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1.
ACS Appl Mater Interfaces ; 13(1): 155-163, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33356100

RESUMO

A substantial increase in the risk of hospital-acquired infections (HAIs) has greatly impacted the global healthcare industry. Harmful pathogens adhere to a variety of surfaces and infect personnel on contact, thereby promoting transmission to new hosts. This is particularly worrisome in the case of antibiotic-resistant pathogens, which constitute a growing threat to human health worldwide and require new preventative routes of disinfection. In this study, we have incorporated different loading levels of a porphyrin photosensitizer capable of generating reactive singlet oxygen in the presence of O2 and visible light in a water-soluble, photo-cross-linkable polymer coating, which was subsequently deposited on polymer microfibers. Two different application methods are considered, and the morphological and chemical characteristics of these coated fibers are analyzed to detect the presence of the coating and photosensitizer. To discern the efficacy of the fibers against pathogenic bacteria, photodynamic inactivation has been performed on two different bacterial strains, Staphylococcus aureus and antibiotic-resistant Escherichia coli, with population reductions of >99.9999 and 99.6%, respectively, after exposure to visible light for 1 h. In response to the current COVID-19 pandemic, we also confirm that these coated fibers can inactivate a human common cold coronavirus serving as a surrogate for the SARS-CoV-2 virus.


Assuntos
/virologia , Fármacos Fotossensibilizantes/farmacologia , Polímeros/farmacologia , /prevenção & controle , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Humanos , Doença Iatrogênica/prevenção & controle , Luz , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Microfibrilas/química , Pandemias , Fármacos Fotossensibilizantes/química , Polímeros/química , Porfirinas/química , Porfirinas/farmacologia , /patogenicidade , Oxigênio Singlete
2.
PLoS One ; 15(9): e0238991, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32946486

RESUMO

BACKGROUND: Invasive Staphylococcus aureus infections are a common cause of morbidity and mortality in children. In the early 2000's the proportion of infections due the methicillin-resistant S. aureus (MRSA) increased rapidly. We described the clinical and molecular epidemiology of invasive S. aureus disease in a pediatric population. METHODS: We prospectively identified children in Utah with invasive S. aureus infections. Medical records were reviewed to determine diagnosis and clinical characteristics. Isolates were genotyped using multi-locus sequence typing. The presence of genes encoding the Panton-Valentine leukocidin (PVL) was determined using polymerase chain reaction. RESULTS: Over a 4-year period between January 2009 and December 2012, we identified 357 children, hospitalized at Primary Children's Hospital, with invasive S. aureus infections and isolates available for the study. Methicillin-susceptible S. aureus (MSSA) caused 79% of disease, while MRSA caused only 21% of disease. Mortality associated with invasive S. aureus infection was 3.6%. The most common diagnoses were osteoarticular infections (38%) followed by central line associated blood stream infections (19%) and pneumonia (12%). We identified 41 multi-locus sequence types. The majority of isolates belonged to 6 predominant clonal complexes (CC5, CC8, CC15, CC30, CC45, CC59). PVL was present in a minority (16%) of isolates, of which most were ST8 MRSA. CONCLUSIONS: MSSA was the primary cause of invasive S. aureus infections at our institution throughout the study period. A limited number of predominant strains accounted for the majority of invasive disease. The classic virulence factor PVL was uncommon in MSSA isolates. Further study is needed to improve our understanding of S. aureus virulence and disease pathogenesis.


Assuntos
Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/genética , Antibacterianos/uso terapêutico , Técnicas de Tipagem Bacteriana/métodos , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Testes de Sensibilidade Microbiana , Epidemiologia Molecular/métodos , Tipagem de Sequências Multilocus/métodos , Infecções Estafilocócicas/genética , Staphylococcus aureus/patogenicidade , Utah/epidemiologia , Fatores de Virulência/genética
3.
Arch Microbiol ; 202(10): 2751-2760, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32737541

RESUMO

Staphylococcus aureus is an opportunistic pathogen that has the ability to cause a wide range of diseases including superficial infection and severe invasive life threatening infections. The pathogenicity of S. aureus is mediated by a group of virulence factors that mediate the colonization and penetration. The antibiotic resistance of S. aureus has evolved due to the abuse of antibiotics rendering the cure of infection very difficult especially with the shortage in new antibiotic production. To combat this shortage, repurposing of FDA-approved drugs against the virulence factors is a new strategy. The analgesic drug Diclofenac was found to have anti-virulence activity against Pseudomonas aeruginosa and Proteus mirabilis. This study aimed to demonstrate the anti-virulence effect of diclofenac against clinical MRSA isolates phenotypically and genotypically using qRT-PCR. In this study, diclofenac showed significant reduction in biofilm formation when compared to controls, the inhibition ranged between 22.67% and 70%. Also, remarkable inhibition of hemolysin activity was found (5.4-66.34%). Additionally, diclofenac has inhibitory activity against the staphyloxanthin production (8-57.2%). The results were confirmed by qRT-PCR that showed significant down-regulation of tested virulence genes. The down-regulation ranged from 43 to 64.05% for SarA, 36.85-64.75% for AgrA, 50-63.2% for hla, 38.55-60.35% for FnbA, 46.75-61.05% for IcaA, 27.55-64% for SigB and 51.05-72.8% for CrtM. In conclusion, diclofenac can be used in combination with antibiotics as anti-virulence agent against MDR-MRSA which will enhance the ability of immune system to eradicate infection.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Diclofenaco/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Farmacorresistência Bacteriana Múltipla/fisiologia , Genótipo , Proteínas Hemolisinas/antagonistas & inibidores , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Proteus mirabilis/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Virulência/genética , Fatores de Virulência/antagonistas & inibidores , Fatores de Virulência/genética , Xantofilas/antagonistas & inibidores
4.
PLoS One ; 15(8): e0237714, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804961

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious public health problem. There is limited information regarding the genetics of MRSA strains among the native Iraqi and incoming Syrian refugee communities. We aimed to characterize the genotypes and different virulence factors of MRSA in strains isolated from these two communities. Frozen MRSA strains (125) isolated from the native Iraqi and Syrian refugee communities were used in this study. PCR (singleplex and multiplex) and agr typing was used for the genotypic analysis of different virulence genes. We tested for the presence of virulence genes including pvl, arcA, tst, lukE/lukD, hla, hlb, eta, etb and agr. Prevalence of arcA MRSA in the Iraqi community (56.58%) was significantly higher (p = 0.008) than that in the Syrian refugee community (32.66%). Prevalence of lukE-lukD was also significantly higher (p = 0.001) in the Iraqi (82.89%) compared to that in the Syrian refugee community (57.14%). Further, prevalence of hla MRSA in the Iraqi community was (93.4%) and in the Syrian refugee community was (71.4%); (p = 0.0008). No significant differences were observed in the prevalence of pvl, tst, eta, etb and hlb. The most dominant agr types in both Iraqi (76.1% and 10.5%) and Syrian refugee (44.9% and 18.37%) communities were I and III. To sum up, no significant differences were observed between the groups for a majority of virulence factors. This is the first investigation of MRSA genotypes and virulence in both these communities. These results could be useful for further studies that assess the genetic relatedness of strains in the region for epidemiological and monitoring purposes, which would be crucial to limiting the spread of MRSA.


Assuntos
Resistência a Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Refugiados , Infecções Estafilocócicas/microbiologia , Fatores de Virulência/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/isolamento & purificação , Cidades/epidemiologia , Exotoxinas/genética , Exotoxinas/isolamento & purificação , Genes Bacterianos/genética , Técnicas de Genotipagem , Humanos , Iraque/epidemiologia , Meticilina/farmacologia , Meticilina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Prevalência , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Síria , Transativadores/genética , Transativadores/isolamento & purificação , Fatores de Virulência/isolamento & purificação
5.
PLoS One ; 15(8): e0237085, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32776958

RESUMO

BACKGROUND: Sepsis is the third most common cause of death among neonates, with about 225,000 newborns dying every year globally. Data concerning the microbial etiology of neonatal sepsis and antimicrobial resistance profiles of its causative agents are necessary to inform targeted and effective treatment and prevention strategies. OBJECTIVE: To determine the proportion of newborns with symptoms and signs of sepsis who had a positive blood culture, its bacterial etiology, the antimicrobial resistance patterns as well as the factors associated with culture-positivity and case fatality at Mulago national referral hospital in Uganda. METHODS: We conducted a cross-sectional study among 359 neonates with symptoms and signs of sepsis who presented to the pediatric emergency care unit of Mulago national referral hospital from mid-January to end of December 2018. We performed blood culture and antimicrobial susceptibility testing, and conducted polymerase chain reaction to identify methicillin-resistant Staphylococcus aureus (MRSA) isolates. We used multivariable logistic regression to estimate the association between potential risk factors and culture-positive neonatal sepsis. FINDINGS: Of the 359 neonates recruited, 46 (12.8%; 95% CI 9.5%, 16.7%) had a positive blood culture. The predominant isolated bacteria were Staphylococcus aureus in 29 (63.0%), Escherichia coli in seven (15.2%), and Klebsiella pneumoniae in five (10.9%). Of the 46 pathogens, 73.9% were resistant to ampicillin, 23.9% to gentamicin and 8.7% to ceftriaxone. We isolated MRSA from the blood specimens of 19 (5.3%) of the 359 neonates, while 3 (0.8%) grew extended spectrum beta lactamase producers. The case fatality risk among neonates with neonatal sepsis was 9.5% (95% CI: 6.6%, 13.0%). Cesarean section delivery was strongly associated with culture-positive sepsis (adjusted odds ratio 3.45, 95% CI: 1.2, 10.1). CONCLUSION: One in eight neonates with clinical signs of sepsis grew a likely causative bacterial pathogen. S. aureus was the main pathogen isolated and a third of these isolates were MRSA. A significant proportion of the isolated bacterial pathogens were resistant to the first and second line antibiotics used for the treatment of neonatal sepsis. There is need to revisit the current treatment guidelines for neonatal sepsis.


Assuntos
Sepse Neonatal/epidemiologia , Infecções Estafilocócicas/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Recém-Nascido , Masculino , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Sepse Neonatal/etiologia , Sepse Neonatal/microbiologia , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/microbiologia , Uganda
6.
Medicine (Baltimore) ; 99(26): e20914, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590802

RESUMO

RATIONALE: Methicillin-resistant Staphylococcus aureus (MRSA) has been established as an important cause of severe community-acquired pneumonia (CAP) with very high mortality. Panton-Valentine leukocidin (PVL) producing MRSA has been reported to be associated with necrotizing pneumonia and worse outcome. The incidence of community-acquired MRSA (CA-MRSA) pneumonia is very low, as only a few CA-MRSA pneumonia cases were reported in the last few years. We present a case of severe CAP caused by PVL-positive MRSA with ensuing septic shock. PATIENT CONCERNS: A 68-year-old male with no concerning medical history had developed a fever that reached 39.0°C, a productive cough that was sustained for 5 days, and hypodynamia. He was treated with azithromycin and alexipyretic in a nearby clinic for 2 days in which the symptoms were alleviated. However, 1 day later, the symptoms worsened, and he was taken to a local Chinese medicine hospital for traditional medicine treatment. However, his clinical condition deteriorated rapidly, and he then developed dyspnea and hemoptysis. DIAGNOSIS: CA-MRSA pneumonia and septic shock. The sputum culture showed MRSA. Polymerase chain reaction of MRSA isolates was positive for PVL genes. INTERVENTIONS: Mechanical ventilation, fluid resuscitation, and antibiotic therapy were performed. Antibiotic therapy included mezlocillin sodium/sulbactam sodium, linezolid, and oseltamivir. OUTCOMES: He died after 12 hours of treatment. LESSONS: This is a report of severe pneumonia due to PVL-positive CA-MRSA in a healthy adult. CA-MRSA should be considered a pathogen of severe CAP, especially when combined with septic shock in previously healthy individuals.


Assuntos
Pneumonia Associada a Assistência à Saúde/etiologia , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Infecções Estafilocócicas/complicações , Idoso , Antibacterianos/uso terapêutico , Tosse/etiologia , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Pneumonia Associada a Assistência à Saúde/microbiologia , Humanos , Hipocinesia/etiologia , Linezolida/uso terapêutico , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Mezlocilina/uso terapêutico , Oseltamivir/uso terapêutico , Choque Séptico/etiologia , Choque Séptico/mortalidade , Choque Séptico/fisiopatologia
7.
Proc Natl Acad Sci U S A ; 117(27): 15789-15798, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32581129

RESUMO

Patients infected with influenza are at high risk of secondary bacterial infection, which is a major proximate cause of morbidity and mortality. We have shown that in mice, prior infection with influenza results in increased inflammation and mortality upon Staphylococcus aureus infection, recapitulating the human disease. Lipidomic profiling of the lungs of superinfected mice revealed an increase in CYP450 metabolites during lethal superinfection. These lipids are endogenous ligands for the nuclear receptor PPARα, and we demonstrate that Ppara -/- mice are less susceptible to superinfection than wild-type mice. PPARα is an inhibitor of NFκB activation, and transcriptional profiling of cells isolated by bronchoalveolar lavage confirmed that influenza infection inhibits NFκB, thereby dampening proinflammatory and prosurvival signals. Furthermore, network analysis indicated an increase in necrotic cell death in the lungs of superinfected mice compared to mice infected with S. aureus alone. Consistent with this, we observed reduced NFκB-mediated inflammation and cell survival signaling in cells isolated from the lungs of superinfected mice. The kinase RIPK3 is required to induce necrotic cell death and is strongly induced in cells isolated from the lungs of superinfected mice compared to mice infected with S. aureus alone. Genetic and pharmacological perturbations demonstrated that PPARα mediates RIPK3-dependent necroptosis and that this pathway plays a central role in mortality following superinfection. Thus, we have identified a molecular circuit in which infection with influenza induces CYP450 metabolites that activate PPARα, leading to increased necrotic cell death in the lung which correlates with the excess mortality observed in superinfection.


Assuntos
Inflamação/genética , Influenza Humana/genética , PPAR alfa/genética , Infecções Estafilocócicas/genética , Superinfecção/genética , Animais , Lavagem Broncoalveolar/métodos , Coinfecção/genética , Coinfecção/microbiologia , Coinfecção/mortalidade , Sistema Enzimático do Citocromo P-450/genética , Modelos Animais de Doenças , Suscetibilidade a Doenças , Humanos , Inflamação/microbiologia , Inflamação/mortalidade , Influenza Humana/microbiologia , Influenza Humana/mortalidade , Pulmão/microbiologia , Pulmão/patologia , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos , Camundongos Knockout , Necroptose/genética , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Superinfecção/mortalidade
8.
Biochim Biophys Acta Biomembr ; 1862(8): 183282, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32376222

RESUMO

Antimicrobial peptides are considered promising candidates for the development of novel antimicrobial agents to combat infections by multi-drug-resistant (MDR) bacteria. Here, we describe the identification and characterization of the synthetic peptide TC19, derived from the human thrombocidin-1-derived peptide L3. Biophysical experiments into the interaction between TC19 and mimics of human and bacterial plasma membranes demonstrated that the peptide is highly selective for bacterial membranes. In agreement, TC19 combined low cytotoxicity towards human fibroblasts with efficient and rapid killing in human plasma of MDR strains of several bacterial species of the ESKAPE panel. In addition, TC19 induced minor resistance in vitro, neutralized pro-inflammatory activity of bacterial cell envelope components while displaying slight chemotactic activity for human neutrophils. Importantly, topical application of TC19-containing hypromellose gel significantly reduced numbers of viable methicillin-resistant Staphylococcus aureus (MRSA) and MDR Acinetobacter baumannii in a superficial wound infection in mice. Together, TC19 is an attractive candidate for further development as a novel agent against (MDR) bacterial skin wound infections.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Biofilmes/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Membrana Celular/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos , Pele/efeitos dos fármacos , Pele/microbiologia , Pele/patologia , Infecção dos Ferimentos/genética , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
9.
Biochim Biophys Acta Biomembr ; 1862(8): 183195, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32130974

RESUMO

The global health threat surrounding bacterial resistance has resulted in antibiotic researchers shifting their focus away from 'traditional' antibiotics and concentrating on other antimicrobial agents, including antimicrobial peptides. These low molecular weight "mini-proteins" exhibit broad-spectrum activity against bacteria, including multi-drug resistant strains, viruses, fungi and protozoa and constitute a major element of the innate-immune system of many multicellular organisms. Some naturally occurring antimicrobial peptides are lipidated and/or glycosylated and almost all antimicrobial peptides in clinical use are either lipopeptides (Daptomycin and Polymyxin E and B) or glycopeptides (Vancomycin). Lipidation, glycosylation and PEGylation are an option for improving stability and activity in serum and for reducing the rapid clearing via the kidneys and liver. Two broad-spectrum antimicrobial peptides NH2-RIRIRWIIR-CONH2 (A1) and NH2-KRRVRWIIW-CONH2 (B1) were conjugated via a linker, producing A2 and B2, to individual fatty acids of C8, C10, C12 and C14 and in addition, A2 was conjugated to either glucose, N-acetyl glucosamine, galactose, mannose, lactose or polyethylene glycol (PEG). Antimicrobial activity against two Gram-positive strains (methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecalis (VRE)) and three Gram-negative strains (Salmonella typhimurium, E. coli and Pseudomonas aeruginosa) were determined. Activity patterns for the lipidated versions are very complex, dependent on sequence, bacteria and fatty acid. Two reciprocal effects were measured; compared to the parental peptides, some combinations led to a 16-fold improvement whereas other combinations let to a 32-fold reduction in antimicrobial activity. Glycosylation decreased antimicrobial activity by 2 to 16-fold in comparison to A1, respectively on the sugar-peptide combination. PEGylation rendered the peptide inactive. Antimicrobial activity in the presence of 25% human serum of A1 and B1 was reduced 32-fold and 8-fold, respectively. The longer chain fatty acids almost completely restored this activity; however, these fatty acids increased hemolytic activity. B1 modified with C8 increased the therapeutic index by 2-fold for four bacterial strains. Our results suggest that finding the right lipid-peptide combination can lead to improved activity in the presence of serum and potentially more effective drug candidates for animal studies. Glycosylation with the optimal sugar and numbers of sugars at the right peptide position could be an alternative route or could be used in addition to lipidation to counteract solubility and toxicity issues.


Assuntos
Antibacterianos/efeitos adversos , Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Glicosilação/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Enterococos Resistentes à Vancomicina/patogenicidade
10.
Nature ; 579(7798): 260-264, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32132711

RESUMO

The production of pore-forming toxins that disrupt the plasma membrane of host cells is a common virulence strategy for bacterial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA)1-3. It is unclear, however, whether host species possess innate immune mechanisms that can neutralize pore-forming toxins during infection. We previously showed that the autophagy protein ATG16L1 is necessary for protection against MRSA strains encoding α-toxin4-a pore-forming toxin that binds the metalloprotease ADAM10 on the surface of a broad range of target cells and tissues2,5,6. Autophagy typically involves the targeting of cytosolic material to the lysosome for degradation. Here we demonstrate that ATG16L1 and other ATG proteins mediate protection against α-toxin through the release of ADAM10 on exosomes-extracellular vesicles of endosomal origin. Bacterial DNA and CpG DNA induce the secretion of ADAM10-bearing exosomes from human cells as well as in mice. Transferred exosomes protect host cells in vitro by serving as scavengers that can bind multiple toxins, and improve the survival of mice infected with MRSA in vivo. These findings indicate that ATG proteins mediate a previously unknown form of defence in response to infection, facilitating the release of exosomes that serve as decoys for bacterially produced toxins.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Toxinas Bacterianas/metabolismo , Exossomos/metabolismo , Células A549 , Proteína ADAM10/metabolismo , Animais , Toxinas Bacterianas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , DNA Bacteriano/farmacologia , Exossomos/efeitos dos fármacos , Exossomos/ultraestrutura , Feminino , Células HEK293 , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Staphylococcus aureus Resistente à Meticilina/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Infecções Estafilocócicas/mortalidade
12.
BMC Infect Dis ; 20(1): 160, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32085732

RESUMO

BACKGROUND: S. aureus (SA) infective endocarditis (IE) has a very high mortality, attributed to the age and comorbidities of patients, inadequate or delayed antibiotic treatment, and methicillin resistance, among other causes. The main study objective was to analyze epidemiological and clinical differences between IE by methicillin-resistant versus methicillin-susceptible SA (MRSA vs. MSSA) and to examine prognostic factors for SA endocarditis, including methicillin resistance and vancomycin minimum inhibitory concentration (MIC) values > 1 µg/mL to MRSA. METHODS: Patients with SA endocarditis were consecutively and prospectively recruited from the Andalusia endocarditis cohort between 1984 and January 2017. RESULTS: We studied 437 patients with SA endocarditis, which was MRSA in 13.5% of cases. A greater likelihood of history of COPD (OR 3.19; 95% CI 1.41-7.23), invasive procedures, or recognized infection focus in the 3 months before IE onset (OR 2.9; 95% CI 1.14-7.65) and of diagnostic delay (OR 3.94; 95% CI 1.64-9.5) was observed in patients with MRSA versus MSSA endocarditis. The one-year mortality rate due to SA endocarditis was 44.3% and associated with decade of endocarditis onset (1985-1999) (OR 8.391; 95% CI (2.82-24.9); 2000-2009 (OR 6.4; 95% CI 2.92-14.06); active neoplasm (OR 6.63; 95% CI 1.7-25.5) and sepsis (OR 2.28; 95% CI 1.053-4.9). Methicillin resistance was not associated with higher IE-related mortality (49.7 vs. 43.1%; p = 0.32). CONCLUSION: MRSA IE is associated with COPD, previous invasive procedure or recognized infection focus, and nosocomial or healthcare-related origin. Methicillin resistance does not appear to be a decisive prognostic factor for SA IE.


Assuntos
Antibacterianos/farmacologia , Endocardite Bacteriana/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Adulto , Idoso , Antibacterianos/uso terapêutico , Estudos de Coortes , Testes Diagnósticos de Rotina , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/epidemiologia , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/isolamento & purificação
13.
Value Health ; 23(1): 89-95, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31952677

RESUMO

BACKGROUND: Livestock-acquired methicillin-resistant Staphylococcus aureus (LA-MRSA) is a concern in healthcare and a political priority in some countries. OBJECTIVE: This study investigates the net societal costs of 2 alternative strategies for controlling LA-MRSA in Denmark: (1) eradicating LA-MRSA in all pig housing units, and (2) containing LA-MRSA within the units. METHODS: Benefits and costs are considered for affected economic sectors: healthcare, pig production, pig-related industries, and public administration. RESULTS: The cost to society of eradication is estimated at €2.3 to €2.5 billion (present value). Containment will cost €55 to €93 million. For both strategies, the main cost lies in primary pig production-for containment this is mainly due to establishing and operating anterooms and shower rooms, and for eradication it is due to production losses, loss of genetic resources, and costs of cleaning and disinfection. CONCLUSION: Compared with these costs, health economic benefits are moderate for both strategies. Containment is superior to eradication when measured by a benefit-cost ratio.


Assuntos
Contenção de Riscos Biológicos/veterinária , Erradicação de Doenças/economia , Custos de Cuidados de Saúde , Abrigo para Animais , Controle de Infecções/economia , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Infecções Estafilocócicas/veterinária , Doenças dos Suínos , Suínos/microbiologia , Zoonoses , Animais , Contenção de Riscos Biológicos/economia , Análise Custo-Benefício , Dinamarca , Humanos , Exposição Ocupacional/economia , Exposição Ocupacional/prevenção & controle , Medição de Risco , Fatores de Risco , Infecções Estafilocócicas/economia , Infecções Estafilocócicas/prevenção & controle , Infecções Estafilocócicas/transmissão , Doenças dos Suínos/economia , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/transmissão , Zoonoses/economia , Zoonoses/microbiologia , Zoonoses/prevenção & controle
14.
J Appl Microbiol ; 128(6): 1820-1842, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31999872

RESUMO

AIMS: Staphylococcus aureus is one of the most common pathogens in hospital environment and community. Panton-Valentine leukocidin (PVL) production is clinically associated with skin abscesses, soft tissues infections, bacteraemia and sepsis. This study aimed to investigate the effects of the presence of genes lukF/S-PV coding for PVL, in histological and haematological features during systemic infection, using a Swiss mice experimental model. METHODS AND RESULTS: Experiments were performed using 25 mice distributed into five experimental groups, intravenously inoculated with 50 µl suspensions at density 1·0 × 107  CFU per ml of strains: methicillin-susceptible (MSSA) and pvl-negative strains isolated from nasal colonization; MSSA pvl-positive strains isolated from nasal colonization; methicillin-resistant (MRSA) and pvl-positive strains isolated from peripheral blood of a patient with severe pulmonary infection; and a MRSA pvl-positive strains isolated from a peripheral blood culture of a patient with bacteraemia. Haematological analysis was performed at 24, 48, 72 and 96 h post-infection. Morphoanatomy and histopathological analyses were performed at 96 h post-infection. For all S. aureus strains tested, the capability of intravenous dissemination and survival into mice tissues was demonstrated. Inflammatory processes at different levels were related to the presence of pvl genes, and included alterations in the format, size and colour of the organs. Staphylococcus aureus pvl-positive strains were detected in greater numbers in the organs of the infected animals. CONCLUSIONS: The pvl-positive strains isolated from blood cultures were capable to induce the greatest modifications in both haematological and histopathological profiles, and seemed to aggravate the systemic infections. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings are valuable in characterizing infections caused by S. aureus in humans and murine.


Assuntos
Toxinas Bacterianas/metabolismo , Exotoxinas/metabolismo , Leucocidinas/metabolismo , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Animais , Bacteriemia/microbiologia , Bacteriemia/patologia , Toxinas Bacterianas/genética , Modelos Animais de Doenças , Exotoxinas/genética , Humanos , Leucocidinas/genética , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Staphylococcus aureus Resistente à Meticilina/metabolismo , Camundongos , Staphylococcus aureus/genética , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/metabolismo , Staphylococcus aureus/patogenicidade
15.
BMC Infect Dis ; 20(1): 6, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900118

RESUMO

BACKGROUND: An efficient surface cleaning strategy would first target cleaning to surfaces that make large contributions to the risk of infections. METHODS: In this study, we used data from the literature about methicillin-resistant Staphylococcus aureus (MRSA) and developed an ordinary differential equations based mathematical model to quantify the impact of contact heterogeneity on MRSA transmission in a hypothetical 6-bed intensive care unit (ICU). The susceptible patients are divided into two types, these who are cared by the same nurse as the MRSA infected patient (Type 1) and these who are not (Type 2). RESULTS: The results showed that the mean MRSA concentration on three kinds of susceptible patient nearby surfaces was significantly linearly associated with the hand-touch frequency (p < 0.05). The noncompliance of daily cleaning on patient nearby high-touch surfaces (HTSs) had the most impact on MRSA transmission. If the HTSs were not cleaned, the MRSA exposure to Type 1 and 2 susceptible patients would increase 118.4% (standard deviation (SD): 33.0%) and 115.4% (SD: 30.5%) respectively. The communal surfaces (CSs) had the least impact, if CSs were not cleaned, the MRSA exposure to Type 1 susceptible patient would only increase 1.7% (SD: 1.3). The impact of clinical equipment (CE) differed largely for two types of susceptible patients. If the CE was not cleaned, the exposure to Type 1 patients would only increase 8.4% (SD: 3.0%), while for Type 2 patients, it can increase 70.4% (SD: 25.4%). CONCLUSIONS: This study provided a framework to study the pathogen concentration dynamics on environmental surfaces and quantitatively showed the importance of cleaning patient nearby HTSs on controlling the nosocomial infection transmission via contact route.


Assuntos
Busca de Comunicante/métodos , Unidades de Terapia Intensiva , Staphylococcus aureus Resistente à Meticilina/fisiologia , Modelos Teóricos , Infecções Estafilocócicas/transmissão , Busca de Comunicante/estatística & dados numéricos , Infecção Hospitalar/transmissão , Detergentes/farmacologia , Desinfecção , Feminino , Higiene das Mãos/estatística & dados numéricos , Humanos , Controle de Infecções/métodos , Transmissão de Doença Infecciosa do Paciente para o Profissional/estatística & dados numéricos , Transmissão de Doença Infecciosa do Profissional para o Paciente/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Resistência a Meticilina/fisiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Propriedades de Superfície
16.
J Biomed Sci ; 27(1): 15, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900211

RESUMO

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) ST398 is a livestock associated-bacterium that is most prevalent in Europe. Human-adapted MRSA ST398 was recently reported from China, but there is no data available yet for Taiwan. METHODS: To identify S. aureus ST398 isolates, we examined 6413 S. aureus isolates (5632 MRSA and 781 susceptible strains) that were collected in Taiwan between 1995 and 2017. If isolates could not be typed by pulsed-field gel electrophoresis upon Sma I digestion, we performed further characterization and complete genome sequencing. RESULTS: We identified 18 ST398 S. aureus isolates from 16 subjects (0.28%), including 6 sensitive and 12 resistant strains. Of these, 14 were colonizing isolates, 3 were clinical (infecting) isolates and one isolate was from a pork specimen. All 3 infecting isolates were MSSA strains identified in 2015 from two children with recurrent otitis media or sinusitis. The other 3 MSSA isolates were identified from workers handling pork (2) or pork meat (1) in 2015. The first 5 MRSA colonizing isolates were identified from residents in two nursing homes in 2012. Six MRSA isolates were identified from residents and foreign employees at a nursing home in 2016 and one MRSA from a foreign worker in 2017. Phylogenetic analysis of genome sequences indicated that all 12 local ST398 MRSA strains cluster together, human-adapted and phylogenetically related to a human MRSA strain identified in China in 2002. Two local MSSA isolates could be linked to isolates from livestock. The toxin profiles were similar for the MRSA and MSSA isolates. CONCLUSIONS: Our results demonstrate that S. aureus ST398 was present in Taiwan in 2012 and potentially earlier. Although some isolates could be linked to livestock, most ST398 S. aureus isolates identified in Taiwan, particularly MRSA, represent human-adapted strains. Local transmission of human-adapted MRSA ST398 strains has occurred in nursing homes in Taiwan, possibly after import from China. Further surveillance is needed.


Assuntos
Genoma Bacteriano/genética , Staphylococcus aureus Resistente à Meticilina/genética , Filogenia , Infecções Estafilocócicas/genética , China/epidemiologia , Eletroforese em Gel de Campo Pulsado , Europa (Continente)/epidemiologia , Genótipo , Humanos , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Testes de Sensibilidade Microbiana , Anotação de Sequência Molecular , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Taiwan/epidemiologia , Sequenciamento Completo do Genoma
17.
Eur J Clin Microbiol Infect Dis ; 39(1): 85-92, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31482419

RESUMO

In order to obtain more information on the MRSA population structure in the border region of Afghanistan and Pakistan, we collected and genotyped MRSA causing bloodstream infections from a tertiary care hospital in Peshawar, Pakistan, that serves the local population as well as Afghan immigrants and refugees. Thirty-one MRSA isolates from 30 patients were included and characterized by microarray hybridisation. For 25 patients, serum samples were tested using protein microarrays in order to detect antibodies against staphylococcal virulence factors. The most conspicuous result was the high rate of PVL-positive MRSA. Twenty-two isolates (71%) harboured lukF/S-PV genes. The most common lineage was CC772-MRSA-V/VT (PVL+) to which eleven isolates were assigned. The second most common strain was, surprisingly, CC8-MRSA-[IV+ACME] (PVL+), "USA300" (9 isolates). Two isolates were tst1 positive CC22-MRSA-IV, matching the Middle Eastern "Gaza Epidemic Strain". Another two were PVL-positive CC30-MRSA-IV. The remaining isolates belonged to, possibly locally emerging, CC1, CC5, and CC8 strains with SCC mec IV elements. Twenty-three patient sera were positive for anti-PVL-IgG antibodies. Several questions arise from the present study. It can be assumed that MRSA and high rates of PVL-positive S. aureus/MRSA are a public health issue in the Afghanistan/Pakistan border region. A possible emergence of the "USA300" clone as well as of the CC772 lineage warrants further investigation.


Assuntos
Anticorpos Antibacterianos/sangue , Staphylococcus aureus Resistente à Meticilina/classificação , Sepse/microbiologia , Infecções Estafilocócicas/sangue , Fatores de Virulência/imunologia , Adulto , Afeganistão , Técnicas de Tipagem Bacteriana , Feminino , Genótipo , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Paquistão , Análise Serial de Proteínas , Infecções Estafilocócicas/microbiologia , Fatores de Virulência/genética
18.
J Microbiol Immunol Infect ; 53(2): 292-299, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29907536

RESUMO

PURPOSE: To evaluate the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage in patients with diabetic foot ulcer (DFU) in Taiwan, and to assess the concordance between colonizing and clinical MRSA isolates from the patients. METHOD: A total of 354 nasal specimens were collected from 112 to 242 diabetic patients with and without foot ulcer, respectively. MRSA clinical isolates from DFU wound cultures were collected for comparison. RESULTS: Nasal carriage rate of S. aureus and MRSA was similar between diabetic patients with and without foot ulcer (15.2% vs. 16.9% for S. aureus and 5.4% vs. 1.7% for MRSA). Nasal S. aureus colonization was an independent predictor for wound S. aureus infection (Odds ratio [OR]: 5.33, 95% confidence interval [CI]: 1.61-17.59), so did nasal MRSA colonization (OR: 19.09, 95% CI: 2.12-171.91). The levels of glycated hemoglobin, and the usage with immunosuppressant agent were associated with S. aureus nasal colonization while oral hypoglycemic agent usage a protective factor. Sequence type 59/staphylococcal chromosome cassette mec IV or V, the local endemic community-associated clone, accounted for 42% and 70% of the clinical and colonizing isolates, respectively. Six of 10 patients with paired colonizing and clinical isolates, either MRSA or methicillin-sensitive S. aureus, had a genetically identical strain from a single patient. CONCLUSION: Less than one-fifth of patients with DFU have nasal S. aureus, including MRSA, colonization; however, the colonization is significantly associated with S. aureus diabetic foot infection. Screening for S. aureus colonizing status in DFU patients might have a potential clinical implication.


Assuntos
Portador Sadio/microbiologia , Pé Diabético/complicações , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Nariz/microbiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Animais , Portador Sadio/epidemiologia , Complicações do Diabetes , Diabetes Mellitus , Humanos , Modelos Logísticos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Prevalência , Fatores de Risco , Staphylococcus aureus , Taiwan/epidemiologia
19.
J Dairy Sci ; 103(1): 840-845, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31733844

RESUMO

This study investigated the antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) isolated from cases of subclinical bovine mastitis in China, as well as resistance mechanisms and virulence genes encoding adhesins and toxins. We determined antimicrobial susceptibility using the disk diffusion method, and analyzed resistance, adhesin, and toxin genes using PCR. We confirmed MRSA in 73 of 498 (14.7%) Staph. aureus isolates recovered from subclinical mastitic milk samples. All isolates were positive for mecA. The MRSA isolates showed high resistance to penicillin (100.0%), gentamicin (100.0%), and tetracycline (98.6%). All MRSA isolates harbored resistance genes blaZ (penicillin), aacA/aphD (gentamicin), and tetM (alone or in combination with tetK, tetracycline). Moreover, all isolates carried the adhesin genes fnbpA, clfA, clfB, cna, sdrE, and map/eap, and most carried sdrC (98.6%), sdrD (95.9%), bbp (94.5%), and ebpS (80.8%). The toxin genes seh, hla, and hld were present in all isolates, and most isolates carried sea (71.2%), seg (84.9%), sei (82.2%), lukE-lukD (97.3%), and hlg (72.6%). These findings of high-level resistance to antimicrobials commonly used in dairy cattle should lead to calls for antibiogram analysis before antimicrobial therapy. The high frequency of adhesin and toxin genes in MRSA indicates their potential virulence in bovine mastitis in China.


Assuntos
Mastite Bovina/microbiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/veterinária , Adesinas Bacterianas/genética , Animais , Antibacterianos/farmacologia , Bovinos , China , Feminino , Gentamicinas/farmacologia , Mastite Bovina/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase/veterinária , Infecções Estafilocócicas/microbiologia , Tetraciclina/farmacologia , Virulência/genética
20.
Nat Chem Biol ; 16(2): 143-149, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31768032

RESUMO

Staphylococcus aureus is the leading cause of infections worldwide, and methicillin-resistant strains (MRSA) are emerging. New strategies are urgently needed to overcome this threat. Using a cell-based screen of ~45,000 diverse synthetic compounds, we discovered a potent bioactive, MAC-545496, that reverses ß-lactam resistance in the community-acquired MRSA USA300 strain. MAC-545496 could also serve as an antivirulence agent alone; it attenuates MRSA virulence in Galleria mellonella larvae. MAC-545496 inhibits biofilm formation and abrogates intracellular survival in macrophages. Mechanistic characterization revealed MAC-545496 to be a nanomolar inhibitor of GraR, a regulator that responds to cell-envelope stress and is an important virulence factor and determinant of antibiotic resistance. The small molecule discovered herein is an inhibitor of GraR function. MAC-545496 has value as a research tool to probe the GraXRS regulatory system and as an antibacterial lead series of a mechanism to combat drug-resistant Staphylococcal infections.


Assuntos
Antibacterianos/farmacologia , Ensaios de Triagem em Larga Escala/métodos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Piperidinas/farmacologia , Piridinas/farmacologia , Resistência beta-Lactâmica/efeitos dos fármacos , Animais , Biofilmes/efeitos dos fármacos , Larva/microbiologia , Lepidópteros/microbiologia , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Camundongos , Testes de Sensibilidade Microbiana , Células RAW 264.7 , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Fatores de Virulência/antagonistas & inibidores
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