The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice.

The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice.

BackgroundThe methicillin-resistant Staphylococcus aureus clone USA300 contains a novel mobile genetic element, arginine catabolic mobile element (ACME), that contributes to its enhanced capacity to grow and survive within the host. Although ACME appears to have been transferred into USA300 from S. epidermidis, the genetic diversity of ACME in the latter species remains poorly characterized.Methodology/Principal FindingsTo assess the prevalence and genetic diversity of ACME, 127 geographically diverse S. epidermidis isolates representing 86 different multilocus sequence types (STs) were characterized. ACME was found in 51% (65/127) of S. epidermidis isolates. The vast majority (57/65) of ACME-containing isolates belonged to the predominant S. epidermidis clonal complex CC2. ACME was often found in association with different allotypes of staphylococcal chromosome cassette mec (SCCmec) which also encodes the recombinase function that facilities mobilization ACME from the S. epidermidis chromosome. Restriction fragment length polymorphism, PCR scanning and DNA sequencing allowed for identification of 39 distinct ACME genetic variants that differ from one another in gene content, thereby revealing a hitherto uncharacterized genetic diversity within ACME. All but one ACME variants were represented by a single S. epidermidis isolate; the singular variant, termed ACME-I.02, was found in 27 isolates, all of which belonged to the CC2 lineage. An evolutionary model constructed based on the eBURST algorithm revealed that ACME-I.02 was acquired at least on 15 different occasions by strains belonging to the CC2 lineage.Conclusions/SignificanceACME-I.02 in diverse S. epidermidis isolates were nearly identical in sequence to the prototypical ACME found in USA300 MRSA clone, providing further evidence for the interspecies transfer of ACME from S. epidermidis into USA300.

Self-perpetuating photograft copolymerization based on the photochemistry of an iniferter benzyl N,N-diethyldithiocarbamate was utilized to design two types of microprocessed surfaces using a custom-designed apparatus operated by an X−Y step motor. Cellular adhesion and growth responses were studied on (1) a surface upon which five different water soluble polymer regions were photografted with micron order precision and (2) three different gradient surfaces with unidirectionally varying thicknesses of a water soluble graft polymer layer. A striped micropatterned surface (width of each region 500 μm) was prepared by sequential photoirradiation through a photomask with a stripe window on a selected region of a poly(styrene-co-vinylbenzyl N,N-diethyldithiocarbamate)-coated PET film immersed in an aqueous solution of vinyl monomer. The sample stage was moved in a stepwise manner for each change of monomer solution. The monomers studied were N,N-dimethylacrylamide (DMAAm), 2-hydroxyethyl methacrylate (HEMA), N-[3-(dimethylamino)propyl]acrylamide methiodide (DMAPAAmMeI), methacrylic acid sodium salt (MANa), and 3-sulfopropyl methacrylate potassium salt (SMAK). Surface wettability, X-ray photoelectron spectroscopic analyses, and light microscopic visualization by dye staining revealed that five stripe regions, each of which was grafted with a different polymer, were prepared side by side. Seeding and culture of endothelial cells (ECs) on the micropatterned surfaces yielded markedly reduced adhesion on polyDMAAm and polyHEMA. PolyDMAPAAmMeI and polyMANa regions promoted cell adhesion and growth, whereas enhanced adhesion was initially observed but then became markedly reduced over time on polySMAK. Atomic force microscopic (AFM) observation showed that photoirradiation through a photomask in the presence of a monomer solution (DMAAm, DMAPAAmMeI, and MANa) under continuous sample movement yielded a graft-polymer-layer thickness gradient surface. EC adhesion and proliferation gradually decreased with increasing graft layer thickness on the polyDMAPAAmMeI and polyMANa surfaces. In contrast, cell adhesion on the polyDMAAm-grafted surface ceased abruptly above a certain graft thickness. This study shows that, using this photograft copolymerization method, both regional and chemical specific surface modification on the micron level has been achieved, representing a significant advance in the microprocessing of biomedical devices.