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[PMID]:29295973
[Au] Autor:Blaskovich MAT; Hansford KA; Gong Y; Butler MS; Muldoon C; Huang JX; Ramu S; Silva AB; Cheng M; Kavanagh AM; Ziora Z; Premraj R; Lindahl F; Bradford TA; Lee JC; Karoli T; Pelingon R; Edwards DJ; Amado M; Elliott AG; Phetsang W; Daud NH; Deecke JE; Sidjabat HE; Ramaologa S; Zuegg J; Betley JR; Beevers APG; Smith RAG; Roberts JA; Paterson DL; Cooper MA
[Ad] Endereço:Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, 4072, Australia. m.blaskovich@uq.edu.au.
[Ti] Título:Protein-inspired antibiotics active against vancomycin- and daptomycin-resistant bacteria.
[So] Source:Nat Commun;9(1):22, 2018 01 02.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The public health threat posed by a looming 'post-antibiotic' era necessitates new approaches to antibiotic discovery. Drug development has typically avoided exploitation of membrane-binding properties, in contrast to nature's control of biological pathways via modulation of membrane-associated proteins and membrane lipid composition. Here, we describe the rejuvenation of the glycopeptide antibiotic vancomycin via selective targeting of bacterial membranes. Peptide libraries based on positively charged electrostatic effector sequences are ligated to N-terminal lipophilic membrane-insertive elements and then conjugated to vancomycin. These modified lipoglycopeptides, the 'vancapticins', possess enhanced membrane affinity and activity against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive bacteria, and retain activity against glycopeptide-resistant strains. Optimised antibiotics show in vivo efficacy in multiple models of bacterial infection. This membrane-targeting strategy has potential to 'revitalise' antibiotics that have lost effectiveness against recalcitrant bacteria, or enhance the activity of other intravenous-administered drugs that target membrane-associated receptors.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Bactérias/efeitos dos fármacos
Daptomicina/farmacologia
Farmacorresistência Bacteriana/efeitos dos fármacos
Proteínas de Membrana/metabolismo
Vancomicina/farmacologia
[Mh] Termos MeSH secundário: Animais
Antibacterianos/metabolismo
Antibacterianos/farmacocinética
Bactérias/classificação
Sobrevivência Celular/efeitos dos fármacos
Glicopeptídeos/metabolismo
Células HEK293
Células Hep G2
Seres Humanos
Masculino
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Camundongos
Testes de Sensibilidade Microbiana
Viabilidade Microbiana/efeitos dos fármacos
Staphylococcus aureus/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Glycopeptides); 0 (Membrane Proteins); 6Q205EH1VU (Vancomycin); NWQ5N31VKK (Daptomycin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02123-w


  2 / 1688 MEDLINE  
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[PMID]:29390580
[Au] Autor:Xu P; Zeng H; Zhou M; Ouyang J; Chen B; Zhang Q
[Ti] Título:Successful management of a complicated clinical crisis: A patient with left-sided endocarditis and secondary hemophagocytic lymphohistiocytosis: a rare case report and literature review.
[So] Source:Medicine (Baltimore);96(51):e9451, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Hemophagocytic lymphohistiocytosis (HLH) secondary to methicillin-resistant Staphylococcus epidermidis (MRSE)-related left-sided infectious endocarditis had never been reported before. In the last decade, daptomycin, a novel lipopeptide antibiotic, showed its excellent role in anti-Gram-positive bacteria, including soft tissue infection, bloodstream and deep tissueinfection. PATIENT CONCERNS: An Asian women under sever condition due to the cooccurrence of HLH and MRSE-related endocarditis while also be allergic to vancomycin. The patient was cured by high-dose daptomycin monotheraphy, HLH-2004 protocol and cardiothoracic surgery to remove the valve at last, and was obviously benefit from the endeavor of a multidisciplinary team (MDT) strategy. DIAGNOSES: IE was made on March 27according to the modified Duke criteria. HLH was diagnosed too. INTERVENTIONS: The patient was cured by high-dose daptomycin monotheraphy, HLH-2004 protocol and cardiothoracic surgery to remove the valve at last, and was obviously benefit from the endeavor of a multidisciplinary team (MDT) strategy. OUTCOMES: The patient was healthy andstable when we published this case. LESSONS: This case proves high-dose daptomycin monotheraphy could be used as an effective alternative regimen for vancomycin in treating MRSE-related left-sided endocarditis and highlight the importance of early diagnosis and appropriate management for HLH. Furthermore, our work suggests an MDT model as a practical strategy in managing similar clinical situation.
[Mh] Termos MeSH primário: Endocardite Bacteriana/complicações
Linfo-Histiocitose Hemofagocítica/complicações
Staphylococcus aureus Resistente à Meticilina
Infecções Estafilocócicas/complicações
[Mh] Termos MeSH secundário: Adulto
Antibacterianos/uso terapêutico
Terapia Combinada
Daptomicina/uso terapêutico
Endocardite Bacteriana/microbiologia
Endocardite Bacteriana/cirurgia
Endocardite Bacteriana/terapia
Feminino
Seres Humanos
Linfo-Histiocitose Hemofagocítica/etiologia
Linfo-Histiocitose Hemofagocítica/microbiologia
Infecções Estafilocócicas/microbiologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); NWQ5N31VKK (Daptomycin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009451


  3 / 1688 MEDLINE  
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[PMID]:29195768
[Au] Autor:Menon V; Davis R; Shackel N; Espedido BA; Beukers AG; Jensen SO; van Hal SJ
[Ad] Endereço:Department of Microbiology and Infectious Diseases, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
[Ti] Título:Failure of daptomycin ß-Lactam combination therapy to prevent resistance emergence in Enterococcus faecium.
[So] Source:Diagn Microbiol Infect Dis;90(2):120-122, 2018 Feb.
[Is] ISSN:1879-0070
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Daptomycin ß-Lactam combination therapy offers "protection" against daptomycin non-susceptibility (DNS) development in Enterococcus faecium. We report failure of this strategy and the importance of source control. Mutations were detected in the LiaF and cls genes in DNS isolates. A single DNS isolate contained an unrecognized mutation, which requires confirmation.
[Mh] Termos MeSH primário: Antibacterianos/uso terapêutico
Daptomicina/uso terapêutico
Enterococcus faecium/efeitos dos fármacos
Infecções por Bactérias Gram-Positivas/tratamento farmacológico
beta-Lactamas/uso terapêutico
[Mh] Termos MeSH secundário: Idoso
Antibacterianos/farmacologia
Daptomicina/farmacologia
Farmacorresistência Bacteriana/genética
Quimioterapia Combinada
Enterococcus faecium/genética
Infecções por Bactérias Gram-Positivas/microbiologia
Seres Humanos
Masculino
Testes de Sensibilidade Microbiana
Mutação/genética
beta-Lactamas/farmacologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (beta-Lactams); NWQ5N31VKK (Daptomycin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180209
[Lr] Data última revisão:
180209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171203
[St] Status:MEDLINE


  4 / 1688 MEDLINE  
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[PMID]:29369189
[Au] Autor:Bartal C; Sagy I; Barski L
[Ti] Título:Drug-induced eosinophilic pneumonia: A review of 196 case reports.
[So] Source:Medicine (Baltimore);97(4):e9688, 2018 Jan.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND OBJECTIVE: Eosinophilic pneumonia (EP) is an important subset of patients who present with pulmonary infiltrates and eosinophilia (PIE). EP is classified by chronicity and etiology and drug-induced EP is the main cause of secondary EP. The primary goal of this review was to examine all the case reports published since the syndrome was defined in 1990. It remains unclear whether acute or chronic EP (AEP or CEP) represent different diseases, and the secondary goal of this review is to determine if there are factors that may help distinguish these 2 entities. METHODS: PubMed (MEDLINE and Medical Subject Headings) was searched for case reports of drug-induced EP or PIE syndrome published between 1990 and 2017. Case reports were only included if the diagnostic criteria for AEP or CEP were fulfilled. For each case, data were extracted pertaining to age, sex, type of medication associated with the disease, time from the onset of symptoms to diagnosis, eosinophil counts in the blood, eosinophil fractions in bronchoalveolar lavage (BAL) fluid, initial chest radiograph and computed tomography results, use of mechanical ventilation, and use of steroid treatment and recurrence. RESULTS: We found 196 case reports describing drug-induced EP. The leading cause was daptomycin. From our review, we found that AEP is more common in younger patients with no gender preference. Eosinophilia in the blood at the time of diagnosis characterized only the CEP patients (80% in CEP vs. 20% in AEP). Abnormal findings on radiographic imagine was similar in both syndromes. A significant portion of AEP patients (20%) presented with acute respiratory failure requiring mechanical ventilation. Most patients with EP were treated with steroids with a higher rate of relapse observed in patients with CEP. CONCLUSION: AEP is a much more fulminant and severe disease than the gradual onset and slowly progressive nature of CEP. The pathogenesis of AEP and CEP remains unclear. However, there is significant clinical overlap among AEP and CEP that are associated with drug toxicity, suggesting the possibility that AEP and CEP are distinct clinical presentations that share a common pathogenic pathway.
[Mh] Termos MeSH primário: Antibacterianos/efeitos adversos
Anti-Inflamatórios não Esteroides/efeitos adversos
Eosinofilia Pulmonar/induzido quimicamente
[Mh] Termos MeSH secundário: Doença Aguda
Adulto
Doença Crônica
Daptomicina/efeitos adversos
Eosinófilos
Feminino
Seres Humanos
Masculino
Mesalamina/efeitos adversos
Meia-Idade
Minociclina/efeitos adversos
Eosinofilia Pulmonar/sangue
Sulfassalazina/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Anti-Inflammatory Agents, Non-Steroidal); 3XC8GUZ6CB (Sulfasalazine); 4Q81I59GXC (Mesalamine); FYY3R43WGO (Minocycline); NWQ5N31VKK (Daptomycin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009688


  5 / 1688 MEDLINE  
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[PMID]:27775684
[Au] Autor:Pader V; Hakim S; Painter KL; Wigneshweraraj S; Clarke TB; Edwards AM
[Ad] Endereço:MRC Centre for Molecular Bacteriology and Infection, Imperial College London, Armstrong Road, London SW7 2AZ, UK.
[Ti] Título:Staphylococcus aureus inactivates daptomycin by releasing membrane phospholipids.
[So] Source:Nat Microbiol;2:16194, 2016 Oct 24.
[Is] ISSN:2058-5276
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Daptomycin is a bactericidal antibiotic of last resort for serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA) . Although resistance is rare, treatment failure can occur in more than 20% of cases and so there is a pressing need to identify and mitigate factors that contribute to poor therapeutic outcomes. Here, we show that loss of the Agr quorum-sensing system, which frequently occurs in clinical isolates, enhances S. aureus survival during daptomycin treatment. Wild-type S. aureus was killed rapidly by daptomycin, but Agr-defective mutants survived antibiotic exposure by releasing membrane phospholipids, which bound and inactivated the antibiotic. Although wild-type bacteria also released phospholipid in response to daptomycin, Agr-triggered secretion of small cytolytic toxins, known as phenol soluble modulins, prevented antibiotic inactivation. Phospholipid shedding by S. aureus occurred via an active process and was inhibited by the ß-lactam antibiotic oxacillin, which slowed inactivation of daptomycin and enhanced bacterial killing. In conclusion, S. aureus possesses a transient defence mechanism that protects against daptomycin, which can be compromised by Agr-triggered toxin production or an existing therapeutic antibiotic.
[Mh] Termos MeSH primário: Antibacterianos/metabolismo
Membrana Celular/efeitos dos fármacos
Daptomicina/metabolismo
Tolerância a Medicamentos
Fosfolipídeos/metabolismo
Staphylococcus aureus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Proteínas de Bactérias
Viabilidade Microbiana/efeitos dos fármacos
Staphylococcus aureus/genética
Transativadores/deficiência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Agr protein, Staphylococcus aureus); 0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Phospholipids); 0 (Trans-Activators); NWQ5N31VKK (Daptomycin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180126
[Lr] Data última revisão:
180126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1038/nmicrobiol.2016.194


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[PMID]:28700928
[Au] Autor:Lee MT; Hung WC; Hsieh MH; Chen H; Chang YY; Huang HW
[Ad] Endereço:National Synchrotron Radiation Research Center, Hsinchu, Taiwan; Department of Physics, National Central University, Jhongli, Taiwan.
[Ti] Título:Molecular State of the Membrane-Active Antibiotic Daptomycin.
[So] Source:Biophys J;113(1):82-90, 2017 Jul 11.
[Is] ISSN:1542-0086
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Membrane-active antibiotics are potential alternatives to the resistance-prone conventional antibiotics. Daptomycin, a cyclic lipopeptide, is the only membrane-active antibiotic approved by the U.S. Food and Drug Administration so far. The drug interacts with the cytoplasmic membranes of Gram-positive pathogens, causing membrane permeabilization to ions and cell death. The antibiotic activity is calcium-ion dependent and correlates with the target membrane's content of phosphatidylglycerol (PG). For such a complex reaction with membranes, it has been difficult to uncover the molecular process that underlies its antibacterial activity. The role of the cofactor, calcium ions, has been confusing. Many have proposed that calcium ions binding to daptomycin is a precondition for membrane interaction. Here, we report our findings on the molecular state of daptomycin before and after its membrane-binding reaction, particularly at therapeutic concentrations in the low micromolar range. We were able to perform small-angle x-ray scattering at sufficiently low daptomycin concentrations to determine that the molecules are monomeric before membrane binding. By careful circular dichroism (CD) analyses of daptomycin with Ca and PG-containing membranes, we found that there are only two states identifiable by CD, one before and another after membrane binding; all other CD spectra are linear combinations of the two. Before membrane binding, the molecular state of daptomycin as defined by CD is the same with or without calcium ions. We are able to determine the stoichiometric ratios of the membrane-binding reaction. The stoichiometric ratio of daptomycin to calcium is 2:3. The stoichiometric ratio of daptomycin to PG is ∼1:1 if only the PG lipids in the outer leaflets of membranes are accessible to daptomycin.
[Mh] Termos MeSH primário: Antibacterianos/química
Daptomicina/química
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Cálcio/química
Cátions Bivalentes/química
Dicroísmo Circular
Daptomicina/farmacologia
Modelos Moleculares
Fosfatidilcolinas/química
Fosfatidilgliceróis/química
Espalhamento a Baixo Ângulo
Lipossomas Unilamelares/química
Difração de Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Cations, Divalent); 0 (Phosphatidylcholines); 0 (Phosphatidylglycerols); 0 (Unilamellar Liposomes); 66322-31-4 (1,2-dioleoyl-sn-glycero-3-phosphoglycerol); EDS2L3ODLV (1,2-oleoylphosphatidylcholine); NWQ5N31VKK (Daptomycin); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170713
[St] Status:MEDLINE


  7 / 1688 MEDLINE  
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[PMID]:28542602
[Au] Autor:Barlow RS; McMillan KE; Duffy LL; Fegan N; Jordan D; Mellor GE
[Ad] Endereço:CSIRO Agriculture and Food, Coopers Plains, Queensland, Australia.
[Ti] Título:Antimicrobial resistance status of Enterococcus from Australian cattle populations at slaughter.
[So] Source:PLoS One;12(5):e0177728, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Antimicrobial agents are used in cattle production systems for the prevention and control of bacterial associated diseases. A consequence of their use is the potential development of antimicrobial resistance (AMR). Enterococcus faecium and Enterococcus faecalis that are resistant to antimicrobials are of increased concern to public health officials throughout the world as they may compromise the ability of various treatment regimens to control disease and infection in human medicine. Australia is a major exporter of beef; however it does not have an ongoing surveillance system for AMR in cattle or foods derived from these animals. This study examined 910 beef cattle, 290 dairy cattle and 300 veal calf faecal samples collected at slaughter for the presence of enterococci. Enterococcus were isolated from 805 (88.5%) beef cattle faeces, 244 (84.1%) dairy cattle faeces and 247 (82.3%) veal calf faeces with a total of 800 enterococci subsequently selected for AMR testing. The results of AMR testing identified high levels of resistance to antimicrobials that are not critically or highly important to human medicine with resistance to flavomycin (80.2%) and lincomycin (85.4-94.2%) routinely observed. Conversely, resistance to antibiotics considered critically or highly important to human medicine such as tigecycline, daptomycin, vancomycin and linezolid was not present in this study. There is minimal evidence that Australian cattle production practices are responsible for disproportionate contributions to AMR development and in general resistance to antimicrobials of critical and high importance in human medicine was low regardless of the isolate source. The low level of antimicrobial resistance in Enterococcus from Australian cattle is likely to result from comprehensive controls around the use of antimicrobials in food-production animals in Australia. Nevertheless, continued monitoring of the effects of all antimicrobial use is required to support Australia's reputation as a supplier of safe and healthy food.
[Mh] Termos MeSH primário: Matadouros
Antibacterianos/farmacologia
Bovinos/microbiologia
Farmacorresistência Bacteriana
Enterococcus faecalis/efeitos dos fármacos
Enterococcus faecium/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Austrália
Daptomicina/farmacologia
Enterococcus faecalis/genética
Enterococcus faecium/genética
Genótipo
Testes de Sensibilidade Microbiana
Minociclina/análogos & derivados
Minociclina/farmacologia
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 70JE2N95KR (tigecycline); FYY3R43WGO (Minocycline); NWQ5N31VKK (Daptomycin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177728


  8 / 1688 MEDLINE  
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[PMID]:28471867
[Au] Autor:Syrogiannopoulos GA; Michoula AN; Petinaki E; Grivea IN
[Ad] Endereço:From the *Department of Pediatrics, and †Department of Microbiology, University of Thessaly, School of Health Sciences, Faculty of Medicine, Larissa, Greece.
[Ti] Título:Daptomycin Use in Children: Experience With Various Types of Infection and Age Groups.
[So] Source:Pediatr Infect Dis J;36(10):962-966, 2017 Oct.
[Is] ISSN:1532-0987
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In Greece, there are high rates of methicillin (40%-60%) and clindamycin (15%-25%) resistance among community-acquired Staphylococcus aureus isolates. Therefore, we sought to identify other antimicrobial treatment options such as daptomycin. METHODS: We studied retrospectively all pediatric infections treated with daptomycin at the University General Hospital of Larissa, Greece, from January 1, 2007, to June 16, 2016. RESULTS: Of a total of 128 patients (median age: 2.8 years; range: 8 days to 14.5 years; 76.6% <7 years) treated with daptomycin, 45 (35.2%) had invasive infection, most frequently musculoskeletal, and 83 (64.8%) had noninvasive infection, that is, complicated skin and soft tissue infection. S. aureus was the most commonly recovered pathogen (n = 61) (63.9% methicillin-resistant isolates, 21.3% clindamycin-resistant). The average daily dose of daptomycin was 10 mg/kg qd, and the median duration of therapy was 10 days. Daptomycin was administered alone (n = 61) or in combination therapy (n = 67), most frequently with rifampin (n = 40) and/or a ß-lactam antibiotic (n = 33). Open or closed drainage was performed in 86 (67.2%) of the total number of patients. Of 128 treated patients, 123 (96.1%) achieved clinical success, 114 (89.1%) had complete remission, and 9 (7%) had improvement of their disease. There were no failures with daptomycin therapy. The adverse events were of no clinical significance. CONCLUSIONS: Daptomycin administered alone or in combination with other antimicrobial agents to children was efficacious and well tolerated in the treatment of complicated infections of suspected or proven staphylococcal etiology.
[Mh] Termos MeSH primário: Antibacterianos/uso terapêutico
Infecções Bacterianas/tratamento farmacológico
Daptomicina/uso terapêutico
Doenças Musculares/tratamento farmacológico
Infecções dos Tecidos Moles/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Antibacterianos/administração & dosagem
Infecções Bacterianas/epidemiologia
Infecções Bacterianas/microbiologia
Criança
Pré-Escolar
Daptomicina/administração & dosagem
Feminino
Grécia/epidemiologia
Seres Humanos
Lactente
Recém-Nascido
Masculino
Doenças Musculares/epidemiologia
Doenças Musculares/microbiologia
Estudos Retrospectivos
Infecções dos Tecidos Moles/epidemiologia
Infecções dos Tecidos Moles/microbiologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); NWQ5N31VKK (Daptomycin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1097/INF.0000000000001629


  9 / 1688 MEDLINE  
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[PMID]:28423018
[Au] Autor:Rashid R; Cazenave-Gassiot A; Gao IH; Nair ZJ; Kumar JK; Gao L; Kline KA; Wenk MR
[Ad] Endereço:Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore.
[Ti] Título:Comprehensive analysis of phospholipids and glycolipids in the opportunistic pathogen Enterococcus faecalis.
[So] Source:PLoS One;12(4):e0175886, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Enterococcus faecalis is a Gram-positive, opportunistic, pathogenic bacterium that causes a significant number of antibiotic-resistant infections in hospitalized patients. The development of antibiotic resistance in hospital-associated pathogens is a formidable public health threat. In E. faecalis and other Gram-positive pathogens, correlations exist between lipid composition and antibiotic resistance. Resistance to the last-resort antibiotic daptomycin is accompanied by a decrease in phosphatidylglycerol (PG) levels, whereas multiple peptide resistance factor (MprF) converts anionic PG into cationic lysyl-PG via a trans-esterification reaction, providing resistance to cationic antimicrobial peptides. Unlike previous studies that relied on thin layer chromatography and spectrophotometry, we have performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) directly on lipids extracted from E. faecalis, and quantified the phospholipids through multiple reaction monitoring (MRM). In the daptomycin-sensitive E. faecalis strain OG1RF, we have identified 17 PGs, 8 lysyl-PGs (LPGs), 23 cardiolipins (CL), 3 glycerophospho-diglucosyl-diacylglycerols (GPDGDAG), 5 diglucosyl-diacylglycerols (DGDAG), 3 diacylglycerols (DAGs), and 4 triacylglycerols (TAGs). We have quantified PG and shown that PG levels vary during growth of E. faecalis in vitro. We also show that two daptomycin-resistant (DapR) strains of E. faecalis have substantially lower levels of PG and LPG levels. Since LPG levels in these strains are lower, daptomycin resistance is likely due to the reduction in PG. This lipidome map is the first comprehensive analysis of membrane phospholipids and glycolipids in the important human pathogen E. faecalis, for which antimicrobial resistance and altered lipid homeostasis have been intimately linked.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Daptomicina/farmacologia
Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos
Enterococcus faecalis/efeitos dos fármacos
Lisina/metabolismo
Fosfatidilgliceróis/metabolismo
[Mh] Termos MeSH secundário: Biotransformação
Cardiolipinas/classificação
Cardiolipinas/isolamento & purificação
Cardiolipinas/metabolismo
Cromatografia Líquida
Diglicerídeos/classificação
Diglicerídeos/isolamento & purificação
Diglicerídeos/metabolismo
Farmacorresistência Bacteriana Múltipla/fisiologia
Enterococcus faecalis/crescimento & desenvolvimento
Enterococcus faecalis/metabolismo
Metabolismo dos Lipídeos
Lisina/classificação
Lisina/isolamento & purificação
Metabolômica
Fosfatidilgliceróis/classificação
Fosfatidilgliceróis/isolamento & purificação
Espectrometria de Massas em Tandem
Triglicerídeos/classificação
Triglicerídeos/isolamento & purificação
Triglicerídeos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Cardiolipins); 0 (Diglycerides); 0 (Phosphatidylglycerols); 0 (Triglycerides); 42241-11-2 (lysylphosphatidylglycerol); K3Z4F929H6 (Lysine); NWQ5N31VKK (Daptomycin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170505
[Lr] Data última revisão:
170505
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170420
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0175886


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[PMID]:28419033
[Au] Autor:Thompson JM; Saini V; Ashbaugh AG; Miller RJ; Ordonez AA; Ortines RV; Wang Y; Sterling RS; Jain SK; Miller LS
[Ad] Endereço:1Department of Orthopaedic Surgery (J.M.T., R.S.S., and L.S.M.), Department of Pediatrics (V.S., A.A.O., and S.K.J.), Center for Infection and Inflammation Imaging Research (V.S., A.A.O., and S.K.J.), Department of Dermatology (A.G.A., R.J.M., R.V.O., Y.W., and L.S.M.), and Division of Infectious Diseases, Department of Medicine (L.S.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland.
[Ti] Título:Oral-Only Linezolid-Rifampin Is Highly Effective Compared with Other Antibiotics for Periprosthetic Joint Infection: Study of a Mouse Model.
[So] Source:J Bone Joint Surg Am;99(8):656-665, 2017 Apr 19.
[Is] ISSN:1535-1386
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The medical treatment of periprosthetic joint infection (PJI) involves prolonged systemic antibiotic courses, often with suboptimal clinical outcomes including increased morbidity and health-care costs. Oral and intravenous monotherapies and combination antibiotic regimens were evaluated in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) PJI. METHODS: Oral linezolid with or without oral rifampin, intravenous vancomycin with oral rifampin, intravenous daptomycin or ceftaroline with or without oral rifampin, oral doxycycline, or sham treatment were administered at human-exposure doses for 6 weeks in a mouse model of PJI. Bacterial burden was assessed by in vivo bioluminescent imaging and ex vivo counting of colony-forming units (CFUs), and reactive bone changes were evaluated with radiographs and micro-computed tomography (µCT) imaging. RESULTS: Oral-only linezolid-rifampin and all intravenous antibiotic-rifampin combinations resulted in no recoverable bacteria and minimized reactive bone changes. Although oral linezolid was the most effective monotherapy, all oral and intravenous antibiotic monotherapies failed to clear infection or prevent reactive bone changes. CONCLUSIONS: Combination antibiotic-rifampin regimens, including oral-only linezolid-rifampin and the newer ceftaroline-rifampin combinations, were highly effective and more efficacious than monotherapies when used against a preclinical MRSA PJI. CLINICAL RELEVANCE: This study provides important preclinical evidence to better optimize future antibiotic therapy against PJIs. In particular, the oral-only linezolid-rifampin option might reduce venous access complications and health-care costs.
[Mh] Termos MeSH primário: Antibacterianos/uso terapêutico
Linezolida/uso terapêutico
Infecções Relacionadas à Prótese/tratamento farmacológico
Rifampina/uso terapêutico
Infecções Estafilocócicas/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Oral
Animais
Antibacterianos/administração & dosagem
Cefalosporinas/administração & dosagem
Cefalosporinas/uso terapêutico
Daptomicina/administração & dosagem
Daptomicina/uso terapêutico
Modelos Animais de Doenças
Doxiciclina/administração & dosagem
Doxiciclina/uso terapêutico
Combinação de Medicamentos
Linezolida/administração & dosagem
Staphylococcus aureus Resistente à Meticilina
Camundongos
Rifampina/administração & dosagem
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Cephalosporins); 0 (Drug Combinations); 0 (T 91825); ISQ9I6J12J (Linezolid); N12000U13O (Doxycycline); NWQ5N31VKK (Daptomycin); VJT6J7R4TR (Rifampin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170428
[Lr] Data última revisão:
170428
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.2106/JBJS.16.01002



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