC). Oral multispecies biofilms from 2 donors were grown on four collagen-coated hydroxyapatite discs. After incubation for 7 days or 3 weeks, the biofilms were exposed to water (control), 2% CHX, 10% PGE, 20% PGE or 30% PGE for 3 min. The proportions of dead bacteria were assessed by the live/dead staining and confocal microscopy. After the analysis, the best PGE concentration (30%) was combined with CHX. The experimental phases were repeated using water, 2% CHX, 30% PGE and 30% PGE + 2% CHX. Five random areas of the biofilm on each disc were scanned, resulting in 20 scanned areas for each group. RESULTS: Regarding the biofilm volume, no differences were found amongst solutions (p = .111). The PGE solution killed bacteria effectively in 1-week, 2-week and 3-week-old-plaque biofilms, ranging from 37 to 55.3%, depending on the PGE concentration. The 30% PGE (a) (p = .0009) had greater antibiofilm effectiveness than 2% CHX (b), which killed bacteria in the 25.2 to 48.7% range. The 10% and 20% PGE had intermediate values (ab), without significant differences from 30% PGE (p = 1.002). Water (c) had the lowest proportion of dead bacteria (p < .00001) in a range of 5 to 6.7% and lower effectiveness in killing bacteria (p < .05). The PGE alone or mixed with 2% CHX had greater anti-biofilm effectiveness than CHX (p < .05). The old plaque biofilms were more resistant than the 7-day-old plaque (p < .05). CONCLUSIONS: The 30% PGE (alone or combined with CHX) exhibited a greater antibiofilm effect on oral multispecies biofilms grown on hydroxyapatite discs than 2% CHX.

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Open fractures are highly incident injuries closely related to the modern life, in which accidents caused by motor vehicles or other machines impart high energy to bone tissue. Individual morbidity is represented by the functional impairment resultant of infection, nonunion, or vicious healing. In terms of public health, there are huge costs involved with the treatment of these fractures, particularly with their complications. One of the critical issues in managing open fractures is the use of antibiotics (ATB), including decisions about which specific agents to administer, duration of use, and ideal timing of the first prophylactic dose. Although recent guidelines have recommended starting antibiotic prophylaxis as soon as possible, such a recommendation appears to stem from insufficient evidence. In light of this, we conducted a systematic review, including studies that addressed the impact of the time to first antibiotic and the risk of infectious outcomes. Fourteen studies were selected, of which only four found that the early initiation of treatment with antibiotics is able to prevent infection. All studies had important risks of bias. The results indicate that this question remains open, and further prospective and methodologically sound studies are necessary in order to guide practices and health policies related to this matter. Level of Evidence II; Therapeutic Studies Investigating the Results Level of Treatment.

As fraturas expostas são lesões altamente incidentes, intimamente relacionadas à vida moderna, na qual os acidentes causados por veículos automotores ou outros aparatos transmitem alta energia ao tecido ósseo. A morbidade individual é representada pelo comprometimento funcional resultante de infecção, não-união ou cicatrização viciosa. Há enormes custos envolvidos no tratamento dessas fraturas em termos de saúde pública, principalmente quanto as complicações. Uma das questões críticas no tratamento de fraturas expostas é o uso de antibióticos, incluindo as decisões sobre quais agentes específicos devem ser administrados, a duração e o momento ideal para a primeira dose profilática. Embora as diretrizes recentes tenham recomendado o início da profilaxia antibiótica o mais rápido possível, essa recomendação parece se basear em evidências insuficientes. Em vista disso, realizamos uma revisão sistemática, incluindo estudos que abordaram o impacto do tempo até o primeiro antibiótico e o risco de resultados infecciosos. Foram selecionados 14 estudos, dos quais apenas quatro concluíram que o início precoce do tratamento com antibióticos é capaz de prevenir infecções. Todos os estudos tinham riscos importantes de viés. Os resultados indicam que essa questão permanece em aberto, sendo necessários mais estudos prospectivos e metodologicamente sólidos para orientar as práticas e políticas de saúde relacionadas a esse assunto. Nível de Evidência II; Estudos Terapêuticos que Investigam o Nível de Resultados do Tratamento.

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Objective: Acne is a chronic inflammatory disease that involves the pilosebaceous follicle. Its pharmacological treatment involves topical and systemic medications, but a heterogeneous group of drugs may exacerbate or induce skin lesions. The aim of this study was to identify the pharmacological management and medications related to the exacerbation of skin lesions in patients diagnosed with acne. Methods: This was a cross-sectional study that identified the outpatient medication prescription patterns of patients with acne from a dispensing database of 8.5 million members of the Colombian Health System. Sociodemographic and pharmacological variables and the identification of prescriptions that were potentially inappropriate due to the risk of worsening acne were considered. Results: A total of 21,604 patients with acne were identified. Median age was 20.8 years (interquartile range: 17.3-27.3 years), and 60.7 percent were female. Treatment mainly involved antibiotics (79.9% of patients), especially doxycycline (66.0%), and retinoids (55.7%). A total of 17.2 percent of patients had potentially inappropriate prescriptions, predominantly progestogens with androgenic properties (8.9%). Female patients (odds ratio [OR]: 3.55; 95% confidence interval [CI]:3.24-3.90) and patients with pathologies such as systemic lupus erythematosus (OR: 18.61; 95% CI: 7.23-47.93) and rheumatoid arthritis (OR: 10.80; 95% CI: 5.02-23.23) were more likely to receive inappropriate prescriptions, and the risk increased with each year of life (OR: 1.02; 95% CI: 1.02-1.03). Limitations: Access to medical records was not obtained to verify clinical characteristics of acne. Conclusion: Patients with acne are excessively treated with systemic antibiotics, counter to clinical practice guidelines. Approximately one-fifth of these patients received some potentially inappropriate medication that could exacerbate their skin lesions.

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Background: The scope of the study was to analyze original preclinical studies on the antimicrobial effects of carvacrol and derivatives on the Mycobacterium genus. Materials & methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, four databases (PubMed, Web of Science, SCOPUS and EMBASE) were searched. Results: The search retrieved 392 records, of which 11 papers were selected. Heterogeneity in the techniques and mycobacterial targets was observed. Carvacrol demonstrated synergistic antimycobacterial activity with rifampicin against multidrug-resistant Mycobacterium tuberculosis on membranes and biofilms. In silico approaches showed specific targets in mycobacteria, by inhibition and molecular docking assays, on the enzyme chorismate mutase and the heat shock protein 16.3. Conclusion: Carvacrol has been shown to be a scaffold candidate for future molecules with activity against mycobacteria.

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Burkholderia cepacia complex (Bcc) is a bacterial group with 'natural' multi-antimicrobial resistance. This complex has generated epidemic outbreaks across the world. In people with cystic fibrosis (CF), Bcc can cause severe lung infections that lead to accelerated lung damage, which can be complicated by necrotizing pneumonia accompanied by high fevers, leucocytosis, and bacteraemia, which commonly causes fatal outcomes. Specifically, infection by Burkholderia cenocepacia is considered an exclusion criterion for lung transplantation. The species of Bcc exhibit both genetic and phenotypic hypervariability that complicate their accurate microbiological identification. Automated methods such as MALDI-TOF can err in the determination of species. Their slow growth even in selective agars and the absence of international consensuses on the optimal conditions for their isolation make early diagnosis a difficult challenge to overcome. The absence of correlations between antibiograms and clinical results has resulted in the absence of standardized cut-off values of antimicrobial susceptibility, a fact that brings a latent risk since incorrect antibiotic therapy can induce the selection of more aggressive variants that worsen the clinical picture of the host, added to the absence of a clear therapeutic guide for the eradication of pulmonary infections by Bcc in patients with CF, resulting in frequently ineffective treatments. There is an urgent need to standardize methods and diagnostic tools that would allow an early and accurate diagnosis, as well as to perform clinical studies of the effectiveness of available antibiotics to eradicate Bcc infections, which would allow us to establish standardized therapeutic schemes for Bcc-infected patients.

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Zinc oxide nanoparticles were synthesized from the leaf extract of Brassica oleracea L. Acephala group (collard green) followed by their characterization using Scanning Electron Microscope (SEM), and Energy Dispersive X-ray (EDX). The antibacterial properties of zinc nanoparticles were tested against Gram-negative bacteria, Pseudomonas aeruginosa (ATCC ® 9027™), Escherichia coli (ATCC ® 8739™), Klebsiella pneumoniae (ATCC® BAA-1705™) and Gram-positive bacteria, Staphylococcus aureus (ATCC ® 6538™) and Listeria monocytogenes (ATCC ® 13932™), at four different concentrations (50.00 µg/ml, 100.00 µg/ml, 500.00 µg/ml and 1 mg/ml) of zinc oxide nanoparticles suspension. Results revealed that the synthesized nanoparticles exhibit strong antibacterial effects against Pseudomonas aeruginosa, Listeria monocytogenes, Klebsiella pneumonia, Staphylococcus aureus and Escherichia coli at 500.00 µg/ml-1 mg/ml concentrations. An increase in efficacy of nanoparticles with the decrease of their size was also evident. This is a first ever report on Brassica oleracea, L. based nanoparticles which demonstrates that 500.00 µg-1 mg/ml conc. of zinc oxide nanoparticles have antibacterial activity against both Gram -ve and Gram +ve bacteria and have the potential to be considered as an antibacterial agent in future.

Nanopartículas de óxido de zinco foram sintetizadas a partir do extrato foliar de Brassica oleracea L., grupo Acephala (couve), seguidas de sua caracterização em Microscópio Eletrônico de Varredura (MEV) e Raio X por Energia Dispersiva (EDX). As propriedades antibacterianas das nanopartículas de zinco foram testadas em bactérias Gram-negativas, Pseudomonas aeruginosa (ATCC® 9027™), Escherichia coli (ATCC® 8739™) e Klebsiella pneumoniae (ATCC® BAA-1705™), e bactérias Gram-positivas, Staphylococcus aureus (ATCC® 6538™) e Listeria monocytogenes (ATCC® 13932™), em quatro concentrações diferentes (50,00 µg / ml; 100,00 µg / ml; 500,00 µg / ml; e 1 mg / ml) de suspensão de nanopartículas de óxido de zinco. Os resultados revelaram que as nanopartículas sintetizadas exibem fortes efeitos antibacterianos contra P. aeruginosa, L. monocytogenes, K. pneumonia, S. aureus e E. coli em concentrações de 500,00 µg / ml-1 mg / ml. Um aumento na eficácia das nanopartículas com a diminuição de seu tamanho também foi evidente. Este é o primeiro relatório sobre nanopartículas à base de B. oleracea L. que demonstra que 500,00 µg-1 mg / ml de concentração de nanopartículas de óxido de zinco têm atividade antibacteriana contra bactérias Gram-negativas e Gram-positivas e que essas nanopartículas têm potencial para ser consideradas um agente antibacteriano no futuro.

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The presence of pathogenic bacteria in food is considered as a primary cause of food-borne illness and food quality deterioration worldwide. The present study aimed to determine the effectiveness of five essential oils (EOs) against multidrug-resistant foodborne pathogens. In the current study Gram-negative bacteria (Escherichia, Enterobacter, Citrobacter, Proteus, Pseudomonas, and Klebsiella) and the Gram-positive bacteria Staphylococcus were isolated from raw milk and biochemically characterized. The anti-bacterial effect of different antibiotics and EOs (thyme, oregano, lemongrass, mint, and rosemary) was determined using the standard disc diffusion method. The antibiogram study revealed that Gram-negative bacteria were highly resistant to penicillin while Staphylococcus was resistant to streptomycin, amoxicillin, and lincomycin. Moderate resistance was observed to doxycycline, amikacin, enrofloxacin, kanamycin and cefixime. Isolates were found less resistant to gentamycin, chloramphenicol, and ciprofloxacin. EOs showed a broad range of antimicrobial activity against all bacteria except P. aeruginosa. Of these, thyme was more effective against most of the multi-drug resistant bacterial strains and formed the largest zone of inhibition (26 mm) against Escherichia followed by oregano oil (18 mm) against Staphylococcus (p<0.05). Klebsiella spp and Citrobacter spp showed resistance to mint and lemongrass oil respectively. The EOs such as lemongrass, mint and rosemary were less active against all the bacteria. The findings of the recent study suggest the use of EOs as natural antibacterial agents for food preservation.

A presença de bactérias patogênicas em alimentos é considerada a principal causa de doenças transmitidas por alimentos e deterioração da qualidade dos alimentos em todo o mundo. O presente estudo teve como objetivo determinar a eficácia de cinco óleos essenciais (OEs) contra patógenos de origem alimentar multirresistentes. No presente estudo, bactérias Gram-negativas (Escherichia, Enterobacter, Citrobacter, Proteus, Pseudomonas e Klebsiella) e as bactérias Gram-positivas Staphylococcus foram isoladas do leite cru e caracterizadas bioquimicamente. O efeito antibacteriano de diferentes antibióticos e OEs (tomilho, orégano, capim-limão, hortelã e alecrim) foi determinado usando o método padrão de difusão em disco. O estudo do antibiograma revelou que as bactérias Gram-negativas eram altamente resistentes à penicilina, enquanto o Staphylococcus era resistente à estreptomicina, amoxicilina e lincomicina. Foi observada resistência moderada à doxiciclina, amicacina, enrofloxacina, canamicina e cefixima. Os isolados foram encontrados menos resistentes à gentamicina, cloranfenicol e ciprofloxacina. Os OEs mostraram uma ampla gama de atividade antimicrobiana contra todas as bactérias, exceto P. aeruginosa. Destes, o tomilho foi mais eficaz contra a maioria das cepas bacterianas multirresistentes e formou a maior zona de inibição (26 mm) contra Escherichia seguido de óleo de orégano (18 mm) contra Staphylococcus (p<0,05). Klebsiella spp e Citrobacter spp apresentaram resistência ao óleo de menta e capim-limão, respectivamente. Os OEs como capim-limão, hortelã e alecrim foram menos ativos contra todas as bactérias. Os resultados do estudo recente sugerem o uso de OEs como agentes antibacterianos naturais para conservação de alimentos.

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The present study was conducted to isolate and characterize bacteria from water and soil sample taken from the Lahore Canal at different sites i.e. Mall Road, Mohlanwal and Khera site. Isolated bacterial strains were identified on the basis of morphological and biochemical tests. Identification was confirmed by culturing bacteria on selective media. Antibiotic resistance test was also performed to observe the resistance of bacteria against different antibiotics. Blood agar test was performed for identification of different pathogenic bacteria. The result revealed that water and soil samples of Lahore Canal Lahore from different sites were contaminated with Escherichia coli, Salmonella sp., Vibrio sp., Bacillus spp., Enterococcus sp. and Staphylococcus spp. Due to presence of these pathogens, this water is not suitable for any domestic and irrigation use. Study also revealed that water of the Lahore Canal is harmful for human health as it is contaminated with bacteria that can cause severe disease e.g., Escherichia coli can cause gastroenteritis, Bacillus spp. can cause nausea and vomiting, Enterococcus may infect urinary tract, Salmonella sp. is responsible for Bacteremia, Staphylococcus spp. can cause mild fever and Vibrio sp. can be the reason of cholera. Thus it is rendered unfit for any kind of human use even other than drinking like swimming, bathing, washing etc., until and unless some remedial measures are employed to eradicate pathogenic microorganisms by WASA and LWMS according to standards of WHO. Similarly, it is quite harmful, when and where ever it is used for irrigation without proper treatment.

O presente estudo foi realizado para isolar e caracterizar bactérias de amostras de água e solo retiradas do Canal Lahore, em Lahore, em diferentes locais, ou seja, Mall Road, Mohlanwal e Khera. As cepas bacterianas isoladas foram identificadas com base em testes morfológicos e bioquímicos. A identificação foi confirmada por cultura de bactérias em testes de meios seletivos. O teste de resistência aos antibióticos também foi realizado para observar a resistência das bactérias a diferentes antibióticos. Foi realizado o teste de ágar sangue para identificar diferentes bactérias patogênicas. O resultado revelou que amostras de água e solo do Canal Lahore, Lahore, de diferentes localidades estavam contaminadas com Escherichia coli, Salmonella sp., Vibrio sp., Bacillus spp., Enterococcus sp. e Staphylococcus spp. Por causa da presença desses patógenos, essa água não é adequada para qualquer uso doméstico e de irrigação. O estudo revelou que a água do Canal Lahore é prejudicial à saúde humana, pois está contaminada com bactérias que podem causar doenças graves, por exemplo: Escherichia coli pode ocasionar gastroenterite; Bacillus spp. pode causar náuseas e vômitos; Enterococcus sp. pode infectar o trato urinário; Salmonella sp. é responsável pela bacteremia; Staphylococcus spp. pode causar febre leve; e Vibrio sp. pode ser a razão da cólera. Assim, torna-se imprópria para uso humano, como natação, banho, lavagem etc., até que algumas medidas corretivas sejam empregadas para erradicar microrganismos patogênicos por WASA e LWMS de acordo com os padrões da OMS. Da mesma forma, é bastante prejudicial, quando usada para irrigação sem tratamento adequado.

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ABSTRACT Open fractures are highly incident injuries closely related to the modern life, in which accidents caused by motor vehicles or other machines impart high energy to bone tissue. Individual morbidity is represented by the functional impairment resultant of infection, nonunion, or vicious healing. In terms of public health, there are huge costs involved with the treatment of these fractures, particularly with their complications. One of the critical issues in managing open fractures is the use of antibiotics (ATB), including decisions about which specific agents to administer, duration of use, and ideal timing of the first prophylactic dose. Although recent guidelines have recommended starting antibiotic prophylaxis as soon as possible, such a recommendation appears to stem from insufficient evidence. In light of this, we conducted a systematic review, including studies that addressed the impact of the time to first antibiotic and the risk of infectious outcomes. Fourteen studies were selected, of which only four found that the early initiation of treatment with antibiotics is able to prevent infection. All studies had important risks of bias. The results indicate that this question remains open, and further prospective and methodologically sound studies are necessary in order to guide practices and health policies related to this matter. Level of Evidence II; Therapeutic Studies Investigating the Results Level of Treatment.

RESUMO As fraturas expostas são lesões altamente incidentes, intimamente relacionadas à vida moderna, na qual os acidentes causados por veículos automotores ou outros aparatos transmitem alta energia ao tecido ósseo. A morbidade individual é representada pelo comprometimento funcional resultante de infecção, não-união ou cicatrização viciosa. Há enormes custos envolvidos no tratamento dessas fraturas em termos de saúde pública, principalmente quanto as complicações. Uma das questões críticas no tratamento de fraturas expostas é o uso de antibióticos, incluindo as decisões sobre quais agentes específicos devem ser administrados, a duração e o momento ideal para a primeira dose profilática. Embora as diretrizes recentes tenham recomendado o início da profilaxia antibiótica o mais rápido possível, essa recomendação parece se basear em evidências insuficientes. Em vista disso, realizamos uma revisão sistemática, incluindo estudos que abordaram o impacto do tempo até o primeiro antibiótico e o risco de resultados infecciosos. Foram selecionados 14 estudos, dos quais apenas quatro concluíram que o início precoce do tratamento com antibióticos é capaz de prevenir infecções. Todos os estudos tinham riscos importantes de viés. Os resultados indicam que essa questão permanece em aberto, sendo necessários mais estudos prospectivos e metodologicamente sólidos para orientar as práticas e políticas de saúde relacionadas a esse assunto. Nível de Evidência II; Estudos Terapêuticos que Investigam o Nível de Resultados do Tratamento.

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Abstract Background: Pneumonia occurs in about 20% of trauma patients with pulmonary contusions. This study aims to evaluate the association between empirical antibiotic therapy and nosocomial pneumonia in this population. Methods: Retrospective cohort of adult patients admitted to a trauma-surgical ICU. The Antibiotic Therapy Group (ATG) was defined by intravenous antibiotic use for more than 48 h starting on hospital admission, while the Conservative Group (CG) was determined by antibiotic use no longer than 48 h. Primary outcome was microbiologically documented nosocomial pneumonia within 14 days after hospital admission. Logistic regression was used to estimate the association between group allocation and primary outcome. Exploratory analyses evaluating the association between resistant strains in pneumonia and antibiotic use were performed. Results: The study included 177 patients with chest trauma and pulmonary contusion on CTscan. ATG were more severely ill than CG, as shown by higher Injury Severity Score, SAPS3, SOFA score, higher rates, and longer duration of mechanical ventilation. In the multivariate analysis, ATG was associated with a lower incidence of primary outcome (OR = 0.25, 95% CI 0.09-0.64; p < 0.01). Similar results were found in the sensitivity analysis with another set of variables. However, each day of antibiotic use was associated with an increased risk of pneumonia by resistant bacteria (OR = 1.18 per day, 95% CI 1.05-1.36; p < 0.01). Conclusions: Empiric antibiotic therapy was independently associated with lower incidence of nosocomial pneumonia in critically ill patients with pulmonary contusion. However, each day of antibiotic use was associated with increased resistant strains in infected patients.

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Introduction: Millions of snake bites occur worldwide each year. Clinical practice guidelines generally do not recommend the use of prophylactic antibiotics. Objective: To determine the sociodemographic, clinical, and pharmacological variables and the use of antibiotics in a group of patients with snake bites in Colombia. Methods: A retrospective cross-sectional study was carried out. Patients affiliated with a Colombian health insurer who presented with snake bites between 2015 and 2022 were included. The cases were identified from the National Public Health Surveillance System. Sociodemographic, clinical and pharmacological variables were identified. Descriptive and bivariate analyses were performed. Results: A total of 643 patients were analyzed, with a median age of 30.8 years, and 74.7% were men. The most frequently identified genus of snake was Bothrops (88.8%), and most incidents were classified as mild ophidian accidents (61.6%). A total of 59.7% of patients received snake antivenom. A total of 13.8% and 2.2% of the patients had cellulitis or abscesses, respectively. A total of 63.5% received antibiotics (50.6% for prophylaxis and 12.9% for treatment), especially cephalexin (25.9%), and most of the antibiotic management was considered inappropriate (91.7%). Conclusion: Most patients with snake bites received antibiotics, especially for prophylactic purposes, a clinical behavior that goes against current evidence. The use of antibiotics with an unsuitable spectrum for the microorganisms that are usually found in the wounds of these patients is frequent. The development of local clinical practice guidelines is required to help reduce the overprescription of antibiotics, as the excessive use of antimicrobials is the main determinant of antimicrobial resistance.

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Aim: The study aimed to review experimental models using cyclodextrins to improve antibacterial drugs' physicochemical characteristics and biological activities. Methods: The following terms and their combinations were used: cyclodextrins and antibacterial agents in title or abstract, and the total study search was conducted over a period up to October 2022. The review was carried out using PubMed, Scopus and Embase databases. A total of 1580 studies were identified, of which 27 articles were selected for discussion in this review. Results: The biological results revealed that the antibacterial effect of the inclusion complexes was extensively improved. Cyclodextrins can enhance the therapeutic effects of antibiotics already existing on the market, natural products and synthetic molecules. Conclusion: Overall, CDs as drug-delivery vehicles have been shown to improve antibiotics solubility, stability, and bioavailability, leading to enhanced antibacterial activity.

The overuse of drugs can cause bacteria to become less susceptible to them. This is known as resistance. One idea on how to tackle this resistance is by using cyclodextrins (CDs). CDs can change how drugs work, making them better at fighting bacteria. As CDs are already used in making drugs, they are a good choice for the basis of creating new drugs.

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According to the WHO, antimicrobial resistance is among the top 10 threats to global health. Due to increased resistance rates, an increase in the mortality and morbidity of patients has been observed, with projections of more than 10 million deaths associated with infections caused by antibacterial resistant microorganisms. Our research group has developed a new family of pyrimido-isoquinolin-quinones showing antibacterial activities against multidrug-resistant Staphylococcus aureus. We have developed 3D-QSAR CoMFA and CoMSIA studies (r2 = 0.938; 0.895), from which 13 new derivatives were designed and synthesized. The compounds were tested in antibacterial assays against methicillin-resistant Staphylococcus aureus and other bacterial pathogens. There were 12 synthesized compounds active against Gram-positive pathogens in concentrations ranging from 2 to 32 µg/mL. The antibacterial activity of the derivatives is explained by the steric, electronic, and hydrogen-bond acceptor properties of the compounds.

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In this work, we report a two-step methodology for the synthesis of small silver nanoparticles embedded into hydrogels based on chitosan (CS) and hydroxypropyl methylcellulose (HPMC) biopolymers. This method uses d-glucose as an external green reducing agent and purified water as a solvent, leading to an eco-friendly, cost-effective, and biocompatible process for the synthesis of silver nanocomposite hydrogels. Their characterization comprises ultraviolet-visible spectroscopy, Fourier-transform infrared spectra, differential scanning calorimetry, scanning electron microscopy with energy-dispersive spectroscopy, and transmission electron microscopy assays. Moreover, the structural stability of the hydrogels was investigated through sequential swelling-deswelling cycles. The nanomaterials showed good mechanical properties in terms of their structural stability and revealed prominent antibacterial properties due to the reduced-size particles that promote their use as new advanced antimicrobial agents, an advantage compared to conventional particles in aqueous suspension that lose stability and effectiveness. Finally, theoretical analyses provided insights into the possible interactions, charge transfer, and stabilization process of nanoclusters mediated by the high-electron-density groups belonging to CS and HPMC, revealing their unique structural properties in the preparation of nano-scaled materials.

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BACKGROUND: Pneumonia occurs in about 20% of trauma patients with pulmonary contusions. This study aims to evaluate the association between empirical antibiotic therapy and nosocomial pneumonia in this population. METHODS: Retrospective cohort of adult patients admitted to a trauma-surgical ICU. The Antibiotic Therapy Group (ATG) was defined by intravenous antibiotic use for more than 48 h starting on hospital admission, while the Conservative Group (CG) was determined by antibiotic use no longer than 48 h. Primary outcome was microbiologically documented nosocomial pneumonia within 14 days after hospital admission. Logistic regression was used to estimate the association between group allocation and primary outcome. Exploratory analyses evaluating the association between resistant strains in pneumonia and antibiotic use were performed. RESULTS: The study included 177 patients with chest trauma and pulmonary contusion on CT scan. ATG were more severely ill than CG, as shown by higher Injury Severity Score, SAPS3, SOFA score, higher rates, and longer duration of mechanical ventilation. In the multivariate analysis, ATG was associated with a lower incidence of primary outcome (OR = 0.25, 95% CI 0.09-0.64; p < 0.01). Similar results were found in the sensitivity analysis with another set of variables. However, each day of antibiotic use was associated with an increased risk of pneumonia by resistant bacteria (OR = 1.18 per day, 95% CI 1.05-1.36; p < 0.01). CONCLUSIONS: Empiric antibiotic therapy was independently associated with lower incidence of nosocomial pneumonia in critically ill patients with pulmonary contusion. However, each day of antibiotic use was associated with increased resistant strains in infected patients.

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Aim: To evaluate the effect of a new Fe-cyclam complex on pathogenic bacterial species, including multidrug-resistant clinical specimens. Materials & methods: The complex [Fe(cyclam)ox]PF6 (D2) was tested in cytotoxicity and MIC tests. Clinical and reference strains of Gram-negative and Gram-positive bacteria were used. Considering Staphylococcus aureus strains, the profile of antimicrobial susceptibility and time-kill kinetics for D2 was performed. An in silico analysis for D2 was also performed. Results: D2 showed broad bacterial activity, mainly against specimens of Cutibacterium acnes, S. aureus, Pseudomonas aeruginosa and Acinetobacter baumannii. Low cytotoxicity in human cells was demonstrated. Conclusion: The tested compound proved to be a promising agent against resistant bacterial infections.

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INTRODUCTION: Inadequate prescription of antibiotics has been recognized as a public health problem by the World Health Organization. In this context, antibiotic stewardship programs have been implemented as a tool to mitigate its impact. OBJETIVE: To describe the changes in clinical outcomes after the implementation of an antibiotic stewardship program in a level IV hospital. MATERIALS AND METHODS: We conducted a unique cohort study of patients hospitalized for infectious pathologies that were treated with antibiotics in an advanced medical facility. We collected the clinical history before the implementation of the antibiotic stewardship program (2013 to 2015) and then we compared it to the records from 2018 to 2019 collected after the implementation of the program. We evaluated changes in clinical outcomes such as overall mortality, and hospital stay, among others. RESULTS: We analyzed 1,066 patients: 266 from the preimplementation group and 800 from the post-implementation group. The average age was 59.2 years and 62% of the population was male. Statistically significant differences were found in overall mortality (29% vs 15%; p<0.001), mortality due to infectious causes (25% vs 9%; p<0.001), and average hospital stay (45 days vs 21 days; p<0.001); we also observed a tendency to decrease hospital readmission at 30 days for infectious causes (14% vs 10%; p=0.085). CONCLUSIONS: The antibiotic stewardship program implemented was associated with a decrease in overall mortality and mortality due to infectious causes, as well as in average hospital stay. Our results evidenced the importance of interventions aimed at mitigating the impact of inadequate prescription of antibiotics.

Introducción: La inadecuada prescripción de antibióticos es un problema de salud pública, reconocido por la Organización Mundial de la Salud. Los programas de gestión de antibióticos son implementados como una herramienta para mitigar su impacto. Objetivo: Describir los cambios observados en los desenlaces clínicos después de la implementación de un programa de gestión de antibióticos en un hospital de IV nivel de atención. Materiales y métodos. Se llevó a cabo un estudio de cohorte única de pacientes hospitalizados por patologías infecciosas y tratados con antibióticos en una institución médica de alta complejidad. Inicialmente, se recolectaron las historias clínicas anteriores a a la implementación del programa de gestión de antibióticos (2013 a 2015) y luego se compararon con los datos obtenidos después de la implementación del programa de gestión de antibióticos de 2018 a 2019. Se evaluaron los cambios en los desenlaces clínicos como mortalidad y estancia hospitalaria, entre otros. Materiales y métodos: Se llevó a cabo un estudio de cohorte única de pacientes hospitalizados por patologías infecciosas y tratados con antibióticos en una institución médica de alta complejidad. Inicialmente, se recolectaron las historias clínicas anteriores a a la implementación del programa de gestión de antibióticos (2013 a 2015) y luego se compararon con los datos obtenidos después de la implementación del programa de gestión de antibióticos de 2018 a 2019. Se evaluaron los cambios en los desenlaces clínicos como mortalidad y estancia hospitalaria, entre otros. Resultados: Se analizaron las historias clínicas de 1.066 pacientes: 266 con historia previa a la implementación del programa y 800 con historia posterior a la implementación. El promedio de edad fue 59,2 años y 62 % de la población era masculina. Se encontraron diferencias estadísticamente significativas en mortalidad global (29 Vs. 15 %; p<0,001), mortalidad por causa infecciosa (25 % Vs. 9 %; p<0,001) y promedio de estancia hospitalaria (45 Vs.21 días; p<0,001), con tendencia a disminuir nuevas hospitalizaciones en 30 días por patología infecciosa (14 Vs.10 %; p=0,085). Conclusiones: El desarrollo del programa de gestión de antibióticos se asoció con a una disminución en la mortalidad global, la mortalidad por causa infecciosa y la estancia hospitalaria. Esto demuestra la importancia de desarrollar intervenciones dirigidas a mitigar el impacto de la prescripción inadecuada de antibióticos.

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Aim: To evaluate the impact of the first year of the COVID-19 pandemic on antibiotic dispensation in three Brazilian hospitals. Methods: Stock movement was accessed from pharmacy databases and microbiological reports from 2018 to 2021. Results: Reduced antibiotic dispensation occurred during 2020 in all hospitals. The most significant reduction was in April at Hospital Doutor Jayme dos Santos Neves (∼58%), and in May at Hospital Doutor Roberto Arnizaut Silvares (∼66%) and Hospital Doutor Dório Silva (∼29%). However, azithromycin dispensation increased in all hospitals in 2020. Macrolide-resistant bacterial isolates rose from 66.6% in 2019 to 77.1% in 2020 and 88.3% in 2021. Conclusion: Despite reduced antibiotic dispensation, the increase in azithromycin consumption in 2020 highlights the urgency to monitor macrolide resistance after the pandemic and improve stewardship activities.

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The aim of this study was to develop an experimental composite resin with the addition of myristyltrimethylammonium bromide (MYTAB) and α -tricalcium phosphate (α-TCP) as an antibacterial and remineralizing material. Experimental composite resins composed of 75 wt% Bisphenol A-Glycidyl Methacrylate (BisGMA) and 25 wt% Triethylene Glycol Dimethacrylate (TEGDMA) were produced. Some 1 mol% Trimethyl benzoyl-diphenylphosphine oxide (TPO) was used as a photoinitiator, and butylated hydroxytoluene (BTH) was added as a polymerization inhibitor. Silica (1.5 wt%) and barium glass (65 wt%) particles were added as inorganic fillers. For remineralizing and antibacterial effect, α-TCP (10 wt%) and MYTAB (5 wt%) were incorporated into the resin matrix (α-TCP/MYTAB group). A group without the addition of α-TCP/MYTAB was used as a control. Resins were evaluated for their degree of conversion (n = 3) by Fourier Transform Infrared Spectroscopy (FTIR). The flexural strength (n = 5) was assessed based on ISO 4049:2019 requirements. Microhardness was assessed to calculate softening in solvent (n = 3) after ethanol immersion. The mineral deposition (n = 3) was evaluated after immersion in SBF, while cytotoxicity was tested with HaCaT cells (n = 5). Antimicrobial activity (n = 3) was analyzed against S. mutans. The degree of conversion was not influenced by the antibacterial and remineralizing compounds, and all groups reached values > 60%. The α-TCP/MYTAB addition promoted increased softening of polymers after immersion in ethanol and reduced their flexural strength and the viability of cells in vitro. A reduction in S. mutans viability was observed for the α-TCP/MYTAB group in biofilm formation and planktonic bacteria, with an antibacterial effect > 3log10 for the developed materials. Higher intensity of phosphate compounds on the sample's surface was detected in the α-TCP/MYTAB group. The addition of α-TCP and MYTAB promoted remineralizing and antibacterial effects on the developed resins and may be a strategy for bioactive composites.