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1.
Medicine (Baltimore) ; 98(38): e17185, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567961

RESUMO

Infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus (PVL-SA) mostly present as recurrent skin abscesses and furunculosis. However, life-threatening infections (eg, necrotizing pneumonia, necrotizing fasciitis, and osteomyelitis) caused by PVL-SA have also been reported.We assessed the clinical phenotype, frequency, clinical implications (surgery, length of treatment in hospitals/intensive care units, and antibiotic treatments), and potential preventability of severe PVL-SA infections in children.Total, 75 children treated for PVL-SA infections in our in- and outpatient units from 2012 to 2017 were included in this retrospective study.Ten out of 75 children contracted severe infections (PVL-methicillin resistant S aureus n = 4) including necrotizing pneumonia (n = 4), necrotizing fasciitis (n = 2), pyomyositis (n = 2; including 1 patient who also had pneumonia), mastoiditis with cerebellitis (n = 1), preorbital cellulitis (n = 1), and recurrent deep furunculosis in an immunosuppressed patient (n = 1). Specific complications of PVL-SA infections were venous thrombosis (n = 2), sepsis (n = 5), respiratory failure (n = 5), and acute respiratory distress syndrome (n = 3). The median duration of hospital stay was 14 days (range 5-52 days). In 6 out of 10 patients a history suggestive for PVL-SA colonization in the patient or close family members before hospital admission was identified.PVL-SA causes severe to life-threatening infections requiring lengthy treatments in hospital in a substantial percentage of symptomatic PVL-SA colonized children. More than 50% of severe infections might be prevented by prompt testing for PVL-SA in individuals with a history of abscesses or furunculosis, followed by decolonization measures.


Assuntos
Toxinas Bacterianas/metabolismo , Exotoxinas/metabolismo , Leucocidinas/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/metabolismo , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Pneumonia Necrosante/microbiologia , Estudos Retrospectivos , Infecções dos Tecidos Moles/microbiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/patologia , Infecções Estafilocócicas/terapia
2.
J Agric Food Chem ; 67(39): 10863-10870, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31507180

RESUMO

Mastitis, inflammation of the mammary gland, occurs in both humans and animals. Staphylococcus aureus is the most common infectious bacterial pathogen associated with mastitis. We investigated the effects of allicin on S. aureus-induced mastitis in mice. Pathological histology revealed that allicin inhibited S. aureus-induced pathological damage and myeloperoxidase activity in mammary tissues. Enzyme-linked immunosorbent assays demonstrated that allicin reduced the production of IL-1ß and TNF-α as well as inhibited the NF-κB and mitogen-activated protein kinase pathway by reducing phosphorylation of p65, IκBα, p38, JNK, and ERK. Western blotting revealed that allicin reduced TLR2 and TLR6 expression in mammary tissues and cells but not in HEK293 cells. The lipid raft content was reduced by allicin, which inhibited signaling downstream of TLR2 and TLR6. Liver X receptor α (LXRα) luciferase reporter assays and LXRα interference experiments showed that allicin improved the LXRα activity and adenosine 5'-triphosphate-binding cassette G and A1 (ABCG and ABCA1) expression, thereby reducing the cholesterol level, lipid raft formation, and downstream TLR2 and TLR6 pathway activity. These results demonstrated that allicin exerted anti-inflammatory effects against S. aureus mastitis by improving the LXRα activity and reducing lipid raft formation.


Assuntos
Mastite/tratamento farmacológico , Microdomínios da Membrana/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Ácidos Sulfínicos/administração & dosagem , Animais , Feminino , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , Mastite/genética , Mastite/metabolismo , Mastite/microbiologia , Microdomínios da Membrana/química , Microdomínios da Membrana/genética , Microdomínios da Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/genética , NF-kappa B/metabolismo , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo
3.
Artigo em Inglês | MEDLINE | ID: mdl-31522665

RESUMO

From 1 January to 31 December 2017, 36 institutions around Australia participated in the Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP). The aim of ASSOP 2017 was to determine the proportion of Staphylococcus aureus bacteraemia (SAB) isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to methicillin and to characterise the molecular epidemiology of the methicillin-resistant isolates. A total of 2,515 S. aureus bacteraemia episodes were reported, of which 77% were community-onset. Approximately one in five S. aureus (19.0%) were methicillin resistant. The 30-day all-cause mortality associated with methicillin-resistant SAB was 18.7% which was significantly higher than the 14.0% mortality associated with methicillin-susceptible SAB. With the exception of the ß-lactams and erythromycin, antimicrobial resistance in methicillin-susceptible S. aureus was rare. However in addition to the ß-lactams approximately 42% of methicillin-resistant S. aureus (MRSA) were resistant to erythromycin and ciprofloxacin and approximately 14% resistant to co-trimoxazole, tetracycline and gentamicin. When applying the EUCAST breakpoints teicoplanin resistance was detected in five S. aureus isolates. Resistance was not detected for vancomycin and linezolid. Resistance to non-beta-lactam antimicrobials was largely attributable to two healthcare-associated MRSA clones: ST22-IV [2B] (EMRSA-15) and ST239-III [3A] (Aus-2/3 EMRSA). ST22-IV [2B] (EMRSA-15) is the predominant healthcare-associated clone in Australia. Seventy-five percent of methicillin-resistant SAB were due to community-associated clones. Although polyclonal approximately 74% of community-associated clones were characterised as ST93-IV [2B] (Queensland CA-MRSA), ST5-IV [2B], ST45-VT [5C2&5] and ST1-IV [2B]. CA-MRSA, in particular the ST45-VT [5C2&5] clone has acquired multiple antimicrobial resistance determinants including ciprofloxacin, erythromycin, clindamycin, gentamicin and tetracycline. ST45-VT [5C2&5] accounted for 12.8% of CA-MRSA. As CA-MRSA is well established in the Australian community it is important antimicrobial resistance patterns in community- and healthcare-associated SAB is monitored as this information will guide therapeutic practices in treating S. aureus sepsis.


Assuntos
Anti-Infecciosos/farmacologia , Bacteriemia/epidemiologia , Farmacorresistência Bacteriana Múltipla , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Bacteriemia/microbiologia , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pessoa de Meia-Idade , Epidemiologia Molecular , Infecções Estafilocócicas/microbiologia , Adulto Jovem
4.
Fortschr Neurol Psychiatr ; 87(9): 499-502, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31519025

RESUMO

Strains of methicillin-resistant Staphylococcus aureus (MRSA) are of major economic and health-related importance to early neurological and neurosurgical rehabilitation. It is crucial to identify MRSA-carriers as soon as possible upon admission in order to prevent transmissions and to initiate contact precautions and decolonization. The present study focuses on validity of a polymerase chain reaction (PCR) test to identify MRSA genetic material from nasopharyngeal samples (BD MAX MRSA XT, BD Diagnostics, Heidelberg, Germany) of early neurological and neurosurgical rehabilitation patients. PCR-results were compared to gold standard (culture). In 2013, 66 patients were tested using PCR and incubation within one week after admission. Sensitivity of PCR was 84.6 %, specificity 86.6 %. Positive predictive value (PPV) was only 61.1 %, while negative predictive value was as high as 95.8 %. In 39 cases, PCR and subsequent culture were done within one day, leading to a sensitivity of 100 % and a specificity of 90.3 %. In this subgroup, PPV was 72.7 %, NPV 100 %. The results from the study suggest that incubation should quickly follow a positive PCR finding (within 24 hours) in order to verify MRSA colonization. High NPV (95.8 resp. 100 %) indicate that PCR negative patients very likely are not colonized with MRSA. A positive PCR test is less reliable (due to false positive results) and should be followed by incubation in due course in order to avoid unnecessary contact precautions.


Assuntos
Programas de Rastreamento/normas , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Reabilitação Neurológica , Reação em Cadeia da Polimerase/normas , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Alemanha , Humanos , Sensibilidade e Especificidade
5.
J Agric Food Chem ; 67(36): 10222-10234, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31385700

RESUMO

The emergence and rapid spread of methicillin-resistant Staphylococcus aureus (MRSA) critically requires alternative therapeutic options. New antibacterial drugs and strategies are urgently needed to combat MRSA-associated infections. Here, we investigated the antibacterial activity of flavones from Morus alba and the potential mode of action against MRSA. Kuwanon G, kuwanon H, mulberrin, and morusin displayed high efficiency in killing diverse MRSA isolates. On the basis of structure-activity analysis, the cyclohexene-phenyl ketones and isopentenyl groups were critical to increase the membrane permeability and to dissipate the proton motive force. Meanwhile, mechanistic studies further showed that kuwanon G displayed rapid bactericidal activity in vitrowith difficulty in developing drug resistance. Kuwanon G targeted phosphatidylglycerol and cardiolipin in the cytoplasmic membrane through the formation of hydrogen bonds and electrostatic interactions. Additionally, kuwanon G promoted wound healing in a mouse model of MRSA skin infection. In summary, these results indicate that flavones are promising lead compounds to treat MRSA-associated infections through disrupting the proton motive force and membrane permeability.


Assuntos
Antibacterianos/farmacologia , Flavonas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/metabolismo , Morus/química , Extratos Vegetais/farmacologia , Infecções Estafilocócicas/microbiologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Permeabilidade da Membrana Celular/efeitos dos fármacos , Feminino , Flavonas/química , Flavonas/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Humanos , Masculino , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Raízes de Plantas/química , Força Próton-Motriz/efeitos dos fármacos
6.
APMIS ; 127(11): 717-726, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31407405

RESUMO

This study aims to determine the prevalence of Staphylococcus aureus colonizing patients and ICU environment of a teaching hospital, the virulence and antimicrobial susceptibility profile of the isolates, and to evaluate the genetic relationship among them. A total of 536 swabs (134 of patients and 402 of ICU environment) were collected and analyzed to detect S. aureus. The antimicrobial susceptibility of the isolates was determined by disk diffusion test, and the detection of the mecA and virulence factors genes was performed by PCR, in addition to SCCmec typing. The genetic similarity of the isolates was determined by PFGE. Staphylococcus aureus was isolated in 12.7% of the swabs. The prevalence of colonization was 13.4% in patients and 12.4% in the environmental samples. The multidrug resistance was determined in 82.4% of the isolates. The prevalence of methicillin-resistant S. aureus was 20.6%, with 50.0% classified as SCCmec IV. The intermediate resistance to vancomycin was detected in 5.9% and 4.4% of the isolates obtained from patients and environment, respectively. Identical isolates obtained from different patients and sources were grouped into several clusters. The results showed dissemination of multidrug-resistant strains between patients and fomites and the persistence of MRSA and VISA isolates in the ICU environment.


Assuntos
Antibacterianos/farmacologia , Resistência a Meticilina , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana , Feminino , Variação Genética , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Filogenia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Vancomicina/farmacologia , Virulência , Fatores de Virulência/genética
7.
Microb Pathog ; 135: 103616, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31283961

RESUMO

The antibiotic resistance among coagulase - negative Staphylococcus (CoNS) species towards methicillin is rarely reported in veterinary medicine. Under the aspect/concept of One Health, those strains pose a risk to human health due to the presence in canine pets where the transfer of resistant genetic markers might occur to other staphylococci species. The aim of this study was to investigate the antimicrobial resistance pattern among Coagulase Negative Staphylococci (CoNS) isolated from asymptomatic dogs and those affected by topic infections. Swabs from 254 dogs were first seeded in Mannitol Salt Agar. Species identification was conducted by Matrix Assisted Laser Desorption ionization - time of flight (MALDI-TOF ms) as previously described. The susceptibility test was performed by disk diffusion according to CLSI standards. Detection of mecA gene was performed. CoNS could be recovered from both groups of dogs and an alarming presence of methicillin-resistant coagulase negative staphylococci (MRCoNS) was confirmed, in 10.2% (17/166) of the samples. Eight of those methicillin resistant strains were isolated from asymptomatic dogs whereas nine were present in dogs affected by pyoderma and otitis externa.


Assuntos
Coagulase/deficiência , Reservatórios de Doenças/microbiologia , Doenças do Cão/microbiologia , Resistência a Meticilina , Infecções Estafilocócicas/veterinária , Staphylococcus/isolamento & purificação , Animais , Antibacterianos/farmacologia , Doenças do Cão/transmissão , Cães , Farmacorresistência Bacteriana , Genes Bacterianos , Humanos , Resistência a Meticilina/genética , Testes de Sensibilidade Microbiana , Proteínas de Ligação às Penicilinas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/transmissão , Staphylococcus/classificação , Staphylococcus/enzimologia , Staphylococcus/genética
8.
J Med Microbiol ; 68(9): 1367-1372, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31329093

RESUMO

Methicillin-resistant Staphylococcus lugdunensis (MRSL) is increasingly recognized in healthcare and community settings. To obtain a better understanding of the emergence of MRSL, this study characterized the structure and content of the SCCmec elements harboured by 36 MRSL isolates obtained from diverse sources in Hong Kong from 2008 to 2017. The isolates were investigated by whole-genome sequencing. SCCmec types and subtypes were assigned according to the guidelines from the International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements. The sequence type (ST)-SCCmec combinations in the 36 MRSL isolates were as follows: ST3-SCCmec IV (n=2), ST3-SCCmec V (n=28), ST27-SCCmec V (n=5) and ST42-SCCmec V (n=1). The two SCCmec IV elements were highly similar to the SCCmec IV element harboured by the community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain, JCSC6668. The J3-mec complex-J2 regions in the SCCmec V elements were highly similar to the corresponding regions in the CA-MRSA strains PM1 (n=13) or WIS (n=21). Based on the J1 to J3 sequences, the SCCmec V elements can be categorized into nine different subtypes. Our findings highlight the diversified structures of SCCmec elements among MRSL strains and their close relationship with SCCmec elements harboured by CA-MRSA.


Assuntos
Cromossomos Bacterianos/genética , Infecções Comunitárias Adquiridas/microbiologia , Genes Bacterianos/genética , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/microbiologia , Staphylococcus lugdunensis/genética , Antibacterianos/farmacologia , Infecções Comunitárias Adquiridas/epidemiologia , DNA Bacteriano/genética , Genoma Bacteriano/genética , Hong Kong/epidemiologia , Humanos , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Análise de Sequência de DNA , Infecções Estafilocócicas/epidemiologia , Estudantes de Medicina
9.
BMC Public Health ; 19(1): 914, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288765

RESUMO

BACKGROUND: The first Canadian outbreak of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was identified in 2004 in Calgary, Alberta. Using a novel model of MRSA population-based surveillance, sociodemographic risk associations, yearly geospatial dissemination and prevalence of CA-MRSA infections over an 11 year period was identified in an urban healthcare jurisdiction of Calgary. METHODS: Positive MRSA case records, patient demographics and laboratory data were obtained from a centralized Laboratory Information System of Calgary Laboratory Services in Calgary, Alberta, Canada between 2004 and 2014. Public census data was obtained from Statistics Canada, which was used to match with laboratory data and mapped using Geographic Information Systems. RESULTS: During the study period, 52.5% of positive MRSA infections in Calgary were CA-MRSA cases. The majority were CMRSA10 (USA300) clones (94.1%; n = 4255), while the remaining case (n = 266) were CMRSA7 (USA400) clones. Period prevalence of CMRSA10 increased from 3.6 cases/100000 population in 2004, to 41.3 cases/100000 population in 2014. Geospatial analysis demonstrated wide dissemination of CMRSA10 annually in the city. Those who are English speaking (RR = 0.05, p <  0.0001), identify as visible minority Chinese (RR = 0.09, p = 0.0023) or visible minority South Asian (RR = 0.25, p = 0.015), and have a high median household income (RR = 0.27, p <  0.0001) have a significantly decreased relative risk of CMRSA10 infections. CONCLUSIONS: CMRSA10 prevalence increased between 2004 and 2007, followed by a stabilization of cases by 2014. Certain sociodemographic factors were protective from CMRSA10 infections. The model of MRSA population-surveillance and geomap outbreak events can be used to track the epidemiology of MRSA in any jurisdiction.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Vigilância da População , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Adulto , Alberta/epidemiologia , Feminino , Sistemas de Informação Geográfica , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Análise Espacial
10.
Nat Commun ; 10(1): 2992, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278250

RESUMO

Lysocin E, a 37-membered natural depsipeptide, induces rapid bacteriolysis in methicillin-resistant Staphylococcus aureus via a unique menaquinone-dependent mechanism, presenting a promising therapeutic lead. Despite the great medical importance, exploring the potential utility of its derivatives as new platform structures for antibiotic development has remained a significant challenge. Here, we report a high-throughput strategy that enabled the preparation of thousands of analogues of lysocin E and large-scale structure-activity relationship analyses. We integrate 26-step total synthesis of 2401 cyclic peptides, tandem mass spectrometry-sequencing, and two microscale activity assays to identify 23 candidate compounds. Re-synthesis of these candidates shows that 11 of them (A1-A11) exhibit antimicrobial activity superior or comparable to that of lysocin E, and that lysocin E and A1-A11 share L-Leu-6 and L-Ile-11. Therefore, the present strategy allows us to efficiently decipher biologically crucial residues and identify potentially useful agents for the treatment of infectious diseases.


Assuntos
Antibacterianos/farmacologia , Descoberta de Drogas/métodos , Ensaios de Triagem em Larga Escala/métodos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Química Farmacêutica/métodos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Peptídeos Cíclicos/química , Peptídeos Cíclicos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem/métodos
12.
Medicine (Baltimore) ; 98(27): e16015, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277095

RESUMO

The aim of this study was to describe the clinical features of bone and joint infections (BJI) due to Panton-Valentine Leukocidin producing (PVL+) Staphylococcus aureus (SA) in French Guiana.A multicenter study that consists of a retrospective charts review of children admitted for PVL+ S. aureus BJI between January 2010 and December 2015.Six patients with SA-PVL BJI were identified during the study period: 2 osteomyelitis, 1 septic arthritis, and 3 disseminated BJI. The median age was 11 years old (4-14 years), and fever lasted for 3.2 days (2-5 days) before diagnosis. An open skin wound preceded the BJI in 5/6 patients. One patient presented with a septic thrombophlebitis of the femoral-popliteal vein on admission. Methicillin-susceptible Staphylococcus aureus (MSSA) were identified for all patients. Three patients had complications: 2 cases of necrotizing pneumonia and 2 pericarditis, with 1 death caused by cardiac tamponade.SA-PVL BJI was not frequent. Strains were susceptible to methicillin, but responsible of severe BJI. Early diagnosis and a multidisciplinary management of these infections are essential to prevent further complications.


Assuntos
Artrite Infecciosa/microbiologia , Toxinas Bacterianas/análise , Exotoxinas/análise , Leucocidinas/análise , Osteomielite/microbiologia , Infecções Estafilocócicas/microbiologia , Adolescente , Antibacterianos/uso terapêutico , Artrite Infecciosa/terapia , Proteína C-Reativa/análise , Criança , Pré-Escolar , Guiana Francesa , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Osteomielite/terapia , Estudos Retrospectivos , Infecções Estafilocócicas/terapia
13.
J Agric Food Chem ; 67(30): 8382-8392, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31271032

RESUMO

Staphylococcus aureus is a common pathogen that can cause life-threatening infections. Treatment of antibiotic-resistant S. aureus infection needs effective antibacterial agents. Thymol, a generally recognized safe natural compound, has potential as an alternative to treat S. aureus infections. However, the targets and mechanisms of action of thymol were not fully understood. Bioinformatics analysis showed that IolS, a predicted aldo-keto reductase (AKR) in S. aureus, could be a potential target of thymol. Isothermal titration calorimetry (ITC) analysis demonstrated that thymol directly binds IolS and amino acid residues (Y30 and L33) are essential for such binding. Deletion of IolS or mutation of Y30A and L33A reduced the bactericidal activity of thymol at the concentration of 200 µg/mL, suggesting that thymol mediates bactericidal activity via binding with IolS. Biochemical analysis showed that addition of thymol significantly increased AKR activity of IolS from 1.6 ± 0.1 to 2.4 ± 0.2 U (p < 0.05). The content of NADPH within S. aureus cells decreased significantly from 105 ± 5 to 72 ± 3 pmol/108 cells (p < 0.05) following thymol treatment at the concentration of 200 µg/mL. Importantly, addition of NADPH could alleviate the bactericidal effect of thymol on S. aureus, indicating that the depletion of NADPH is responsible for thymol-mediated bactericidal activity. Overall, these results demonstrated that thymol could directly bind IolS and increase its AKR activity, leading to the depletion of NADPH and bactericidal effect. AKR activity of IolS could be a promising target for the development of new antimicrobials.


Assuntos
Aldo-Ceto Redutases/antagonistas & inibidores , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , NADP/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/enzimologia , Timol/farmacologia , Aldo-Ceto Redutases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética
14.
BMC Vet Res ; 15(1): 238, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291949

RESUMO

BACKGROUND: Mupirocin is one of the few antimicrobials active against methicillin-resistant Staphylococcus aureus (MRSA), and is frequently used for the eradication of MRSA nasal colonisation in humans. Initially, mupirocin resistance was recognised in human S. aureus, including MRSA isolates, then also among coagulase-negative staphylococci (CoNS). Nowadays, mupirocin resistance is occasionally observed in canine staphylococci, along with Staphylococcus pseudintermedius (MRSP) strains, as well as CoNS, which usually show methicillin resistance. In the current study, high-level mupirocin resistance in methicillin-resistant staphylococci isolated from diseased dogs and cats was investigated. RESULTS: Among 140 methicillin-resistant staphylococci isolates from dogs and cats, three showed high-level mupirocin resistance in a screening test using the agar disk diffusion method. One was recognised as methicillin-resistant S. aureus, one as methicillin-resistant S. pseudintermedius, and one as methicillin-resistant Staphylococcus haemolyticus. S. pseudintermedius and S. aureus were isolated from dogs, S. haemolyticus was obtained from a cat. All isolates showed high-level mupirocin resistance, confirmed by minimum inhibitory concentration (MIC) values of above 1024 µg/ml and the presence of the plasmid-located gene ileS2. This is the first report on the detection of high-level mupirocin resistance (HLMR) in S. haemolyticus of feline origin. CONCLUSIONS: This study revealed the occurrence of HLMR in three Staphylococcus isolates obtained from companion animals in Poland. The results of this study indicate that the monitoring of mupirocin resistance in staphylococci of animal origin, especially in methicillin-resistant isolates, is strongly recommended.


Assuntos
Doenças do Gato/microbiologia , Doenças do Cão/microbiologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Mupirocina/farmacologia , Infecções Estafilocócicas/veterinária , Animais , Antibacterianos/farmacologia , Gatos , Cães , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologia
16.
Vet Res ; 50(1): 49, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221210

RESUMO

An ethanolic extract from Rhodomyrtus tomentosa leaves (RTL) was studied as a natural alternative to control Staphylococcus aureus, which is an important pathogen responsible for bovine mastitis. The minimal inhibitory concentrations (MICs) of the RTL extract and of rhodomyrtone, a pure compound isolated from the plant, were determined by a microdilution method. Rhodomyrtone and the RTL extract exhibited antibacterial activity against S. aureus, including its persistent phenotype (SCV: small-colony variant) and a biofilm hyperproducer strain, with MICs of 0.25-0.5 and 8-16 µg/mL, respectively. Time-kill kinetics showed a strong bactericidal activity for both the RTL extract- and rhodomyrtone-treated bacteria at 2 × MIC as early as 4 h post-exposure. An additive effect of the extract at 0.5 × MIC was observed in a combination with oxytetracycline or pirlimycin against S. aureus by showing a 64- to 128-fold reduction in antibiotic MICs. Moreover, the RTL extract significantly decreased the number of intracellular SCVs inside bovine mammary epithelial cells. However, the extract or its combination with pirlimycin only slightly improved the activity of pirlimycin against the bacterial colonization of mouse mammary glands. In vitro MICs determined in the presence of casein indicated that the limited activity of the RTL extract in the murine model of mastitis could be linked to neutralization of active components by milk proteins. While the RTL extract showed interesting antibacterial properties in vitro, to be considered as an alternative to antibiotics in dairy farms, formulation studies are needed to cope with the observed reduction of activity in vivo.


Assuntos
Antibacterianos/farmacologia , Mastite Bovina/tratamento farmacológico , Myrtaceae/química , Extratos Vegetais/farmacologia , Infecções Estafilocócicas/veterinária , Staphylococcus aureus/efeitos dos fármacos , Animais , Bovinos , Modelos Animais de Doenças , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Feminino , Mastite Bovina/microbiologia , Camundongos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Xantonas/farmacologia
17.
Int J Food Microbiol ; 305: 108244, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31202150

RESUMO

This study examined the prevalence and phenotypic and genotypic antibiotic resistance patterns of Staphylococcus aureus in sushi from 20 Danish outlets. Microbial quality of sushi products and food inspector ranking of outlets were assessed and results for thirteen of the outlets were compared with findings from a previous study in 2012. Inspector rankings were similar in the two studies. The mesophilic aerobic counts were slightly lower (p = 0.0296) in 2017 than in 2012 with average values of the 13 shops of 5.2 log CFU/g and 5.7 log CFU/g, respectively. In both studies E. coli was only found in the products from outlets that did not have consistently superior rankings. On the other hand prevalence and average counts of Staphylococcus spp. were slightly higher in 2017 (p = 0.0286) but no methicillin-resistant S. aureus (MRSA) were observed in the present study. Methicillin-sensitive S. aureus (MSSA) were, however, isolated from 18.7% of sushi products with an average count below 2 log CFU/g. Based on spa and multilocus sequence typing (MLST), isolates belonged to clonal complex CC7 (t2016), CC20 (t7836), CC45 (t065, t127, t362), CC88 (t1998) and CC398 (t164, t331, t1451). The Panton-Valentine leukocidin (PVL)-encoding gene lukF was detected only in isolates of the t065 spa-type whereas the scn gene from the ΦSa3 prophage was detected in 76.5% of the isolates, supporting that the majority of isolates were of likely human origin. Thirty-six isolates (70.6%) were resistant to at least one of the antibiotic compounds tested. Antibiotic resistance genes that confer resistance to ß-lactams (blaZ) and macrolides (ermC) were detected in 33.3% and 9.8% of isolates, respectively. The tet(K) gene that encode tetracycline resistance was only found in a t7836 strain. Overall, this study indicates that S. aureus in sushi products in Denmark do not represent a major food safety hazard due to, firstly, the low temperature and limited time of storage of product may prevent significant growth and production of toxic levels of enterotoxin of this species. Secondly, the S. aureus isolates obtained did not include MRSA variants and none of them encoded PVL that constitute one of the virulence factors in pathogenesis. Several MSSA isolates contained however genes encoding antibiotic resistance, which emphasize the potential role of foods as vehicles for transmission of such variants.


Assuntos
Farmacorresistência Bacteriana , Produtos Pesqueiros/microbiologia , Inspeção de Alimentos/normas , Animais , Antibacterianos/farmacologia , Dinamarca , Escherichia coli/classificação , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Peixes , Humanos , Meticilina/farmacologia , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Fatores de Virulência/genética , beta-Lactamas/farmacologia
18.
Pan Afr Med J ; 32: 103, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223393

RESUMO

Introduction: Staphylococcus aureus is an important pathogen responsible for hospital and community acquired infection(s). Emerging resistance to methicillin in this organism has left physicians with few therapeutic alternatives to treat infections caused by it. This study was aimed at determining the antibiotic susceptibility patterns of Staphylococcus aureus strains isolated at the Yaounde Central Hospital, Cameroon. Methods: from January 2014 to November 2016, a total of 250 non repeated strains were isolated from various clinical specimens. Isolates and antibiotic susceptibility profiles were identified through standard microbiological techniques. Results: methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) accounted respectively for 80% (201/205) and 20% (49/205) of the total strains isolated. MRSA strains displayed high resistance to cefoxitin (100%), cotrimoxazole (89%), vancomycin (79.7%), lincomycin (70.3%), tobramycin (72.5%), doxycycline (68.0%), kanamycin (69.7%) and erythromycin (55.7%). In contrast, a high susceptibility was observed with rifampicin (82.6%). KTG (42.3%) and constitutive MLSB (17.4%) were the most frequent phenotypes recorded. Conclusion: our results show that the carriage of acquired MRSA infections predominates in this population. Despite the noticeable multiresistance of MRSA strains to antibiotics, rifampicin remains the drugs of choice for the therapy of acquired MRSA infections in this setting. In order to slow down antimicrobial resistance, surveillance studies for antimicrobial susceptibility remains essential to identify resistance and inform policy on resistance.


Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Camarões/epidemiologia , Estudos Transversais , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Estudos Prospectivos , Estudos Retrospectivos , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação
19.
Ann R Coll Surg Engl ; 101(7): e154-e156, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31155912

RESUMO

Infected pseudoaneurysms are a vascular emergency, necessitating urgent surgical management. Owing to the infected field, a synthetic graft may be inappropriate in patients for whom autografting is impossible. Ligation of the artery is the usual management, often leading to amputation. We report a case of cadaveric allografting of the common femoral artery in a patient with a traumatic, infected pseudoaneurysm, who was taking immunosuppressive therapy for a liver transplant. The patient was followed up with ultrasound at 12 months and was found to have a significant graft stenosis, which was treated successfully with angioplasty. At 18 months, the patient remained well. This case describes the successful implantation of a cadaveric allograft into a patient with an infected pseudoaneurysm, negating the for need primary ligation.


Assuntos
Falso Aneurisma/cirurgia , Veia Femoral/transplante , Flebotomia/efeitos adversos , Infecções Estafilocócicas/cirurgia , Enxerto Vascular/métodos , Adulto , Aloenxertos/transplante , Falso Aneurisma/diagnóstico , Falso Aneurisma/etiologia , Falso Aneurisma/microbiologia , Cadáver , Angiografia por Tomografia Computadorizada , Artéria Femoral/cirurgia , Veia Femoral/diagnóstico por imagem , Veia Femoral/lesões , Veia Femoral/microbiologia , Virilha , Humanos , Extremidade Inferior/irrigação sanguínea , Masculino , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento
20.
Nat Commun ; 10(1): 2730, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227691

RESUMO

Recently our groups discovered lugdunin, a new cyclic peptide antibiotic that inhibits Staphylococcus aureus epithelial colonization in humans and rodents. In this work, we analyzed its immuno-modulatory and antimicrobial potential as a single agent or in combination with other microbiota- or host-derived factors. We show that pretreatment of primary human keratinocytes or mouse skin with lugdunin in combination with microbiota-derived factors results in a significant reduction of S. aureus colonization. Moreover, lugdunin increases expression and release of LL-37 and CXCL8/MIP-2 in human keratinocytes and mouse skin, and results in the recruitment of monocytes and neutrophils in vivo, both by a TLR/MyD88-dependent mechanism. Interestingly, S. aureus elimination by lugdunin is additionally achieved by synergistic antimicrobial activity with LL-37 and dermcidin-derived peptides. In summary, our results indicate that lugdunin provides multi-level protection against S. aureus and may thus become a promising treatment option for S. aureus skin infections in the future.


Assuntos
Antibacterianos/farmacologia , Imunidade Inata/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Tiazolidinas/farmacologia , Animais , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/imunologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microbiota/efeitos dos fármacos , Microbiota/imunologia , Peptídeos/imunologia , Peptídeos Cíclicos/uso terapêutico , Cultura Primária de Células , Pele/efeitos dos fármacos , Pele/imunologia , Pele/microbiologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Tiazolidinas/uso terapêutico
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