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1.
J Clin Microbiol ; 56(2)2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29118174

RESUMO

The FDA-CDC Antimicrobial Resistance Isolate Bank was created in July 2015 as a publicly available resource to combat antimicrobial resistance. It is a curated repository of bacterial isolates with an assortment of clinically important resistance mechanisms that have been phenotypically and genotypically characterized. In the first 2 years of operation, the bank offered 14 panels comprising 496 unique isolates and had filled 486 orders from 394 institutions throughout the United States. New panels are being added.


Assuntos
Bactérias/isolamento & purificação , Bancos de Espécimes Biológicos , Resistência Microbiana a Medicamentos , Fungos/isolamento & purificação , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/genética , Bancos de Espécimes Biológicos/organização & administração , Bancos de Espécimes Biológicos/normas , Centers for Disease Control and Prevention, U.S. , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/microbiologia , Fungos/efeitos dos fármacos , Fungos/genética , Humanos , Estados Unidos , United States Food and Drug Administration
3.
Microbiol Spectr ; 10(1): e0156421, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35019677

RESUMO

The emergence of SARS-CoV-2 created a crucial need for serology assays to detect anti-SARS-CoV-2 antibodies, which led to many serology assays entering the market. A trans-government collaboration was created in April 2020 to independently evaluate the performance of commercial SARS-CoV-2 serology assays and help inform U.S. Food and Drug Administration (FDA) regulatory decisions. To assess assay performance, three evaluation panels with similar antibody titer distributions were assembled. Each panel consisted of 110 samples with positive (n = 30) serum samples with a wide range of anti-SARS-CoV-2 antibody titers and negative (n = 80) plasma and/or serum samples that were collected before the start of the COVID-19 pandemic. Each sample was characterized for anti-SARS-CoV-2 antibodies against the spike protein using enzyme-linked immunosorbent assays (ELISA). Samples were selected for the panel when there was agreement on seropositivity by laboratories at National Cancer Institute's Frederick National Laboratory for Cancer Research (NCI-FNLCR) and Centers for Disease Control and Prevention (CDC). The sensitivity and specificity of each assay were assessed to determine Emergency Use Authorization (EUA) suitability. As of January 8, 2021, results from 91 evaluations were made publicly available (https://open.fda.gov/apis/device/covid19serology/, and https://www.cdc.gov/coronavirus/2019-ncov/covid-data/serology-surveillance/serology-test-evaluation.html). Sensitivity ranged from 27% to 100% for IgG (n = 81), from 10% to 100% for IgM (n = 74), and from 73% to 100% for total or pan-immunoglobulins (n = 5). The combined specificity ranged from 58% to 100% (n = 91). Approximately one-third (n = 27) of the assays evaluated are now authorized by FDA for emergency use. This collaboration established a framework for assay performance evaluation that could be used for future outbreaks and could serve as a model for other technologies. IMPORTANCE The SARS-CoV-2 pandemic created a crucial need for accurate serology assays to evaluate seroprevalence and antiviral immune responses. The initial flood of serology assays entering the market with inadequate performance emphasized the need for independent evaluation of commercial SARS-CoV-2 antibody assays using performance evaluation panels to determine suitability for use under EUA. Through a government-wide collaborative network, 91 commercial SARS-CoV-2 serology assay evaluations were performed. Three evaluation panels with similar overall antibody titer distributions were assembled to evaluate performance. Nearly one-third of the assays evaluated met acceptable performance recommendations, and two assays had EUAs revoked and were removed from the U.S. market based on inadequate performance. Data for all serology assays evaluated are available at the FDA and CDC websites (https://open.fda.gov/apis/device/covid19serology/, and https://www.cdc.gov/coronavirus/2019-ncov/covid-data/serology-surveillance/serology-test-evaluation.html).


Assuntos
Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/sangue , Ensaio de Imunoadsorção Enzimática/métodos , SARS-CoV-2/imunologia , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Aprovação de Teste para Diagnóstico , Humanos , Laboratórios , Pandemias , SARS-CoV-2/genética , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/análise , Glicoproteína da Espícula de Coronavírus/imunologia , Estados Unidos/epidemiologia , United States Food and Drug Administration
4.
J Clin Microbiol ; 46(9): 2842-7, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18614654

RESUMO

Determining the genetic characteristics of Staphylococcus aureus is important for better understanding of the global and dynamic epidemiology of this organism as we witness the emergence and spread of virulent and antibiotic-resistant clones. We genotyped 292 S. aureus isolates (105 methicillin resistant and 187 methicillin susceptible) using a combination of pulsed-field gel electrophoresis, multilocus sequence typing, and SCCmec typing. In addition, S. aureus isolates were tested for the presence of the Panton-Valentine leukocidin (PVL) genes. Isolates were recovered from patients with uncomplicated skin infections in 10 different countries during five phase III global clinical trials of retapamulin, a new topical antibiotic agent. The most common methicillin-resistant clone had multilocus sequence type 8, pulsed-field type USA300, and SCCmec type IV and possessed the PVL genes. This clone was isolated exclusively in the United States. The most common PVL-positive, methicillin-susceptible clone had multilocus sequence type 121 and pulsed-field type USA1200. This clone was found primarily in South Africa and the Russian Federation. Other clones were found at lower frequencies and were limited in their geographic distribution. Overall, considerable genetic diversity was observed within multilocus sequence type clonal complexes and pulsed-field types.


Assuntos
Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus/genética , Humanos , Índia/epidemiologia , Resistência a Meticilina/genética , Epidemiologia Molecular , Pele/microbiologia , África do Sul/epidemiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia
5.
J Med Chem ; 47(19): 4693-709, 2004 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-15341485

RESUMO

A fluoroquinolone prodrug, PA2808, was prepared and shown to convert to the highly active parent drug PA2789. In vitro and in vivo activation of PA2808 by alkaline phosphatase was demonstrated using disk diffusion and rat lung infection models. The water solubility of PA2808 showed a marked increase compared to PA2789 over a pH range suitable for aerosol drug delivery. A total of 48 analogues based on PA2789 were prepared and screened against a panel of Gram-positive and Gram-negative pathogens. Incorporating a cyclopropane-fused pyrrolidine (amine) at C-7 resulted in some of the most active analogues.


Assuntos
Ácidos Carboxílicos/química , Fluoroquinolonas/química , Fluoroquinolonas/farmacologia , Pró-Fármacos/química , Água/química , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Fluoroquinolonas/síntese química , Fluoroquinolonas/farmacocinética , Pulmão/metabolismo , Estrutura Molecular , Ácido Nalidíxico/análogos & derivados , Ácido Nalidíxico/síntese química , Ácido Nalidíxico/química , Ácido Nalidíxico/metabolismo , Ácido Nalidíxico/farmacocinética , Ácido Nalidíxico/farmacologia , Organofosfatos/síntese química , Organofosfatos/química , Organofosfatos/farmacocinética , Organofosfatos/farmacologia , Piperazinas/química , Piperazinas/metabolismo , Piperazinas/farmacocinética , Piperazinas/farmacologia , Pró-Fármacos/síntese química , Pró-Fármacos/metabolismo , Pró-Fármacos/farmacocinética , Ratos , Solubilidade , Relação Estrutura-Atividade
6.
Expert Rev Anti Infect Ther ; 7(3): 269-79, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19344241

RESUMO

Retapamulin is a new topical pleuromutilin antibiotic for the treatment of skin and skin-structure infections, including impetigo. In vitro studies indicate that retapamulin has a unique mode of action that minimizes the potential for target-specific cross-resistance with other antibacterials and a limited potential for resistance development. Its spectrum of activity includes the most likely causative pathogens Staphylococcus aureus and Streptococcus pyogenes. In the Global Surveillance Program, retapamulin was highly active in vitro, including against strains of S. aureus resistant to methicillin, mupirocin or fusidic acid. In clinical studies, retapamulin was noninferior to fusidic acid and oral cefalexin, achieving per-pathogen success rates of 86-99%. Topical retapamulin has a good safety profile and is associated with high patient compliance.


Assuntos
Antibacterianos , Compostos Bicíclicos Heterocíclicos com Pontes , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologia , Administração Cutânea , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Diterpenos , Farmacorresistência Bacteriana , Saúde Global , Humanos , Testes de Sensibilidade Microbiana , Pomadas/administração & dosagem , Vigilância da População/métodos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/efeitos dos fármacos , Resultado do Tratamento
7.
J Infect Dis ; 197(2): 187-94, 2008 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-18177252

RESUMO

BACKGROUND: The majority of recent community-associated methicillin-resistant Staphylococcus aureus (MRSA) infections in the United States have been caused by a single clone, USA300. USA300 secretes Panton-Valentine leukocidin (PVL) toxin, which is associated with highly virulent infections. METHODS: We sequenced the PVL genes of 174 S. aureus isolates from a global clinical sample. We combined phylogenetic reconstruction and protein modeling methods to analyze genetic variation in PVL. RESULTS: Nucleotide variation was detected at 12 of 1726 sites. Two PVL sequence variants, the R variant and the H variant, were identified on the basis of a substitution at nt 527. Of sequences obtained in the United States, 96.7% harbor the R variant, whereas 95.6% of sequences obtained outside the United States harbor the H variant; 91.3% of MRSA isolates harbor the R variant, and 91.3% of methicillin-susceptible strains harbor the H variant. A molecular model of PVL shows 3 mechanisms by which the amino acid substitution may affect PVL function. CONCLUSIONS: All sampled PVL genes appear to share a recent common ancestor and spread via a combination of clonal expansion and horizontal transfer. US isolates harbor a variant of PVL that is strongly associated with MRSA infections. Protein modeling reveals that this variant may have functional significance. We propose a hypothesis for the origin of USA300.


Assuntos
Toxinas Bacterianas/genética , Infecções Comunitárias Adquiridas/microbiologia , Exotoxinas/genética , Variação Genética , Leucocidinas/genética , Resistência a Meticilina , Staphylococcus aureus/classificação , Adulto , Substituição de Aminoácidos , Toxinas Bacterianas/química , Criança , Pré-Escolar , Evolução Molecular , Exotoxinas/química , Transferência Genética Horizontal , Humanos , Leucocidinas/química , Meticilina/farmacologia , Modelos Moleculares , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNA , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética
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