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1.
J Int Med Res ; 48(8): 300060520933810, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32776805

RESUMO

The sudden outbreak of severe acute respiratory syndrome coronavirus 2 pneumonia posed a significant challenge to medical professionals because treatment of critically ill patients requires the efforts of a multidisciplinary team. To highlight this principle, we examined acute kidney injury (AKI) in IgA-dominant infection-associated glomerulonephritis (GN) and menstrual toxic shock syndrome (mTSS). Both GN and mTSS are rare diseases caused by staphylococcal infection, and renal function is frequently impaired. The resulting AKIs are disparate pathological entities driven by distinct immune mechanisms. We begin by describing the case of a diabetic man with pyopneumothorax following methicillin-resistant Staphylococcus aureus (MRSA). He had endocapillary proliferative GN with in situ IgA-dominant immune-complex formation in the mesangium accompanied by complement C3 deposition in the glomerular capillary wall. By contrast, acute tubular necrosis was observed in a case of mTSS; the patient's immune response was stimulated differently by MRSA enterotoxin and exotoxin resulting in aberrant IgA deposition, complement activation, and insufficient antibody production. As a multidisciplinary communication covering the fields of nephrology, immunology, and pathology, this report may help clinicians to understand these distinct renal lesions and make optimal therapeutic decisions expeditiously.


Assuntos
Lesão Renal Aguda/patologia , Glomerulonefrite por IGA/patologia , Imunoglobulina A/imunologia , Distúrbios Menstruais/patologia , Choque Séptico/patologia , Infecções Estafilocócicas/patologia , Lesão Renal Aguda/microbiologia , Adolescente , Betacoronavirus , Ativação do Complemento/imunologia , Infecções por Coronavirus/patologia , Enterotoxinas/metabolismo , Feminino , Glomerulonefrite por IGA/microbiologia , Humanos , Rim/patologia , Masculino , Distúrbios Menstruais/microbiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Pneumotórax/microbiologia , Pneumotórax/patologia , Choque Séptico/microbiologia
2.
BMC Infect Dis ; 20(1): 512, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32677896

RESUMO

BACKGROUND: The aims of this study were to identify the predictive factors for microbiological diagnosis through disco-vertebral biopsy (DVB) in patients with pyogenic vertebral osteomyelitis (PVO) and negative blood cultures, and compare the performance of DVB under fluoroscopic versus scanographic guidance. METHODS: We performed a cohort study comparing positive and negative DVB among patients with PVO. All cases of PVO undergoing a DVB for microbiological diagnosis in our center were retrospectively reviewed. Infections due to Mycobacterium tuberculosis, infections on foreign device, and non-septic diseases were excluded. Anamnestic, clinical, biological, microbiological, as well as radiological data were collected from medical charts thanks to a standardized data set. RESULTS: A total of 111 patients were screened; 88 patients were included. Microbiological cultures were positive in 53/88 (60.2%) patients. A thickening of the paravertebral tissue ≥10 mm on magnetic resonance imaging (MRI) in axial MR scans was a predictive factor of DVB microbiological positivity (52.4% vs. 13.3%; p = 0.006; OR = 5.4). Overall, 51 DVB were performed under fluoroscopic guidance and 37 under scanographic guidance. Considering lumbar DVB, 25/36 (69.4%) of cases yielded positive results under fluoroscopic guidance versus 5/15 (33.3%) under scanographic guidance (p = 0.02; OR = 4.4). No adverse event linked to DVB was notified. CONCLUSION: Every patient with PVO and negative blood cultures should undergo a DVB. A thickening of the paravertebral tissue ≥10 mm on MRI is associated with a higher rate of positive DVB culture. A lumbar DVB under fluoroscopic guidance is more sensitive than under scanographic guidance to identify the micro-organism involved.


Assuntos
Disco Intervertebral/patologia , Vértebras Lombares/patologia , Osteomielite/diagnóstico , Doenças da Coluna Vertebral/diagnóstico , Infecções Estafilocócicas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Abscesso Epidural/diagnóstico , Abscesso Epidural/patologia , Feminino , Fluoroscopia/métodos , Humanos , Biópsia Guiada por Imagem/métodos , Disco Intervertebral/microbiologia , Vértebras Lombares/microbiologia , Masculino , Pessoa de Meia-Idade , Osteomielite/microbiologia , Osteomielite/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Doenças da Coluna Vertebral/microbiologia , Doenças da Coluna Vertebral/patologia , Infecções Estafilocócicas/patologia , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
3.
PLoS Genet ; 16(7): e1008779, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32730248

RESUMO

Staphylococcus aureus is an opportunistic pathogen that can grow in a wide array of conditions: on abiotic surfaces, on the skin, in the nose, in planktonic or biofilm forms and can cause many type of infections. Consequently, S. aureus must be able to adapt rapidly to these changing growth conditions, an ability largely driven at the posttranscriptional level. RNA helicases of the DEAD-box family play an important part in this process. In particular, CshA, which is part of the degradosome, is required for the rapid turnover of certain mRNAs and its deletion results in cold-sensitivity. To understand the molecular basis of this phenotype, we conducted a large genetic screen isolating 82 independent suppressors of cold growth. Full genome sequencing revealed the fatty acid synthesis pathway affected in many suppressor strains. Consistent with that result, sublethal doses of triclosan, a FASII inhibitor, can partially restore growth of a cshA mutant in the cold. Overexpression of the genes involved in branched-chain fatty acid synthesis was also able to suppress the cold-sensitivity. Using gas chromatography analysis of fatty acids, we observed an imbalance of straight and branched-chain fatty acids in the cshA mutant, compared to the wild-type. This imbalance is compensated in the suppressor strains. Thus, we reveal for the first time that the cold sensitive growth phenotype of a DEAD-box mutant can be explained, at least partially, by an improper membrane composition. The defect correlates with an accumulation of the pyruvate dehydrogenase complex mRNA, which is inefficiently degraded in absence of CshA. We propose that the resulting accumulation of acetyl-CoA fuels straight-chained fatty acid production at the expense of the branched ones. Strikingly, addition of acetate into the medium mimics the cshA deletion phenotype, resulting in cold sensitivity suppressed by the mutations found in our genetic screen or by sublethal doses of triclosan.


Assuntos
RNA Helicases DEAD-box/genética , Ácidos Graxos/metabolismo , Infecções Estafilocócicas/genética , Staphylococcus aureus/genética , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Ácidos Graxos/genética , Regulação Bacteriana da Expressão Gênica/genética , Humanos , Proteínas de Membrana/genética , RNA Mensageiro/genética , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/patogenicidade
4.
PLoS Pathog ; 16(6): e1008511, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32555671

RESUMO

The clinical importance of microbiomes to the chronicity of wounds is widely appreciated, yet little is understood about patient-specific processes shaping wound microbiome composition. Here, a two-cohort microbiome-genome wide association study is presented through which patient genomic loci associated with chronic wound microbiome diversity were identified. Further investigation revealed that alternative TLN2 and ZNF521 genotypes explained significant inter-patient variation in relative abundance of two key pathogens, Pseudomonas aeruginosa and Staphylococcus epidermidis. Wound diversity was lowest in Pseudomonas aeruginosa infected wounds, and decreasing wound diversity had a significant negative linear relationship with healing rate. In addition to microbiome characteristics, age, diabetic status, and genetic ancestry all significantly influenced healing. Using structural equation modeling to identify common variance among SNPs, six loci were sufficient to explain 53% of variation in wound microbiome diversity, which was a 10% increase over traditional multiple regression. Focusing on TLN2, genotype at rs8031916 explained expression differences of alternative transcripts that differ in inclusion of important focal adhesion binding domains. Such differences are hypothesized to relate to wound microbiomes and healing through effects on bacterial exploitation of focal adhesions and/or cellular migration. Related, other associated loci were functionally enriched, often with roles in cytoskeletal dynamics. This study, being the first to identify patient genetic determinants for wound microbiomes and healing, implicates genetic variation determining cellular adhesion phenotypes as important drivers of infection type. The identification of predictive biomarkers for chronic wound microbiomes may serve as risk factors and guide treatment by informing patient-specific tendencies of infection.


Assuntos
Microbiota , Polimorfismo de Nucleotídeo Único , Infecções por Pseudomonas , Pseudomonas aeruginosa , Infecções Estafilocócicas , Staphylococcus epidermidis , Cicatrização/genética , Infecção dos Ferimentos , Animais , Doença Crônica , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Camundongos , Infecções por Pseudomonas/genética , Infecções por Pseudomonas/metabolismo , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/patologia , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Talina/genética , Talina/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Infecção dos Ferimentos/genética , Infecção dos Ferimentos/metabolismo , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
5.
PLoS One ; 15(5): e0231168, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32365127

RESUMO

Staphylococcus aureus is one of the most important pathogens causing mastitis in dairy cows. The objective of this study was to establish a rat model of mastitis induced by S. aureus infection and to explore changes in the proteomes of mammary tissue in different udder states, providing a better understanding of the host immune response to S. aureus mastitis. On day 3 post-partum, 6 rats were randomly divided into two groups (n = 3), with either 100 µL of PBS (blank group) or a S. aureus suspension containing 2×107 CFU·mL-1 (challenge group) infused into the mammary gland duct. After 24 h of infection, the rats were sacrificed, and mammary gland tissue was collected. Tandem mass tag (TMT)-based technology was applied to compare the proteomes of healthy and mastitic mammary tissues. Compared with the control group, the challenge group had 555 proteins with significant differences in expression, of which 428 were significantly upregulated (FC>1.2 and p<0.05) and 127 were downregulated (FC>0.83 and p<0.05 or p<0.01). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that upregulated differentially significant expressed proteins (DSEPs) were associated with mainly immune responses, including integrin alpha M, inter-α-trypsin inhibitor heavy chain 4, and alpha-2-macroglobulin. This study is the first in which a rat model of S. aureus-induced mastitis was used to explore the proteins related to mastitis in dairy cows by TMT technology, providing a model for replication of dairy cow S. aureus-induced mastitis experiments.


Assuntos
Glândulas Mamárias Animais/metabolismo , Mastite/metabolismo , Proteoma/análise , Infecções Estafilocócicas/metabolismo , Staphylococcus aureus/fisiologia , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Feminino , Glândulas Mamárias Animais/microbiologia , Glândulas Mamárias Animais/patologia , Mastite/microbiologia , Mastite/patologia , Gravidez , Proteoma/metabolismo , Proteômica/métodos , Ratos , Ratos Sprague-Dawley , Infecções Estafilocócicas/patologia , Espectrometria de Massas em Tandem
6.
Medicine (Baltimore) ; 99(15): e19746, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282735

RESUMO

RATIONALE: Toxic shock syndrome (TSS) typically is an acute onset multi-organ infection caused by TSS toxin-1 producing Staphylococcus aureus. Herein we describe a highly unusual case report. PATIENT CONCERNS: A male patient self-referred to the University of Minnesota Hospital with a chronic history of S aureus infection with accompanying fever, hypotension, and nonhealing, football-sized lesion on his leg. DIAGNOSIS: An unusual case presentation of TSS/hyperimmunoglobulin E syndrome is described. The patient had a leg wound from which TSS toxin-1 S aureus was isolated. The patient exhibited characteristic skewing of T cells to those with variable region, ß-chain T cell receptor-2. Other patients have been seen with related presentations. INTERVENTIONS: The following therapeutic regimen was instituted: vigorous antibacterial scrubs several times daily plus intravenous Ancef 3 days each month; intravenous infusions of immunoglobulin G infusions (28 gm) every 3 weeks; and weekly subcutaneous injections of recombinant granulocyte colony-stimulating factor. OUTCOME: Improvement was obvious within 3 months: no further cellulitic episodes occurred; the patient regained 95 pounds in 9 months; blanching and cyanosis of fingers disappeared within 3 months as did intractable pain although mild hypesthesias continued for 2 years; erythroderma resolved, and repeat skin biopsies performed after 2 years no longer demonstrated T cell receptor skewing. Although IgE levels have not completely returned to normal, the patient remains in excellent health. LESSONS: We propose that staphylococcal TSST-1 was responsible for the serious problems suffered by this patient as suggested by the following features: rapid onset of chronic, life-threatening, disorder that began with an episode of staphylococcal sepsis; the extraordinary elevation of IgE levels in this previously non-atopic individual; the acquired severe granulocyte chemotactic defect that accompanied this hyperimmunoglobulinemia ("Job Syndrome") with its accompanying wound-healing defect; and the striking diffuse erythroderma, including palmar erythema ("Red Man Syndrome") with hypotension and fever that also characterizes TSS.


Assuntos
Síndrome de Job/microbiologia , Choque Séptico/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Administração Intravenosa , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Cefazolina/administração & dosagem , Cefazolina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Imunoglobulina G/administração & dosagem , Imunoglobulina G/uso terapêutico , Infusões Intravenosas , Injeções Subcutâneas , Síndrome de Job/diagnóstico , Síndrome de Job/etiologia , Perna (Membro)/patologia , Masculino , Pessoa de Meia-Idade , Choque Séptico/diagnóstico , Choque Séptico/etiologia , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/patologia , Resultado do Tratamento , Ferimentos e Lesões/microbiologia
7.
PLoS Pathog ; 16(3): e1008354, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32142554

RESUMO

Biofilm-associated prosthetic joint infections (PJIs) cause significant morbidity due to their recalcitrance to immune-mediated clearance and antibiotics, with Staphylococcus aureus (S. aureus) among the most prevalent pathogens. We previously demonstrated that S. aureus biofilm-associated monocytes are polarized to an anti-inflammatory phenotype and the adoptive transfer of pro-inflammatory macrophages attenuated biofilm burden, highlighting the critical role of monocyte/macrophage inflammatory status in dictating biofilm persistence. The inflammatory properties of leukocytes are linked to their metabolic state, and here we demonstrate that biofilm-associated monocytes exhibit a metabolic bias favoring oxidative phosphorylation (OxPhos) and less aerobic glycolysis to facilitate their anti-inflammatory activity and biofilm persistence. To shift monocyte metabolism in vivo and reprogram cells to a pro-inflammatory state, a nanoparticle approach was utilized to deliver the OxPhos inhibitor oligomycin to monocytes. Using a mouse model of S. aureus PJI, oligomycin nanoparticles were preferentially internalized by monocytes, which significantly reduced S. aureus biofilm burden by altering metabolism and promoting the pro-inflammatory properties of infiltrating monocytes as revealed by metabolomics and RT-qPCR, respectively. Injection of oligomycin alone had no effect on monocyte metabolism or biofilm burden, establishing that intracellular delivery of oligomycin is required to reprogram monocyte metabolic activity and that oligomycin lacks antibacterial activity against S. aureus biofilms. Remarkably, monocyte metabolic reprogramming with oligomycin nanoparticles was effective at clearing established biofilms in combination with systemic antibiotics. These findings suggest that metabolic reprogramming of biofilm-associated monocytes may represent a novel therapeutic approach for PJI.


Assuntos
Biofilmes/efeitos dos fármacos , Reprogramação Celular/efeitos dos fármacos , Implantes Experimentais/microbiologia , Monócitos/metabolismo , Oligomicinas/farmacologia , Infecções Estafilocócicas/metabolismo , Staphylococcus aureus/fisiologia , Animais , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Monócitos/patologia , Fosforilação Oxidativa/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/patologia
8.
Am J Pathol ; 190(6): 1151-1163, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32194053

RESUMO

Osteomyelitis is an inflammation of the bone and bone marrow that is most commonly caused by a Staphylococcus aureus infection. Much of our understanding of the underlying pathophysiology of osteomyelitis, from the perspective of both host and pathogen, has been revised in recent years, with notable discoveries including the role played by osteocytes in the recruitment of immune cells, the invasion and persistence of S. aureus in submicron channels of cortical bone, and the diagnostic role of polymorphonuclear cells in implant-associated osteomyelitis. Advanced in vitro cell culture models, such as ex vivo culture models or organoids, have also been developed over the past decade, and have become widespread in many fields, including infectious diseases. These models better mimic the in vivo environment, allow the use of human cells, and can reduce our reliance on animals in osteomyelitis research. In this review, we provide an overview of the main pathologic concepts in osteomyelitis, with a focus on the new discoveries in recent years. Furthermore, we outline the value of modern in vitro cell culture techniques, with a focus on their current application to infectious diseases and osteomyelitis in particular.


Assuntos
Osteomielite/imunologia , Osteomielite/patologia , Infecções Estafilocócicas/patologia , Animais , Modelos Animais de Doenças , Humanos , Osteócitos/patologia , Projetos de Pesquisa , Infecções Estafilocócicas/imunologia , Staphylococcus aureus
9.
PLoS One ; 15(2): e0227823, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32012172

RESUMO

Staphylococcus epidermidis has emerged as the leading agent causing neonatal late-onset sepsis in preterm neonates; although the severity of the episodes caused by this species is often underestimated, it might exert relevant short- and long-term detrimental effects on neonatal outcomes. In this context, the objective of this study was to characterize a collection of S. epidermidis strains obtained from meconium and feces of preterm infants, and to assess the potential role of the enteral feeding tubes as potential reservoirs for this microorganism. A total of 26 preterm infants were enrolled in the study. Meconium and fecal samples were collected weekly during their first month of life (n = 92). Feeding samples were collected after their pass through the enteral feeding tubes (n = 84). S. epidermidis was present in the fecal samples of all the infants in, at least, one sampling time at concentrations ranging from 6.5 to 7.8 log10 CFU/g. Initially, 344 isolates were obtained and pulsed-field gel electrophoresis (PFGE) profiling allowed the reduction of the collection to 101 strains. Among them, multilocus sequence typing (MLST) profiling showed the presence of 32 different sequence types (ST). Globally, most of the STs to hospital-adapted high-risk clones and belonged to clonal complexes (CC) associated to the hospital environment, such as CC2. The virulence gene most commonly detected among the strains was altE. High resistance rates to macrolides and aminoglycosides were detected and 64% of the strains harboured the mecA gene, which was codified in SCCmec types. Our results indicates the existence of a complex and genetically diverse S. epidermidis population in the NICU environment. A better knowledge of S. epidermidis strains may help to devise strategies to avoid their conversion from symbiont to pathobiont microorganisms in the NICUs.


Assuntos
Epidemiologia Molecular , Sepse Neonatal/genética , Infecções Estafilocócicas/genética , Staphylococcus epidermidis/genética , Antibacterianos/uso terapêutico , Eletroforese em Gel de Campo Pulsado , Nutrição Enteral/efeitos adversos , Fezes/microbiologia , Genótipo , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Testes de Sensibilidade Microbiana , Sepse Neonatal/microbiologia , Sepse Neonatal/patologia , Sepse Neonatal/prevenção & controle , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus epidermidis/isolamento & purificação , Staphylococcus epidermidis/patogenicidade
10.
World Neurosurg ; 137: 281-285, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32081825

RESUMO

BACKGROUND: Pituitary abscesses within pre-existing pituitary conditions, such as craniopharyngioma, pituitary adenoma, or Rathke cleft cyst, are quite rare. A case of pituitary abscess secondary to adenoma is presented, and the literature is reviewed. CASE DESCRIPTION: An 11-year-old boy presented with a 3-day history of sudden-onset headache and visual loss. Magnetic resonance imaging demonstrated a sellar region lesion with intralesional hemorrhage. Preoperative diagnosis was pituitary adenoma with apoplexy. An endoscopic transnasal transsphenoidal approach was used for emergent total tumor resection. Pathology confirmed the diagnosis of pituitary adenoma with apoplexy and inflammation, and microbiologic examination was positive for Staphylococcus aureus. CONCLUSIONS: Secondary pituitary abscess is a rare entity, and preoperative diagnosis is challenging. The treatment strategy includes prompt surgical resection and drainage of the abscess, followed by prolonged antibiotic therapy.


Assuntos
Adenoma/complicações , Abscesso Encefálico/etiologia , Procedimentos Neurocirúrgicos , Apoplexia Hipofisária/complicações , Neoplasias Hipofisárias/complicações , Sinusite Esfenoidal/complicações , Infecções Estafilocócicas/etiologia , Doença Aguda , Adenoma/diagnóstico por imagem , Adenoma/patologia , Adenoma/cirurgia , Antibacterianos/uso terapêutico , Abscesso Encefálico/patologia , Abscesso Encefálico/terapia , Criança , Cefaleia/etiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Apoplexia Hipofisária/diagnóstico por imagem , Apoplexia Hipofisária/patologia , Apoplexia Hipofisária/cirurgia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Sinusite Esfenoidal/diagnóstico por imagem , Sinusite Esfenoidal/terapia , Infecções Estafilocócicas/patologia , Infecções Estafilocócicas/terapia , Staphylococcus aureus , Transtornos da Visão/etiologia
11.
PLoS One ; 15(1): e0225077, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31951610

RESUMO

BACKGROUND: The data on infective endocarditis after transcatheter aortic valve implantation (TAVI) is scarce and limited to case reports and case series in the literature. It is the need of the hour to analyze the available data on post-TAVI infective endocarditis from the available literature. The objectives of this systematic review were to evaluate the incidence of infective endocarditis after transcatheter aortic valve implantation, its microbiological profile and clinical outcomes. It will help us to improve the antibiotic prophylaxis strategies and treatment options for infective endocarditis in the context of TAVI. METHODS: EMBASE, Medline and the CENTRAL trials registry of the Cochrane Collaboration were searched for articles on infective endocarditis in post-TAVI patients till October 2018. Eleven articles were included in the systematic review. The outcomes assessed werethe incidence of infective endocarditis, its microbiological profile andclinical outcomes including major adverse cardiac event (MACE), net adverse clinical event (NACE), surgical intervention and valve-in-valve procedure. RESULTS: The incidence of infective endocarditis varied from 0%-14.3% in the included studies, the mean was3.25%. The average duration of follow-up was 474 days (1.3 years). Enterococci were the most common causative organism isolated from 25.9% of cases followed by Staphylococcus aureus (16.1%) and coagulase-negative Staphylococcus species (14.7%). The mean in-hospital mortality and mortality at follow-up was 29.5% and 29.9%, respectively. The cumulative incidence of heart failure, stroke and major bleeding were 37.1%, 5.3% and 11.3%,respectively. Only a single study by Martinez-Selles et al. reported arrhythmias in 20% cases. The septic shock occurred in 10% and 27.7% post-TAVI infective endocarditis patients according to 2 studies. The surgical intervention and valve-in-valve procedure were reported in 11.4% and 6.4% cases, respectively. CONCLUSION: The incidence of post-TAVI infective endocarditis is low being 3.25% but it is associated with high mortality and complications. The most common complication is heart failure with a cumulative incidence of 37.1%. Enterococciare the most common causative organism isolated from 25.9% of cases followed by Staphylococcus aureus in 16.1% of cases. Appropriate measures should be taken to prevent infective endocarditis in post-TAVI patients including adequate antibiotics prophylaxis directed specifically against these organisms. STUDY REGISTRATION: PROSPERO registration number CRD42018115943.


Assuntos
Endocardite Bacteriana/microbiologia , Endocardite/microbiologia , Infecções Relacionadas à Prótese/microbiologia , Infecções Estafilocócicas/microbiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibioticoprofilaxia/métodos , Endocardite/tratamento farmacológico , Endocardite/epidemiologia , Endocardite/patologia , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/epidemiologia , Endocardite Bacteriana/patologia , Enterococcus/efeitos dos fármacos , Enterococcus/patogenicidade , Feminino , Próteses Valvulares Cardíacas/microbiologia , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/patologia , Fatores de Risco , Caracteres Sexuais , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/patogenicidade , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
12.
Immunology ; 159(4): 404-412, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31909831

RESUMO

Dendritic cells (DCs) are potent immune cells that control innate and adaptive immune responses. Previous studies have shown that the DCs are required for protection against Staphylococcus aureus infection. However, the role of conventional DC (cDC) subsets during S. aureus infection in vivo has not been well investigated. In this study, we examined the function of spleen DC subsets in the activation of immunity against S. aureus infection. C57BL/6 mice were infected intravenously with S. aureus and DC and T-cell activation were analyzed in vivo. We found that the spleen CD8α- cDCs phagocytosed S. aureus more efficiently than type-1 conventional DCs (cDC1s) did. Moreover, the CD8α- cDCs contributed to the production of pro-inflammatory cytokines in response to S. aureus infection, whereas the cDC1s did not. In addition, infection with S. aureus promoted an increase in the number of Vß T cells. The CD4+ and CD8+ Vß T cells up-regulated the production of interferon-γ (IFN-γ) and interleukin-17 (IL-17) in response to S. aureus infection. Importantly, the induction of IFN-γ and IL-17 production in CD4+ and CD8+ Vß T cells was mediated by S. aureus-stimulated CD8α- cDCs, whereas cDC1s failed to promote IFN-γ and IL-17 production in the cells. Therefore, these data suggested that the spleen CD8α- cDCs are the main DC subsets for induction of S. aureus superantigen-specific immunity.


Assuntos
Antígenos CD8/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/microbiologia , Linfócitos T CD4-Positivos/patologia , Antígenos CD8/deficiência , Antígenos CD8/genética , Linfócitos T CD8-Positivos/microbiologia , Linfócitos T CD8-Positivos/patologia , Linhagem da Célula/imunologia , Células Dendríticas/microbiologia , Expressão Gênica , Interações Hospedeiro-Patógeno/imunologia , Imunidade Celular , Interferon gama/genética , Interferon gama/imunologia , Interleucina-17/genética , Interleucina-17/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Fagocitose , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Baço/imunologia , Baço/microbiologia , Baço/patologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/patogenicidade
13.
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
14.
Biomater Sci ; 8(1): 391-404, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31728464

RESUMO

Prevention of bacterial infection and promotion of osseointegration are two important issues for titanium (Ti) implants in medical research. In addition, after a biofilm is formed on the surface of implants, the immune system and antibiotic therapy may fail. In this work, bio-functionalized titanium dioxide (TiO2)/molybdenum disulfide (MoS2)/polydopamine (PDA)/arginine-glycine-aspartic acid (RGD) nanorod arrays (NAs) are prepared on Ti implants to not only kill bacteria noninvasively upon co-irradiation of 660 nm visible light (VL) and 808 nm near infrared (NIR) light, but also promote the osteogenic activity simultaneously. Dual light irradiation triggers the TiO2/MoS2 NA to generate hyperthermia and reactive oxygen species (ROS) in 10 min. The synergistic effects of the generated hyperthermia and ROS increase the bacterial membrane permeability and bacteria are killed rapidly and efficiently in vitro and in vivo. The biofilm is also eradicated and RGD on the nanorods improves cell adhesion, proliferation, and osteogenic differentiation. The strategy described here for the design of bio-functionalized coatings on Ti implants has great clinical potential in orthopedics, dentistry, and other medical fields.


Assuntos
Antibacterianos/química , Materiais Revestidos Biocompatíveis/química , Luz , Nanotubos/química , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/uso terapêutico , Dissulfetos/química , Glutationa/química , Hipertermia Induzida , Indóis/química , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos , Molibdênio/química , Oligopeptídeos/química , Osteogênese/efeitos dos fármacos , Polímeros/química , Espécies Reativas de Oxigênio/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/patologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Titânio/química
15.
Cell Rep ; 29(12): 3974-3982.e4, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31851927

RESUMO

The essentiality of fatty acid synthesis (FASII) products in the human pathogen Staphylococcus aureus is the underlying rationale for FASII-targeted antimicrobial drug design. Reports of anti-FASII efficacy in animals support this choice. However, restricted test conditions used previously led us to investigate this postulate in a broader, host-relevant context. We report that S. aureus rapidly adapts to FASII antibiotics without FASII mutations when exposed to host environments. FASII antibiotic administration upon signs of infection, rather than just after inoculation as commonly practiced, fails to eliminate S. aureus in a septicemia model. In vitro, serum lowers S. aureus membrane stress, leading to a greater retention of the substrates required for environmental fatty acid (eFA) utilization: eFAs and the acyl carrier protein. In this condition, eFA occupies both phospholipid positions, regardless of anti-FASII selection. Our results identify S. aureus membrane plasticity in host environments as a main limitation for using FASII antibiotics in monotherapeutic treatments.


Assuntos
Adaptação Fisiológica , Antibacterianos/farmacologia , Ácidos Graxos/metabolismo , Interações Hospedeiro-Patógeno , Sepse/patologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Farmacorresistência Bacteriana , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Sepse/tratamento farmacológico , Sepse/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia
16.
Molecules ; 24(21)2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31731408

RESUMO

Staphylococcus aureus and Staphylococcus epidermidis are considered two of the most important pathogens, and their biofilms frequently cause device-associated infections. Microbial biosurfactants recently emerged as a new generation of anti-adhesive and anti-biofilm agents for coating implantable devices to preserve biocompatibility. In this study, R89 biosurfactant (R89BS) was evaluated as an anti-biofilm coating on medical-grade silicone. R89BS is composed of homologues of the mono- (75%) and di-rhamnolipid (25%) families, as evidenced by mass spectrometry analysis. The antimicrobial activity against Staphylococcus spp. planktonic and sessile cells was evaluated by microdilution and metabolic activity assays. R89BS inhibited S. aureus and S. epidermidis growth with minimal inhibitory concentrations (MIC99) of 0.06 and 0.12 mg/mL, respectively and dispersed their pre-formed biofilms up to 93%. Silicone elastomeric discs (SEDs) coated by R89BS simple adsorption significantly counteracted Staphylococcus spp. biofilm formation, in terms of both built-up biomass (up to 60% inhibition at 72 h) and cell metabolic activity (up to 68% inhibition at 72 h). SEM analysis revealed significant inhibition of the amount of biofilm-covered surface. No cytotoxic effect on eukaryotic cells was detected at concentrations up to 0.2 mg/mL. R89BS-coated SEDs satisfy biocompatibility requirements for leaching products. Results indicate that rhamnolipid coatings are effective anti-biofilm treatments and represent a promising strategy for the prevention of infection associated with implantable devices.


Assuntos
Biofilmes/efeitos dos fármacos , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Tensoativos/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Próteses e Implantes/efeitos adversos , Próteses e Implantes/microbiologia , Infecções Relacionadas à Prótese/microbiologia , Elastômeros de Silicone/química , Elastômeros de Silicone/farmacologia , Silicones/química , Silicones/farmacologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Staphylococcus epidermidis/patogenicidade , Tensoativos/química
17.
Int J Mol Sci ; 20(22)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31703398

RESUMO

Neutrophils are key to host defence, and impaired neutrophil function predisposes to infection with an array of pathogens, with Staphylococcus aureus a common and sometimes life-threatening problem in this setting. Both infiltrating immune cells and replicating bacteria consume oxygen, contributing to the profound tissue hypoxia that characterises sites of infection. Hypoxia in turn has a dramatic effect on both neutrophil bactericidal function and the properties of S. aureus, including the production of virulence factors. Hypoxia thereby shapes the host-pathogen interaction and the progression of infection, for example promoting intracellular bacterial persistence, enabling local tissue destruction with the formation of an encaging abscess capsule, and facilitating the establishment and propagation of bacterial biofilms which block the access of host immune cells. Elucidating the molecular mechanisms underlying host-pathogen interactions in the setting of hypoxia will enable better understanding of persistent and recalcitrant infections due to S. aureus and may uncover novel therapeutic targets and strategies.


Assuntos
Biofilmes/crescimento & desenvolvimento , Interações Hospedeiro-Patógeno , Neutrófilos , Infecções Estafilocócicas/metabolismo , Staphylococcus aureus/fisiologia , Fatores de Virulência/metabolismo , Animais , Hipóxia Celular , Humanos , Neutrófilos/metabolismo , Neutrófilos/microbiologia , Neutrófilos/patologia , Infecções Estafilocócicas/patologia , Infecções Estafilocócicas/terapia
18.
PLoS One ; 14(11): e0220421, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31756187

RESUMO

Osteomyelitis, or bone infection, is often induced by antibiotic resistant Staphylococcus aureus strains of bacteria. Although debridement and long-term administration of antibiotics are the gold standard for osteomyelitis treatment, the increase in prevalence of antibiotic resistant bacterial strains limits the ability of clinicians to effectively treat infection. Bacteriophages (phages), viruses that in a lytic state can effectively kill bacteria, have gained recent attention for their high specificity, abundance in nature, and minimal risk of host toxicity. Previously, we have shown that CRISPR-Cas9 genomic editing techniques could be utilized to expand temperate bacteriophage host range and enhance bactericidal activity through modification of the tail fiber protein. In a dermal infection study, these CRISPR-Cas9 phages reduced bacterial load relative to unmodified phage. Thus we hypothesized this temperate bacteriophage, equipped with the CRISPR-Cas9 bactericidal machinery, would be effective at mitigating infection from a biofilm forming S. aureus strain in vitro and in vivo. In vitro, qualitative fluorescent imaging demonstrated superiority of phage to conventional vancomycin and fosfomycin antibiotics against S. aureus biofilm. Quantitative antibiofilm effects increased over time, at least partially, for all fosfomycin, phage, and fosfomycin-phage (dual) therapeutics delivered via alginate hydrogel. We developed an in vivo rat model of osteomyelitis and soft tissue infection that was reproducible and challenging and enabled longitudinal monitoring of infection progression. Using this model, phage (with and without fosfomycin) delivered via alginate hydrogel were successful in reducing soft tissue infection but not bone infection, based on bacteriological, histological, and scanning electron microscopy analyses. Notably, the efficacy of phage at mitigating soft tissue infection was equal to that of high dose fosfomycin. Future research may utilize this model as a platform for evaluation of therapeutic type and dose, and alternate delivery vehicles for osteomyelitis mitigation.


Assuntos
Bacteriófagos , Osteomielite/terapia , Infecções dos Tecidos Moles/terapia , Infecções Estafilocócicas/terapia , Staphylococcus aureus , Animais , Antibacterianos/farmacologia , Bacteriófagos/genética , Biofilmes , Sistemas CRISPR-Cas , Modelos Animais de Doenças , Feminino , Fosfomicina/farmacologia , Edição de Genes , Estudos Longitudinais , Osteomielite/microbiologia , Osteomielite/patologia , Ratos , Ratos Sprague-Dawley , Infecções dos Tecidos Moles/microbiologia , Infecções dos Tecidos Moles/patologia , Infecções Estafilocócicas/patologia , Vancomicina/farmacologia
19.
Bull Exp Biol Med ; 167(6): 784-786, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31656000

RESUMO

Antibacterial activity of powdered preparations based on copper and silver nanoparticles was compared with activity of the reference preparation Baneocin on the model of local staphylococcal infection in white rats. The developed preparations exhibited pronounced antibacterial activity against methicillin-resistant S. epidermidis strains in vivo significantly (p<0.001) exceeding that of Baneocin, reduced microbial contamination of the wound on day 5 of study by 2 lg and more in comparison with bacterial load before treatment, and provided effective decontamination of the wound within 7-10 days.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus epidermidis/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Administração Tópica , Animais , Animais não Endogâmicos , Antibacterianos/administração & dosagem , Antibacterianos/química , Anti-Infecciosos Locais/química , Cobre/administração & dosagem , Cobre/química , Humanos , Nanopartículas Metálicas/química , Resistência a Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Ratos , Prata/administração & dosagem , Prata/química , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/patologia , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
20.
Proc Natl Acad Sci U S A ; 116(44): 21980-21982, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31611408

RESUMO

Siderophores, iron-scavenging small molecules, are fundamental to bacterial nutrient metal acquisition and enable pathogens to overcome challenges imposed by nutritional immunity. Multimodal imaging mass spectrometry allows visualization of host-pathogen iron competition, by mapping siderophores within infected tissue. We have observed heterogeneous distributions of Staphylococcus aureus siderophores across infectious foci, challenging the paradigm that the vertebrate host is a uniformly iron-depleted environment to invading microbes.


Assuntos
Sideróforos/análise , Staphylococcus aureus/patogenicidade , Abscesso/microbiologia , Animais , Citratos/análise , Interações Hospedeiro-Patógeno , Ferro/metabolismo , Camundongos , Ornitina/análogos & derivados , Ornitina/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia
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