RESUMO

OBJECTIVE: Increased mupirocin use leads to mupirocin resistance and is associated with persistence of methicillin-resistant Staphylococcus aureus (MRSA) carriers, prolonged hospitalization, and significant economic burdens for health systems. The study aimed to investigate the antimicrobial activity of compounds of Salvia rosmarinus L. ("rosemary", formerly Rosmarinus officinalis), alone or in combination with mupirocin, against multidrug resistant MRSA using isolates obtained from pediatric patients. METHODS: The in vitro antibacterial activity of the monoterpene α-pinene (α-Pi), a rosemary essential oil constituent, alone and in combination with mupirocin, was evaluated by determining the minimum inhibitory concentrations and minimum bactericidal concentrations (MBCs) and the fractional inhibitory concentration indices (FICIs) and fractional bactericidal concentration indices against multidrug-resistant clinical MRSA strains. The in vivo efficacy of α-Pi, alone and in combination with mupirocin, to eradicate MRSA infection was determined using an optimized mouse model of MRSA-infected wounds. Mouse skin samples (obtained via biopsy) were assessed for toxicity, and rabbit skin samples for irritation. RESULTS: Both in vitro and in vivo, α-Pi was active against MRSA strains and acted synergistically with mupirocin against MRSA strains. Mupirocin-monoterpene combinations exhibited FICI values of 0.2 to 0.4, reducing the MBC of topical mupirocin 33-fold. A topical formulation containing α-Pi and mupirocin enhanced the efficacy of mupirocin in an in vivo MRSA-infected mouse skin model without significantly harming the skin of mice and rabbits. CONCLUSIONS: A topical formulation combining mupirocin and α-Pi may aid in the development of innovative agents for treating MRSA infections.

Assuntos

Antibacterianos , Monoterpenos Bicíclicos , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Quimioterapia Combinada , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Mupirocina , Mupirocina/administração & dosagem , Mupirocina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Camundongos , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Monoterpenos Bicíclicos/administração & dosagem , Monoterpenos Bicíclicos/farmacologia , Humanos , Monoterpenos/farmacologia , Monoterpenos/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Modelos Animais de Doenças , Feminino

RESUMO

Background: Staphylococcus aureus infections are a significant cause of morbidity and mortality in pediatric populations worldwide. The Staphylo Research Network conducted an extensive study on pediatric patients across Colombia from 2018 to 2021. The aim of this study was to describe the epidemiological and microbiological characteristics of S. aureus in this patient group. Methods: We analyzed S. aureus isolates from WHONET-reporting centers. An "event" was a positive culture isolation in a previously negative individual after 2 weeks. We studied center characteristics, age distribution, infection type, and antibiotic susceptibilities, comparing methicillin sensitive (MSSA) and resistant S. aureus (MRSA) isolates. Results: Isolates from 20 centers across 7 Colombian cities were included. Most centers (80%) served both adults and children, with 55% offering oncology services and 85% having a PICU. We registered 8,157 S. aureus culture isolations from 5,384 events (3,345 MSSA and 1,961 MRSA) in 4,821 patients, with a median age of 5 years. Blood (26.2%) and skin/soft tissue (18.6%) were the most common infection sources. Most isolates per event remained susceptible to oxacillin (63.2%), clindamycin (94.3%), and TMP-SMX (98.3%). MRSA prevalence varied by city (<0.001), with slightly higher rates observed in exclusively pediatric hospitals. In contrast, the MRSA rate was somewhat lower in centers with Antimicrobial Stewardship Program (ASP). MRSA was predominantly isolated from osteoarticular infections and multiple foci, while MSSA was more frequently associated with recurrent infections compared to MRSA. Conclusions: This is the largest study of pediatric S. aureus infections in Colombia. We found MSSA predominance, but resistance have important regional variations. S. aureus remains susceptible to other commonly used antibiotics such as TMP-SMX and clindamycin. Ongoing monitoring of S. aureus infections is vital for understanding their behavior in children. Prospective studies within the Staphylored LATAM are underway for a more comprehensive clinical and genetic characterization.

RESUMO

Antimicrobial resistance (AMR) is one of the biggest threats in modern times. It was estimated that in 2019, 1.27 million deaths occurred around the globe due to AMR. Methicillin-resistant Staphylococcus aureus (MRSA) strains, a pathogen considered of high priority by the World Health Organization, have proven to be resistant to most of the actual antimicrobial treatments. Therefore, new treatments are required to be able to manage this increasing threat. Under this perspective, an important metabolic pathway for MRSA survival, and absent in mammals, is the shikimate pathway, which is involved in the biosynthesis of chorismate, an intermediate for the synthesis of aromatic amino acids, folates, and ubiquinone. Therefore, the enzymes of this route have been considered good targets to design novel antibiotics. The fifth step of the route is performed by shikimate kinase (SK). In this study, an in-house chemical library of 170 benzimidazole derivatives was screened against MRSA shikimate kinase (SaSK). This effort led to the identification of the first SaSK inhibitors, and the two inhibitors with the greatest inhibition activity (C1 and C2) were characterized. Kinetic studies showed that both compounds were competitive inhibitors with respect to ATP and non-competitive for shikimate. Structural analysis through molecular docking and molecular dynamics simulations indicated that both inhibitors interacted with ARG113, an important residue involved in ATP binding, and formed stable complexes during the simulation period. Biological activity evaluation showed that both compounds were able to inhibit the growth of a MRSA strain. Mitochondrial assays showed that both compounds modify the activity of electron transport chain complexes. Finally, ADMETox predictions suggested that, in general, C1 and C2 can be considered as potential drug candidates. Therefore, the benzimidazole derivatives reported here are the first SaSK inhibitors, representing a promising scaffold and a guide to design new drugs against MRSA.

Assuntos

Benzimidazóis , Staphylococcus aureus Resistente à Meticilina , Simulação de Acoplamento Molecular , Fosfotransferases (Aceptor do Grupo Álcool) , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/enzimologia , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/química , Benzimidazóis/farmacologia , Benzimidazóis/química , Cinética , Antibacterianos/farmacologia , Antibacterianos/química , Simulação de Dinâmica Molecular , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Humanos , Testes de Sensibilidade Microbiana , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química

RESUMO

Mastitis is the most common disease of dairy cattle and can be manifested in clinical and subclinical forms. The overuse of antimicrobials in the treatment and prevention of mastitis favours antimicrobial resistance and milk can be a potential route of dissemination. This study aimed to evaluate the biological quality of bulk tank milk (BTM) and the microbiological quality and signs of mastitis of freshly milked raw milk. In addition, to evaluate antimicrobial resistance in Enterobacteriaceae and Staphylococcus spp. isolated from freshly milked raw milk. None of the farms were within the official Brazilian biological quality limits for BTM. Freshly milked raw milk with signs of clinical (CMM), subclinical (SCMM) and no signs (MFM) of mastitis were detected in 6.67%, 27.62% and 65.71% samples, respectively. Most samples of freshly milked raw milk showed acceptable microbiological quality, when evaluating the indicators total coliforms (78.10%), Escherichia coli (88.57%) and Staphylococcus aureus (100%). Klebsiella oxytoca and S. aureus were the most prevalent microorganisms in SCMM and MFM samples. Antimicrobial resistance and multidrug resistance (MDR) were observed in 65.12% and 13.95% of Enterobacteriaceae and 84.31% and 5.88% of Staphylococcus spp., respectively, isolated from both SCMM and MFM samples. Enterobacteriaceae resistant to third-generation cephalosporin (3GCR) (6.98%) and carbapenems (CRE) (6.98%) and methicillin-resistant S. aureus (MRSA) (4.88%) were observed. Antimicrobial-resistant bacteria can spread resistance genes to previously susceptible bacteria. This is a problem that affects animal, human and environmental health and should be evaluated within the one-health concept.

Assuntos

Antibacterianos , Farmacorresistência Bacteriana , Enterobacteriaceae , Mastite Bovina , Leite , Staphylococcus , Animais , Bovinos , Leite/microbiologia , Mastite Bovina/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Feminino , Staphylococcus/efeitos dos fármacos , Brasil , Antibacterianos/farmacologia , Infecções por Enterobacteriaceae/veterinária , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções Estafilocócicas/veterinária , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Assintomáticas , Testes de Sensibilidade Microbiana/veterinária

RESUMO

Vancomycin is the cornerstone in treating methicillin-resistant Staphylococcus aureus (MRSA) infections. However, therapeutic failures can occur when MRSA strains with decreased susceptibility to glycopeptides (DSG) are involved. The aim of this study was to detect and characterize DSG in MRSA recovered from children with invasive diseases at a reference pediatric hospital between 2009 and 2019. Fifty-two MRSA strains were screened using agar plates with vancomycin 3 and 4 mg/L (BHI-3 and BHI-4); the VITEK2 system; and standard and macro E-tests. Suspicious hVISA were studied by population analysis profiling-area under the curve (PAP-AUC), and wall thickness was analyzed by transmission electron microscopy. Neither VRSA nor VISA were detected in this set. As only three strains met the hVISA criteria, the PAP-AUC study included 12 additional MRSA strains that grew one colony on BHI-4 plates or showed minimum inhibitory concentrations of vancomycin and/or teicoplanin ≥ 1.5 mg/L. One strain was confirmed as hVISA by PAP-AUC. The wall thickness was greater than the vancomycin-susceptible control strain; it belonged to ST30 and carried SCCmec IV. As expected, a low frequency of hVISA was found (1.9%). The only hVISA confirmed by PAP-AUC was not detected by the screening methods, highlighting the challenge that its detection represents for microbiology laboratories.

RESUMO

Photodynamic therapy (PDT) has been based on using photosensitizers (PS) and applying light of a specific wavelength. When this technique is used for treating infections, it is known as antimicrobial photodynamic therapy (aPDT). Currently, the use of lighting sources for in vitro studies using aPDT is generally applied in multiwell cell culture plates; however, depending on the lighting arrangement, there are usually errors in the application of the technique because the light from a well can affect the neighboring wells or it may be that not all the wells are used in the same experiment. In addition, one must be awarded high irradiance values, which can cause unwanted photothermal problems in the studies. Thus, this manuscript presents an in vitro antimicrobial photodynamic therapy for a Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) inhibition study using an arrangement of thermally isolated and independently illuminated green light source systems for eight tubes in vitro aPDT, determining the effect of the following factors: (i) irradiance level, (ii) exposure time, and (iii) Rose Bengal (RB) concentration (used as a PS), registering the Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) inhibition rates. The results show that in the dark, RB had a poor antimicrobial rate for P. aeruginosa, finding the maximum inhibition (2.7%) at 30 min with an RB concentration of 3 µg/mL. However, by applying light in a correct dosage (time × irradiance) and the adequate RB concentration, the inhibition rate increased by over 37%. In the case of MRSA, there was no significant inhibition with RB in complete darkness and, in contrast, the rate was 100% for those experiments that were irradiated.

RESUMO

Multidrug resistance in bacteria is a major challenge worldwide, increasing both mortality by infections and costs for the health systems. Therefore, it is of utmost importance to find new drugs against resistant bacteria. Beauvericin (BEA) is a mycotoxin produced by entomopathogenic and other fungi of the genus Fusarium. Our work determines the effect of BEA combined with antibiotics, which has not been previously explored. The combination analysis included different antibiotics against non-methicillin-resistant Staphylococcus aureus (NT-MRSA), methicillin-resistant Staphylococcus aureus (MRSA), and Salmonella typhimurium. BEA showed a synergy effect with oxacillin with a fractional inhibitory concentration index (FICI) = 0.373 and an additive effect in combination with lincomycin (FICI = 0.507) against MRSA. In contrast, it was an antagonist when combined with ciprofloxacin against S. typhimurium. We propose BEA as a molecule with the potential for the development of new therapies in combination with current antibiotics against multidrug-resistant bacteria.

Assuntos

Antibacterianos , Depsipeptídeos , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Salmonella typhimurium , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Depsipeptídeos/farmacologia , Sinergismo Farmacológico , Farmacorresistência Bacteriana Múltipla

RESUMO

Objective: To determine the risk factors associated with therapeutic failure of vancomycin in hospitalized adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infections. Design: Case-control study. Setting: Conducted in a high complexity hospital in Cali, Colombia. Participants: Adult hospitalized from January 1, 2015, to December 31, 2021, with MRSA infections with confirmed microbiological isolation. Methods: Cases were patients with therapeutic failure of vancomycin (mortality, poor clinical improvement, change of antibiotic used, early relapse, or persistence of positive blood cultures) and control patients were those who did not present failure. Significant variables from the bivariate analysis were included in a multiple analysis with an asymmetric logistic regression model. Results: A total of 105 patients were included in the study, 28 in the treatment group and 77 in the control group. The median age was 49 years and 59 (56%) of participants were men. The following variables: age (OR 1.034; 95% CI 1.007-1.061, p=0.011), osteomyelitis/ septic arthritis (OR 6.035; 95% CI 2.282-15.956, p=0.000) and minimum inhibitory concentration (MIC) (OR 5.971; 95% CI 1.321-26.979, p=0.020) were found to be independent risk factors associated with therapeutic failure of vancomycin. Vancomycin trough levels were not different between cases and controls (OR 0.976; 95% CI 0.911-1.044, p=0.478). Conclusions: When a multiple analysis was performed to control for confounding factors, only 3 variables were found to be significant and were considered risk factors for therapeutic failure of vancomycin in adult patients with MRSA infection: age, MIC, and osteomyelitis/ septic arthritis.

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of skin and soft tissue infections worldwide. This microorganism has a wide range of antibiotics resistance, a fact that has made the treatment of infections caused by MRSA difficult. In this sense, antimicrobial photodynamic therapy (aPDT) with natural products has emerged as a good alternative in combating infections caused by antibiotic-resistant microorganisms. The objective of the present study was to evaluate the effects of aPDT with Brazilian green propolis against intradermal MRSA infection in a murine model. Initially, 24 Balb/c mice were infected intradermally in the ears with 1.5 × 108 colony-forming units of MRSA 43300. After infection, they were separated into 4 groups (6 animals per group) and treated with the vehicle, only Brazilian green propolis, only blue LED light or with the aPDT protocol (Brazilian green propolis + blue LED light). It was observed in this study that aPDT with Brazilian green propolis reduced the bacterial load at the site of infection. Furthermore, it was able to inhibit weight loss resulting from the infection, as well as modulate the inflammatory response through greater recruitment of polymorphonuclear cells/neutrophils to the infected tissue. Finally, aPDT induced an increase in the cytokines IL-17A and IL-12p70 in the draining retromaxillary lymph node. Thus, aPDT with Brazilian green propolis proved to be effective against intradermal MRSA infection in mice, reducing bacterial load and modulating the immune response in the animals. However, more studies are needed to assess whether such effects are repeated in humans.

Assuntos

Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Própole , Humanos , Camundongos , Animais , Própole/farmacologia , Modelos Animais de Doenças , Brasil , Fotoquimioterapia/métodos , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química

RESUMO

Staphylococcus aureus infections are a severe health problem due to the high mortality rate. Conventional treatment of these infections is via the administration of antibiotics. However, its indiscriminate use can select resistant microorganisms. Thus, it is necessary to develop alternatives for antibiotic therapy. Antimicrobial Photodynamic Therapy (aPDT), a therapeutic method that associates a photosensitizer (PS), a light source with adequate wavelength to the PS, interacts with molecular oxygen generating reactive oxygen species responsible for cell inactivation, is a viable alternative. This work aimed to analyze, in vitro and in vivo, the action of aPDT with PS Photodithazine® (PDZ) on the methicillin-resistant S. aureus (MRSA) strain. In the in vitro method, the S. aureus biofilm was incubated with PDZ at 50 and 75 µg.mL-1 for 15 min, adopting the light dose of 25, 50, and 100 J/cm2. In addition, PS interaction, formation of reactive oxygen species (ROS), bacterial metabolism, adhesion, bacterial viability, and biofilm structure were evaluated by scanning electron microscopy. Subsequently, the strain was inoculated into models of Galleria mellonella, and the survival curve, health scale, blood cell analysis, and CFU/mL of S. aureus in the hemolymph were analyzed after aPDT. In the in vitro results, bacterial reduction was observed in the different PDZ concentrations, highlighting the parameters of 75 µg.mL-1 of PDZ and 100 J/cm2. As for in vivo results, aPDT increased survival and stimulated the immune system of G. mellonella infected by S. aureus. aPDT proved effective in both models, demonstrating its potential as an alternative therapy in treating MRSA bacterial infections.

Assuntos

Anti-Infecciosos , Glucosamina/análogos & derivados , Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Animais , Staphylococcus aureus , Espécies Reativas de Oxigênio/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Anti-Infecciosos/farmacologia , Biofilmes , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Modelos Teóricos

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major human pathogens. It could carry numerous resistance genes and virulence factors in its genome, some of which are related to the severity of the infection. An observational, descriptive, cross-sectional study was designed to molecularly analyze MRSA isolates that cause invasive infections in Paraguayan children from 2009 to 2013. Ten representative MRSA isolates of the main clonal complex identified were analyzed with short-read paired-end sequencing and assessed for the virulome, resistome, and phylogenetic relationships. All the genetically linked MRSA isolates were recovered from diverse clinical sources, patients, and hospitals at broad gap periods. The pan-genomic analysis of these clones revealed three major and different clonal complexes (CC30, CC5, and CC8), each composed of clones closely related to each other. The CC30 genomes prove to be a successful clone, strongly installed and disseminated throughout our country, and closely related to other CC30 public genomes from the region and the world. The CC5 shows the highest genetic variability, and the CC8 carried the complete arginine catabolic mobile element (ACME), closely related to the USA300-NAE-ACME+, identified as the major cause of CA-MRSA infections in North America. Multiple virulence and resistance genes were identified for the first time in this study, highlighting the complex virulence profiles of MRSA circulating in the country. This study opens a wide range of new possibilities for future projects and trials to improve the existing knowledge on the epidemiology of MRSA circulating in Paraguay. IMPORTANCE: The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is a public health problem worldwide. The most frequent MRSA clones identified in Paraguay in previous studies (including community and hospital acquired) were the Pediatric (CC5-ST5-IV), the Cordobes-Chilean (CC5-ST5-I), the SouthWest Pacific (CC30-ST30-IV), and the Brazilian (CC8-ST239-III) clones. In this study, the pan-genomic analysis of the most representative MRSA clones circulating in invasive infection in Paraguayan children over the years 2009-2013, such as the CC30-ST30-IV, CC5-ST5-IV, and CC8-ST8-IV, was carried out to evaluate their genetic diversity, their repertoire of virulence factors, and antimicrobial resistance determinants. This revealed multiple virulence and resistance genes, highlighting the complex virulence profiles of MRSA circulating in Paraguay. Our work is the first genomic study of MRSA in Paraguay and will contribute to the development of genomic surveillance in the region and our understanding of the global epidemiology of this pathogen.

Assuntos

Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Criança , Infecções Estafilocócicas/tratamento farmacológico , Filogenia , Estudos Transversais , Paraguai/epidemiologia , Genômica , Fatores de Virulência/genética , Células Clonais , Testes de Sensibilidade Microbiana , Antibacterianos/uso terapêutico

RESUMO

The rise of antibiotic-resistant bacteria calls for innovative approaches to combat multidrug-resistant strains. Here, the potential of the standard histological stain, Giemsa, to act as a photosensitizer (PS) for antimicrobial photodynamic inactivation (aPDI) against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) strains is reported. Bioassays were performed using various Giemsa concentrations (ranging from 0.0 to 20.0 µM) under 625 nm illumination at a light dose of 30 J cm-2. Remarkably, Giemsa completely inhibited the growth of MSSA and MRSA bacterial colonies for concentrations at 10 µM and higher but exhibited no inhibitory effect without light exposure. Partition coefficient analysis revealed Giemsa's affinity for membranes. Furthermore, we quantified the production of reactive oxygen species (ROS) and singlet oxygen (1O2) to elucidate the aPDI mechanisms underlying bacterial inactivation mediated by Giemsa. These findings highlight Giemsa stain's potential as a PS in aPDI for targeting multidrug-resistant bacteria.

Assuntos

Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Infecções Estafilocócicas , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Corantes Azur/farmacologia , Corantes Azur/uso terapêutico , Fotoquimioterapia/métodos , Staphylococcus aureus , Anti-Infecciosos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico

RESUMO

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.

RESUMO

Since the mid-2000s, livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has been identified among pigs worldwide, CC398 being the most relevant LA-MRSA clone. In the present work, nasal swabs were taken from healthy pigs of different age categories (25 to 154 days) from 2019 to 2021 in four intensive farms located in three provinces of Argentina. The aim of the present study was to characterize the first LA-MRSA isolates that colonized healthy fattening pigs in Argentina in terms of their resistance phenotype and genotype and to know the circulating clones in the country. Antimicrobial susceptibility, presence of the mecA gene and PCR screening of CC398 were evaluated in all the isolates. They were resistant to cefoxitin, penicillin, tetracycline, chloramphenicol and ciprofloxacin but susceptible to nitrofurantoin, rifampicin, vancomycin and linezolid. Furthermore, 79% were resistant to clindamycin and lincomycin, 68% to erythromycin, 58% to gentamicin and 37% to trimethoprim/sulfamethoxazole. All the isolates were multidrug resistant. The clonal relation was assessed by SmaI-PFGE (pulsed-field gel electrophoresis) and a representative isolate of each PFGE type was whole genome sequenced by Illumina. MLST (multilocus sequence typing), resistance and virulence genes and SCCmec typing were performed on sequenced isolates. The isolates were differentiated in three clonal types by PFGE, and they belonged to sequence-type ST398 (58%) and ST9, CC1 (42%) by MLST. SCCmec typeV and several resistance genes detected showed complete correlation with resistance phenotypes. The present study revealed that LA-MRSA colonizing healthy pigs in Argentina belongs to CC398 and CC1, two MRSA lineages frequently associated to pigs in other countries.

RESUMO

El síndrome de compresión medular es una urgencia neuroquirúrgica debido a que un diagnóstico precoz y un tratamiento temprano podría revertir las incapacitantes secuelas ocasionadas por esta enfermedad. Las causas de este síndrome pueden ser traumática, metastásica, infecciosa y vascular (hematomas). La etiología infecciosa no es frecuente y el principal germen involucrado suele ser Staphylococcus aureus. A continuación presentamos el caso de una paciente de 58 años con síndrome de compresión medular de etiología infecciosa quien fue ingresada en el Servicio de Clínica Médica del Centro Médico Nacional.

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Spinal cord compression syndrome is a neurosurgical emergency because early diagnosis and early treatment could reverse the disabling consequences caused by this disease. The causes of this syndrome can be traumatic, metastatic, infectious, and vascular (hematomas). Infectious etiology is not frequent and the main germ involved is usually Staphylococcus aureus. Below we present the case of a 58-year-old patient with spinal cord compression syndrome of infectious etiology who was admitted to the Medical Clinic Service of the National Medical Center.

RESUMO

Backgrounds: Both healthcare-associated and community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections are relevant in children. The objective of our study was to evaluate their impact in a pediatric hospital in southern Brazil. Methods: Data from patients under 18 years of age with S. aureus infections between January 2013 and December 2020 were retrospectively analyzed. Data were collected regarding infection site, infection type (community-acquired or healthcare-associated), susceptibility to oxacillin [methicillin-susceptible S. aureus (MSSA) or MRSA] and other antimicrobials. We analyzed the evolution of the susceptibility rates for the isolates over this period. Results: A total of 563 patients were included, among whom the prevalences of community- and hospital-acquired MRSA infections were 46.1% and 8.1%, respectively. No significant change occurred in these prevalences over the study period. In community-acquired infections, MSSA was significantly more associated with osteoarticular infections and MRSA was more associated with respiratory and intra-abdominal infections. In healthcare-associated infections, there was an association between MSSA and primary bloodstream infections and between MRSA, skin/soft tissue infections, and respiratory infections. Community-acquired MRSA were highly susceptible to trimethoprim-sulfamethoxazole (96.1%), clindamycin (88.4%), and doxycycline (99.0%). Conclusion: Our study draws attention to the high rates of MRSA in community-acquired staphylococcal infections in this population, indicating a need to review initial protocols for severe staphylococcal infections according to local epidemiology.

RESUMO

Resistance to antibacterial agents is a growing global public health problem that reduces the efficacy of available antibacterial agents, leading to increased patient mortality and morbidity. Unfortunately, only 16 antibacterial drugs have been approved by the FDA in the last 10 years, so it is necessary to develop new agents with novel chemical structures and/or mechanisms of action. In response to this, our group takes up the challenge of designing a new family of pyrimidoisoquinolinquinones displaying antimicrobial activities against multidrug-resistant Gram-positive bacteria. Accordingly, the objective of this study was to establish the necessary structural requirements to obtain compounds with high antibacterial activity, along with the parameters controlling antibacterial activity. To achieve this goal, we designed a family of compounds using different strategies for drug design. Forty structural candidates were synthesized and characterized, and antibacterial assays were carried out against high-priority bacterial pathogens. A variety of structural properties were modified, such as hydrophobicity and chain length of functional groups attached to specific carbon positions of the quinone core. All the synthesized compounds inhibited Gram-positive pathogens in concentrations ranging from 0.5 to 64 µg/mL. Two derivatives exhibited minimum inhibitory concentrations of 64 µg/mL against Klebsiella pneumoniae, while compound 28 demonstrated higher potency against MRSA than vancomycin.

RESUMO

Wounds of an acute or chronic etiology affect millions of people worldwide, with increasing prevalence every year. Microbial infections are one of the main causes that impair the wound healing process, and Staphylococcus aureus, a commensal member of the skin microbiota, is one of the main causative agents of wound infections. Crucially, a high proportion of these infections are caused by methicillin-resistant Staphylococcus aureus, which, in addition to ß-lactams, has acquired resistance to almost all the antibacterial agents used to treat it, limiting therapeutic options. Studies on the antimicrobial and healing activities of extracts, essential oils, or metabolites obtained from native plants have been reported in many countries that have a diverse flora and traditions with the use of medicinal plants for the treatment of wound infections. Due to their great chemical diversity, plants have proven to be promising sources of bioactive molecules for the discovery and development of new drugs or strategies for the treatment of wounds. This review highlights the main herbal preparations that have antimicrobial and healing activities with potential for the treatment of wound infections caused by Staphylococcus aureus.

RESUMO

OBJETIVOS: El objetivo primario de este estudio fue determinar la prevalencia de colonización nasal por Staphylococcus aureus meticilino resistente (SAMR) en estudiantes de medicina en cursos pre-clínicos versus clínicos de la Pontificia Universidad Católica de Chile y describir el patrón epidemiológico, clínico y molecular de las cepas de SAMR obtenidas. PACIENTES Y MÉTODO: Se realizó un estudio descriptivo transversal a 299 estudiantes de pregrado y postgrado de medicina de la Pontificia Universidad Católica de Chile, 44 alumnos de primer año y 29 de segundo año, correspondiendo éstos a alumnos de cursos sin exposición clínica habitual y 26 alumnos de sexto año, 58 de séptimo año y 142 residentes, los cuales están diariamente expuestos a ambientes hospitalarios. RESULTADOS: Se encontró una portación de 0% (0/73) en estudiantes no expuestos a la clínica (cursos pre-clínicos) y de 0,9% (2/226) en estudiantes de cursos clínicos, diferencia que no fue estadísticamente significativa (valor p 0,42). CONCLUSIONES: La portación nasal de SAMR en el personal de salud de este trabajo fue baja, encontrando muestras positivas solo en estudiantes con exposición clínica. Esta prevalencia es similar a la reportada en otros trabajos de características similares realizados en Chile.

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OBJECTIVES: The primary objective of this study was to determine the prevalence of nasal colonization of methicillin resistant Staphylococcus aureus (MRSA) in medical students in pre-clinical versus clinical courses at the Pontificia Universidad Católica de Chile and to describe the epidemiological, clinical and molecular pattern of the MRSA strains obtained. METHOD: A cross-sectional descriptive study was carried out on 299 undergraduate and graduate medical students from the Pontificia Universidad Católica de Chile, 44 first-year students and 29 second-year students, corresponding to students of courses without regular clinical exposure and 26 sixth-year students, 58 seventh-year and 142 residents, who are daily exposed to hospital environments. RESULTS: A carriage of 0% (0/73) was found in students not exposed to the clinic (pre-clinical courses) and 0.9% (2/226) in students of clinical courses, a difference that was not statistically significant (p-value 0.42). CONCLUSIONS: The MRSA nasal carriage found in our medical students was low, finding positive samples only in students with clinical exposure. This prevalence is similar to the one reported in other studies in Chile with similar characteristics.

Assuntos

Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/epidemiologia , Estudantes de Medicina/estatística & dados numéricos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Portador Sadio/microbiologia , Portador Sadio/epidemiologia , Chile/epidemiologia , Prevalência , Estudos Transversais , Cavidade Nasal/microbiologia

RESUMO

Polygonum hydropiperoides Michx. is an Asian native plant species that is also widely distributed in the Americas. Despite its traditional uses, P. hydropiperoides is scarcely scientifically exploited. This study aimed to chemically characterize and investigate the antioxidant and antibacterial activities of hexane (HE-Ph), ethyl acetate (EAE-Ph), and ethanolic (EE-Ph) extracts from aerial parts of P. hydropiperoides. The chemical characterization was performed through HPLC-DAD-ESI/MSn. The antioxidant activity was assessed by the phosphomolybdenum reducing power, nitric oxide inhibition, and the ß-carotene bleaching assays. The antibacterial activity was determined by the minimal inhibitory concentration (MIC) and the minimal bactericidal concentration followed by the classification of the antibacterial effect. Chemical characterization revealed the expressive presence of phenolic acids and flavonoids in EAE-Ph. An increased antioxidant capacity was revealed in EAE-Ph. Regarding antibacterial activity, EAE-Ph showed weak to moderate property against 13 strains tested with MIC values ranging from 625 to 5000 µg/mL, with bactericidal or bacteriostatic effects. Glucogallin and gallic acid stand out as the most relevant bioactive compounds. These results suggest that P. hydropiperoides is a natural source of active substances, supporting this species' traditional use.