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Methicillin-Resistant Staphylococcus aureus: HELP
Articles from San Francisco
Based on 69 articles published since 2009
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These are the 69 published articles about Methicillin-Resistant Staphylococcus aureus that originated from San Francisco during 2009-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. 2011

Liu, Catherine / Bayer, Arnold / Cosgrove, Sara E / Daum, Robert S / Fridkin, Scott K / Gorwitz, Rachel J / Kaplan, Sheldon L / Karchmer, Adolf W / Levine, Donald P / Murray, Barbara E / J Rybak, Michael / Talan, David A / Chambers, Henry F. ·Department of Medicine, Division of Infectious Diseases, University of California-San Francisco, San Francisco, California 94102, USA. catherine.liu@ucsf.edu ·Clin Infect Dis · Pubmed #21217178.

ABSTRACT: Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.

2 Guideline Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. 2011

Liu, Catherine / Bayer, Arnold / Cosgrove, Sara E / Daum, Robert S / Fridkin, Scott K / Gorwitz, Rachel J / Kaplan, Sheldon L / Karchmer, Adolf W / Levine, Donald P / Murray, Barbara E / J Rybak, Michael / Talan, David A / Chambers, Henry F / Anonymous770683. ·Department of Medicine, Division of Infectious Diseases, University of California-San Francisco, San Francisco, California94102, USA. catherine.liu@ucsf.edu ·Clin Infect Dis · Pubmed #21208910.

ABSTRACT: Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.

3 Review Cutaneous community-acquired and hospital-acquired methicillin-resistant Staphylococcus aureus. 2011

Hansra, Nina Kaur / Shinkai, Kanade. ·Department of Dermatology, University of California-San Francisco, 1701 Divisadero Street, San Francisco, CA 94143, USA. ·Dermatol Ther · Pubmed #21410616.

ABSTRACT: The clinical presentation of methicillin-resistant Staphylococcus aureus (MRSA) infection ranges from asymptomatic colonization to cutaneous and invasive involvement. This review discusses the cutaneous presentations of community-acquired MRSA (CA-MRSA) and hospital-acquired MRSA (HA-MRSA) that one may encounter in the hospital or outpatient setting. Cutaneous CA-MRSA and HA-MRSA are often clinically indistinguishable, although they have different epidemiologic profiles and virulence factors. Bacterial culture is necessary for diagnosis and guides treatment, as infection with CA-MRSA and HA-MRSA require distinct clinical management. Guidelines for surgical interventions and antibiotic treatment of CA-MRSA and HA-MRSA will be discussed. Strategies for MRSA decolonization and prevention of further spread will also be reviewed.

4 Clinical Trial Assessment of telavancin minimal inhibitory concentrations by revised broth microdilution method in phase 3 complicated skin and skin-structure infection clinical trial isolates. 2017

Smart, Jennifer I / Corey, G Ralph / Stryjewski, Martin E / Wang, Whedy / Barriere, Steven L. ·Theravance Biopharma US, Inc., South San Francisco, CA, USA. Electronic address: jsmart@smartmicrobiology.com. · Duke Clinical Research Institute and Duke University Medical Center, Durham, NC, USA. · Department of Medicine, Section of Infectious Diseases, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Buenos Aires, Argentina. · Theravance Biopharma US, Inc., South San Francisco, CA, USA. ·Diagn Microbiol Infect Dis · Pubmed #28038840.

ABSTRACT: The broth microdilution (BMD) MIC testing method for telavancin was recently revised BMD (rBMD) to improve accuracy and reproducibility. Staphylococcus aureus isolates from telavancin phase 3 complicated skin and skin-structure infection (cSSSI) studies were tested using the rBMD method. Retesting of 1132 isolates produced MICs ranging from ≤0.015 to 0.12μg/mL that were 8-fold lower than the original method. All isolates tested remained susceptible to telavancin at the revised susceptibility breakpoint of 0.12μg/mL. The clinical cure and microbiological eradication rates were 90% (368/409) and 89% (366/409) for telavancin-treated patients, and were similar for patients with methicillin-susceptible and -resistant S. aureus isolates and S. aureus isolates with elevated vancomycin MICs (≥1μg/mL). The data presented here are aimed to update the literature and better inform clinicians and clinical microbiologists about the revised telavancin MICs, as well as the corresponding clinical and microbiological cure rates for cSSSI patients.

5 Clinical Trial Novel staphylococcal glycosyltransferases SdgA and SdgB mediate immunogenicity and protection of virulence-associated cell wall proteins. 2013

Hazenbos, Wouter L W / Kajihara, Kimberly K / Vandlen, Richard / Morisaki, J Hiroshi / Lehar, Sophie M / Kwakkenbos, Mark J / Beaumont, Tim / Bakker, Arjen Q / Phung, Qui / Swem, Lee R / Ramakrishnan, Satish / Kim, Janice / Xu, Min / Shah, Ishita M / Diep, Binh An / Sai, Tao / Sebrell, Andrew / Khalfin, Yana / Oh, Angela / Koth, Chris / Lin, S Jack / Lee, Byoung-Chul / Strandh, Magnus / Koefoed, Klaus / Andersen, Peter S / Spits, Hergen / Brown, Eric J / Tan, Man-Wah / Mariathasan, Sanjeev. ·Dept. of Infectious Diseases, Genentech, Inc., San Francisco, California, United States of America. ·PLoS Pathog · Pubmed #24130480.

ABSTRACT: Infection of host tissues by Staphylococcus aureus and S. epidermidis requires an unusual family of staphylococcal adhesive proteins that contain long stretches of serine-aspartate dipeptide-repeats (SDR). The prototype member of this family is clumping factor A (ClfA), a key virulence factor that mediates adhesion to host tissues by binding to extracellular matrix proteins such as fibrinogen. However, the biological siginificance of the SDR-domain and its implication for pathogenesis remain poorly understood. Here, we identified two novel bacterial glycosyltransferases, SdgA and SdgB, which modify all SDR-proteins in these two bacterial species. Genetic and biochemical data demonstrated that these two glycosyltransferases directly bind and covalently link N-acetylglucosamine (GlcNAc) moieties to the SDR-domain in a step-wise manner, with SdgB appending the sugar residues proximal to the target Ser-Asp repeats, followed by additional modification by SdgA. GlcNAc-modification of SDR-proteins by SdgB creates an immunodominant epitope for highly opsonic human antibodies, which represent up to 1% of total human IgG. Deletion of these glycosyltransferases renders SDR-proteins vulnerable to proteolysis by human neutrophil-derived cathepsin G. Thus, SdgA and SdgB glycosylate staphylococcal SDR-proteins, which protects them against host proteolytic activity, and yet generates major eptopes for the human anti-staphylococcal antibody response, which may represent an ongoing competition between host and pathogen.

6 Clinical Trial ATLAS trials: efficacy and safety of telavancin compared with vancomycin for the treatment of skin infections. 2010

Barriere, Steven L. ·Theravance, Inc., 901 Gateway Boulevard, South San Francisco, CA 94080, USA. sbarriere@theravance.com ·Future Microbiol · Pubmed #21080861.

ABSTRACT: Telavancin is an injectable lipoglycopeptide that is bactericidal in vitro against staphylococci, streptococci and vancomycin-susceptible enterococci. Telavancin inhibits bacterial cell wall synthesis by interfering with the synthesis of peptidoglycan, and binds to the bacterial membrane and disrupts membrane barrier function. The Assessment of Telavancin in cSSSI (ATLAS) program, comprising of two Phase III clinical trials, demonstrated noninferiority of telavancin to vancomycin for the treatment of complicated skin and skin-structure infections including infections due to methicillin-resistant Staphylococcus aureus (MRSA). Among clinically evaluable patients with MRSA isolated at baseline in the pooled study population, the clinical cure rate was 87.0% (208 out of 239) for patients treated with telavancin and 85.9% (225 out of 262) for patients treated with vancomycin. The most common telavancin treatment-emergent adverse events were taste disturbance, nausea, vomiting and foamy urine. Renal adverse events occurred in 3% of telavancin-treated patients and 1% of vancomycin-treated patients. Telavancin is now approved in the USA and Canada for the treatment of Gram-positive complicated skin and skin-structure infections.

7 Clinical Trial In vitro activity of telavancin against Gram-positive isolates from complicated skin and skin structure infections: results from 2 phase 3 (ATLAS) clinical studies. 2010

Krause, Kevin M / Barriere, Steven L / Kitt, Michael M / Benton, Bret M. ·Theravance, Inc., South San Francisco, CA 94080, USA. ·Diagn Microbiol Infect Dis · Pubmed #20846593.

ABSTRACT: During phase 3 clinical studies of telavancin for treatment of complicated skin and skin structure infections, a total of 1530 aerobic Gram-positive isolates were identified at baseline. The majority of these strains were Staphylococcus aureus (n = 1214; 62% methicillin-resistant). All isolates were inhibited by ≤ 1 μg/mL of telavancin.

8 Article Structural investigation of human S. aureus-targeting antibodies that bind wall teichoic acid. 2018

Fong, Rina / Kajihara, Kimberly / Chen, Matthew / Hotzel, Isidro / Mariathasan, Sanjeev / Hazenbos, Wouter L W / Lupardus, Patrick J. ·a Department of Structural Biology , Genentech , South San Francisco , CA , USA. · b Departments of Infectious Diseases , Genentech , South San Francisco , CA , USA. · c Departments of Antibody Engineering , Genentech , South San Francisco , CA , USA. ·MAbs · Pubmed #30102105.

ABSTRACT: Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a growing health threat worldwide. Efforts to identify novel antibodies that target S. aureus cell surface antigens are a promising direction in the development of antibiotics that can halt MRSA infection. We biochemically and structurally characterized three patient-derived MRSA-targeting antibodies that bind to wall teichoic acid (WTA), which is a polyanionic surface glycopolymer. In S. aureus, WTA exists in both α- and β-forms, based on the stereochemistry of attachment of a N-acetylglucosamine residue to the repeating phosphoribitol sugar unit. We identified a panel of antibodies cloned from human patients that specifically recognize the α or β form of WTA, and can bind with high affinity to pathogenic wild-type strains of S. aureus bacteria. To investigate how the β-WTA specific antibodies interact with their target epitope, we determined the X-ray crystal structures of the three β-WTA specific antibodies, 4462, 4497, and 6078 (Protein Data Bank IDs 6DWI, 6DWA, and 6DW2, respectively), bound to a synthetic WTA epitope. These structures reveal that all three of these antibodies, while utilizing distinct antibody complementarity-determining region sequences and conformations to interact with β-WTA, fulfill two recognition principles: binding to the β-GlcNAc pyranose core and triangulation of WTA phosphate residues with polar contacts. These studies reveal the molecular basis for targeting a unique S. aureus cell surface epitope and highlight the power of human patient-based antibody discovery techniques for finding novel pathogen-targeting therapeutics.

9 Article None 2018

Jaganath, Devan / Jorakate, Possawat / Makprasert, Sirirat / Sangwichian, Ornuma / Akarachotpong, Thantapat / Thamthitiwat, Somsak / Khemla, Supphachoke / DeFries, Triveni / Baggett, Henry C / Whistler, Toni / Gregory, Christopher J / Rhodes, Julia. ·Division of Pediatric Infectious Diseases, Department of Pediatrics, University of California San Francisco, San Francisco, California. · Global Disease Detection Center, Thailand Ministry of Public Health (MOPH)-United States Centers for Disease Control and Prevention (CDC) Collaboration, Nonthaburi, Thailand. · Nakhon Phanom General Hospital, Nakhon Phanom, Thailand. · Division of Global Health Protection, Center for Global Health, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia. ·Am J Trop Med Hyg · Pubmed #29761760.

ABSTRACT:

10 Article Demographic fluctuation of community-acquired antibiotic-resistant Staphylococcus aureus lineages: potential role of flimsy antibiotic exposure. 2018

Gustave, Claude-Alexandre / Tristan, Anne / Martins-Simões, Patricia / Stegger, Marc / Benito, Yvonne / Andersen, Paal Skytt / Bes, Michèle / Le Hir, Typhanie / Diep, Binh An / Uhlemann, Anne-Catrin / Glaser, Philippe / Laurent, Frédéric / Wirth, Thierry / Vandenesch, François. ·CIRI - Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, F-69007, Lyon, France. · Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France. · Department for Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark. · Department of Veterinary and Animal Sciences, Frederiksberg, Denmark. · Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, CA, USA. · Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York City, NY, USA. · Institut Pasteur - APHP - Université Paris Sud, Unité Ecologie et Evolution de la Résistance aux Antibiotiques Paris, France, CNRS UMR3525, Paris, France. · Institut de Systématique, Evolution, Biodiversité (ISYEB - UMR 7205, CNRS, MNHN, UPMC, EPHE), Muséum National d'Histoire Naturelle, Sorbonne Universités, Paris, France. · EPHE, PSL University, Paris, France. · CIRI - Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, F-69007, Lyon, France. francois.vandenesch@univ-lyon1.fr. · Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France. francois.vandenesch@univ-lyon1.fr. ·ISME J · Pubmed #29599521.

ABSTRACT: Community-acquired (CA)- as opposed to hospital acquired- methicillin-resistant Staphylococcus aureus (MRSA) lineages arose worldwide during the 1990s. To determine which factors, including selective antibiotic pressure, govern the expansion of two major lineages of CA-MRSA, namely "USA300" in Northern America and "European ST80" in North Africa, Europe and Middle-East, we explored virulence factor expression, and fitness levels with or without antibiotics. The sampled strains were collected in a temporal window representing various steps of the epidemics, reflecting predicted changes in effective population size as inferred from whole-genome analysis. In addition to slight variations in virulence factor expression and biofilm production that might influence the ecological niches of theses lineages, competitive fitness experiments revealed that the biological cost of resistance to methicillin, fusidic acid and fluoroquinolones is totally reversed in the presence of trace amount of antibiotics. Our results suggest that low-level antibiotics exposure in human and animal environments contributed to the expansion of both European ST80 and USA300 lineages in community settings. This surge was likely driven by antibiotic (ab)use promoting the accumulation of antibiotics as environmental pollutants. The current results provide a novel link between effective population size increase of a pathogen and a selective advantage conferred by antibiotic resistance.

11 Article Effective Antimicrobial Stewardship Strategies for Cost-effective Utilization of Telavancin for the Treatment of Patients With Hospital-acquired Bacterial Pneumonia Caused by Staphylococcus aureus. 2018

McKinnell, James A / Corman, Shelby / Patel, Dipen / Leung, Grace H / Gordon, Lynne M / Lodise, Thomas P. ·Infectious Disease Clinical Outcomes Research Unit (ID-CORE), Division of Infectious Disease, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California. Electronic address: dr.mckinnell@yahoo.com. · Pharmerit International, Bethesda, Maryland. · Theravance Biopharma US, Inc, South San Francisco, California. · Albany College of Pharmacy and Health Sciences, Albany, Maryland. ·Clin Ther · Pubmed #29454592.

ABSTRACT: PURPOSE: Clinicians and stewardship programs are challenged with positioning of novel, higher priced antibiotic agents for the treatment of clinical infections. We developed a decision-analytic model to describe costs, including drug, total treatment costs, and health care outcomes, associated with telavancin (TLV) compared with vancomycin (VAN) for patients with Staphylococcus aureus (SA) hospital-acquired bacterial pneumonia (HABP). METHODS: This decision-analytic model assessed the treatment of SA-HABP with TLV versus VAN. Data were obtained from the ATTAIN (Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia) clinical trials on the following: the probability of clinical cure; probability of nephrotoxicity; and prevalence of polymicrobial infection (30%), methicillin-resistant Staphylococcus aureus (MRSA) (68%), and SA with VAN MIC ≥1 µg/mL (85%). Data on length of stay for cure (10 days), failure (10 additional days), and nephrotoxicity (3.5 days) were based on literature. Cost per treated patient and incremental cost-effectiveness ratio (ICER) per additional cure were calculated for SA-HABP and for monomicrobial SA-HABP. One-way sensitivity analyses were performed. FINDINGS: Patients with SA-HABP were sub-grouped by methicillin susceptibility (n = 140, 32%) or resistance (n = 293, 68%), and occurrence of polymicrobial (n = 128, 30%) vs monomicrobial (n = 305, 70%) infections. Under the base case, hospital cost for patients with HABP treated with TLV was $42,564 and with VAN, it was $42,296. Telavancin was associated with higher drug ($2082) and nephrotoxicity ($467) costs and lower intensive care unit (-$1738) and ventilator (-$114) costs. ICER was $4156 per additional cure. ICER was sensitive to probabilities of cure, length of treatment in cures, intensive care unit cost, TLV cost, and additional length of stay due to failure. For monomicrobial SA-HABP, TLV was associated with a net cost savings of $907 per patient and yielded economic dominance. IMPLICATIONS: Our decision-analytic model suggests that TLV for monomicrobial SA-HABP is associated with higher drug acquisition costs but a favorable ICER relative to VAN, provided that effective antimicrobial stewardship limits therapy to 7 days. Sensitivity analyses suggest a potential economic benefit of TLV treatment with appropriate patient selection. Antimicrobial stewardship programs may be able to reduce total costs through judicious use of novel antimicrobial agents. ClinicalTrials.gov identifiers: NCT00107952 and NCT00124020.

12 Article Staphylococcus aureus SaeR/S-Regulated Factors Decrease Monocyte-Derived Tumor Necrosis Factor-α to Reduce Neutrophil Bactericidal Activity. 2018

Sward, Eli W / Fones, Elizabeth M / Spaan, Russel R / Pallister, Kyler B / Haller, Brandon L / Guerra, Fermin E / Zurek, Oliwia W / Nygaard, Tyler K / Voyich, Jovanka M. ·Department of Microbiology and Immunology, Montana State University, Bozeman. · Infectious Disease Department, Genentech Inc, South San Francisco, California. ·J Infect Dis · Pubmed #29272502.

ABSTRACT: Background: The ability of Staphylococcus aureus to evade killing by human neutrophils significantly contributes to disease progression. In this study, we characterize an influential role for the S. aureus SaeR/S 2-component gene regulatory system in suppressing monocyte production of tumor necrosis factor alpha (TNF-α) to subsequently influence human neutrophil priming. Methods: Using flow cytometry and TNF-α specific enzyme-linked immunosorbent assays we identify the primary cellular source of TNF-α in human blood and in purified peripheral blood mononuclear cells (PBMCs) during interaction with USA300 and an isogenic saeR/S deletion mutant (USA300∆saeR/S). Assays with conditioned media from USA300 and USA300∆saeR/S exposed PBMCs were used to investigate priming on neutrophil bactericidal activity. Results: TNF-α production from monocytes was significantly reduced following challenge with USA300 compared to USA300∆saeR/S. We observed that priming of neutrophils using conditioned medium from peripheral blood mononuclear cells stimulated with USA300∆saeR/S significantly increased neutrophil bactericidal activity against USA300 relative to unprimed neutrophils and neutrophils primed with USA300 conditioned medium. The increased neutrophil bactericidal activity was associated with enhanced reactive oxygen species production that was significantly influenced by elevated TNF-α concentrations. Conclusions: Our findings identify an immune evasion strategy used by S. aureus to impede neutrophil priming and subsequent bactericidal activity.

13 Article Identification of Vancomycin Exposure-Toxicity Thresholds in Hospitalized Patients Receiving Intravenous Vancomycin. 2018

Zasowski, Evan J / Murray, Kyle P / Trinh, Trang D / Finch, Natalie A / Pogue, Jason M / Mynatt, Ryan P / Rybak, Michael J. ·Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA. · Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA. · Department of Pharmacy Services, Huron Valley Sinai Hospital, Commerce Charter Township, Michigan, USA. · Department of Clinical Pharmacy, UCSF School of Pharmacy, San Francisco, California, USA. · Department of Pharmacy Services, Detroit Receiving Hospital, Detroit, Michigan, USA. · Department of Pharmacy Services, Sinai-Grace Hospital, Detroit, Michigan, USA. · Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA m.rybak@wayne.edu. · Department of Medicine, Division of Infectious Diseases, School of Medicine, Wayne State University, Detroit, Michigan, USA. ·Antimicrob Agents Chemother · Pubmed #29084753.

ABSTRACT: Evidence supports vancomycin therapeutic-drug monitoring by area under the concentration-time curve (AUC), but data to establish an AUC upper limit are limited and published nephrotoxicity thresholds range widely. The objective of this analysis was to examine the association between initial vancomycin AUC and nephrotoxicity. This was a multicenter, retrospective cohort study of adult patients receiving intravenous vancomycin from 2014 to 2015. Nephrotoxicity was defined as a serum creatinine increase of 0.5 mg/liter and 50% from baseline on consecutive measurements. Vancomycin exposure profile during the initial 48 h of therapy was estimated using maximum

14 Article Prevalence of Slow-Growth Vancomycin Nonsusceptibility in Methicillin-Resistant Staphylococcus aureus. 2017

Katayama, Yuki / Azechi, Takuya / Miyazaki, Motoyasu / Takata, Tohru / Sekine, Miwa / Matsui, Hidehito / Hanaki, Hideaki / Yahara, Koji / Sasano, Hiroshi / Asakura, Kota / Takaku, Tomoiku / Ochiai, Tomonori / Komatsu, Norio / Chambers, Henry F. ·Department of Microbiology, Faculty of Medicine, Juntendo University, Tokyo, Japan yukk@juntendo.ac.jp. · Department of Pharmacy, Juntendo University Hospital, Tokyo, Japan. · Department of Pharmacy, Fukuoka University Chikushi Hospital, Chikushino, Japan. · Department of Infection Control, Fukuoka University Hospital, Fukuoka, Japan. · Department of Microbiology, Faculty of Medicine, Juntendo University, Tokyo, Japan. · Infection Control Research Center, Kitasato Institute for Life Science, Kitasato University, Tokyo, Japan. · Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan. · Division of Hematology, Department of Internal Medicine, Juntendo University, Tokyo, Japan. · Department of Medicine, University of California San Francisco, San Francisco, California, USA. ·Antimicrob Agents Chemother · Pubmed #28827421.

ABSTRACT: We previously reported a novel phenotype of vancomycin-intermediate

15 Article A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses. 2017

Daum, Robert S / Miller, Loren G / Immergluck, Lilly / Fritz, Stephanie / Creech, C Buddy / Young, David / Kumar, Neha / Downing, Michele / Pettibone, Stephanie / Hoagland, Rebecca / Eells, Samantha J / Boyle, Mary G / Parker, Trisha Chan / Chambers, Henry F / Anonymous511322. ·From the University of Chicago Hospitals, Chicago (R.S.D., N.K.) · Harbor-UCLA Medical Center and Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Los Angeles (L.G.M., S.J.E.), and University of California, San Francisco-San Francisco General Hospital, San Francisco (D.Y., M.D., H.F.C.) · Morehouse School of Medicine and Emory University-Grady Memorial Hospital and Children's Healthcare of Atlanta, Atlanta (L.I., T.C.P.) · Washington University School of Medicine-Barnes-Jewish Hospital and St. Louis Children's Hospital, St. Louis (S.F., M.G.B.) · Vanderbilt University School of Medicine and Vanderbilt University Medical Center, Nashville (C.B.C.) · EMMES Corporation, Rockville, MD (S.P.) · and Cota Enterprises, Meriden, KS (R.H.). ·N Engl J Med · Pubmed #28657870.

ABSTRACT: BACKGROUND: Uncomplicated skin abscesses are common, yet the appropriate management of the condition in the era of community-associated methicillin-resistant Staphylococcus aureus (MRSA) is unclear. METHODS: We conducted a multicenter, prospective, double-blind trial involving outpatient adults and children. Patients were stratified according to the presence of a surgically drainable abscess, abscess size, the number of sites of skin infection, and the presence of nonpurulent cellulitis. Participants with a skin abscess 5 cm or smaller in diameter were enrolled. After abscess incision and drainage, participants were randomly assigned to receive clindamycin, trimethoprim-sulfamethoxazole (TMP-SMX), or placebo for 10 days. The primary outcome was clinical cure 7 to 10 days after the end of treatment. RESULTS: We enrolled 786 participants: 505 (64.2%) were adults and 281 (35.8%) were children. A total of 448 (57.0%) of the participants were male. S. aureus was isolated from 527 participants (67.0%), and MRSA was isolated from 388 (49.4%). Ten days after therapy in the intention-to-treat population, the cure rate among participants in the clindamycin group was similar to that in the TMP-SMX group (221 of 266 participants [83.1%] and 215 of 263 participants [81.7%], respectively; P=0.73), and the cure rate in each active-treatment group was higher than that in the placebo group (177 of 257 participants [68.9%], P<0.001 for both comparisons). The results in the population of patients who could be evaluated were similar. This beneficial effect was restricted to participants with S. aureus infection. Among the participants who were initially cured, new infections at 1 month of follow-up were less common in the clindamycin group (15 of 221, 6.8%) than in the TMP-SMX group (29 of 215 [13.5%], P=0.03) or the placebo group (22 of 177 [12.4%], P=0.06). Adverse events were more frequent with clindamycin (58 of 265 [21.9%]) than with TMP-SMX (29 of 261 [11.1%]) or placebo (32 of 255 [12.5%]); all adverse events resolved without sequelae. One participant who received TMP-SMX had a hypersensitivity reaction. CONCLUSIONS: As compared with incision and drainage alone, clindamycin or TMP-SMX in conjunction with incision and drainage improves short-term outcomes in patients who have a simple abscess. This benefit must be weighed against the known side-effect profile of these antimicrobials. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00730028 .).

16 Article Low yield of blood and wound cultures in patients with skin and soft-tissue infections. 2017

Torres, Jesus / Avalos, Nathaniel / Echols, Lamarr / Mongelluzzo, Jillian / Rodriguez, Robert M. ·Department of Emergency Medicine, University of California, San Francisco, CA, United States. · Department of Emergency Medicine, University of California, San Francisco, CA, United States. Electronic address: Robert.rodriguez@ucsf.edu. ·Am J Emerg Med · Pubmed #28592371.

ABSTRACT: BACKGROUND: Current guidelines recommend blood cultures in skin and soft-tissue infection (SSTI) patients only with signs of systemic toxicity and wound cultures for severe purulent infections. Our objectives were to determine: 1) blood and wound culture yields in patients admitted with SSTIs; 2) whether injection drug users (IDUs) and febrile patients had higher blood culture yields; and 3) whether blood and wound cultures grew organisms sensitive to typical SSTI empiric antibiotics. METHODS: We prospectively enrolled adult patients admitted from the ED with SSTIs at an urban hospital. We recorded patient characteristics, including IDU, comorbidities and temperatures, and followed admitted patients throughout their hospital course. RESULTS: Of 734 SSTI patients enrolled, 246 (33.5%) were admitted. Of 86 (35.0%) patients who had blood cultures, six had positive cultures (yield=7.0%; 95% confidence intervals [CIs] 3.2-14.4); 4 were methicillin sensitive Staphylococcus aureus (MSSA) and 2 were methicillin resistant (MRSA). Of 29 febrile patients, 1 had a positive culture (yield=3.5%; 95% CI 0.6-17.2). Of 101 admitted IDU patients, 46 (46%) received blood cultures, and 4 had positive cultures (yield=8.7%; 95% CI 3.4-20.3). Of 89 patients with purulent wounds, 44 (49.4%) patients had ED wound cultures. Thirteen had positive cultures (yield=29.6%; 95% CI 18.2-44.2%). Most were MRSA, MSSA, and group A Streptococcus species - all sensitive to Vancomycin. CONCLUSIONS: Febrile and IDU patients had low yields of blood cultures similar to yields in non-IDU and afebrile patients. All blood and wound culture species were adequately covered by currently recommended empiric antibiotic regimens.

17 Article Activity of telavancin against Gram-positive pathogens isolated from bone and joint infections in North American, Latin American, European and Asia-Pacific nations. 2017

Jones, Ronald N / Flamm, Robert K / Castanheira, Mariana / Sader, Helio S / Smart, Jennifer I / Mendes, Rodrigo E. ·JMI Laboratories, North Liberty, Iowa, US. · Theravance Biopharma US, Inc., South San Francisco, CA, US. · JMI Laboratories, North Liberty, Iowa, US. Electronic address: rodrigo-mendes@jmilabs.com. ·Diagn Microbiol Infect Dis · Pubmed #28377166.

ABSTRACT: Telavancin was tested against a worldwide collection of Gram-positive pathogens (967) isolated from bone and joint infections (BJI). Most BJI isolates were from the United States (US) (49.9%) followed by Europe (26.4%), Latin America (LATAM; 14.4%), and Asia-Pacific (APAC; 9.3%). Organisms were tested by broth microdilution susceptibility methods. S. aureus (66.4%; range of 48.9% in APAC to 71.2% in LATAM) was the most common pathogen and had a 35.7% methicillin resistance (MRSA) rate and telavancin MIC

18 Article Ceftaroline-Resistant, Daptomycin-Tolerant, and Heterogeneous Vancomycin-Intermediate Methicillin-Resistant Staphylococcus aureus Causing Infective Endocarditis. 2017

Nigo, Masayuki / Diaz, Lorena / Carvajal, Lina P / Tran, Truc T / Rios, Rafael / Panesso, Diana / Garavito, Juan D / Miller, William R / Wanger, Audrey / Weinstock, George / Munita, Jose M / Arias, Cesar A / Chambers, Henry F. ·Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical School at Houston, Houston, Texas, USA. · Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, Colombia. · Center for Antimicrobial Resistance and Microbial Genomics, University of Texas McGovern Medical School, Houston, Texas, USA. · Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, Texas, USA. · The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA. · Department of Medicine, Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile. · Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical School at Houston, Houston, Texas, USA cesar.arias@uth.tmc.edu henry.chambers@ucsf.edu. · Department of Medicine, Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital, University of California San Francisco, San Francisco, California, USA cesar.arias@uth.tmc.edu henry.chambers@ucsf.edu. ·Antimicrob Agents Chemother · Pubmed #28232309.

ABSTRACT: We report a case of infective endocarditis (IE) caused by ceftaroline-resistant, daptomycin-tolerant, and heterogeneous vancomycin-intermediate methicillin-resistant

19 Article Effects of Tedizolid Phosphate on Survival Outcomes and Suppression of Production of Staphylococcal Toxins in a Rabbit Model of Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia. 2017

Le, Vien T M / Le, Hoan N / Pinheiro, Marcos Gabriel / Hahn, Kenneth J / Dinh, Mary L / Larson, Kajal B / Flanagan, Shawn D / Badiou, Cedric / Lina, Gerard / Tkaczyk, Christine / Sellman, Bret R / Diep, Binh An. ·Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, California, USA. · Merck & Co., Inc., Kenilworth, New Jersey, USA. · INSERM U1111, Université Lyon 1, CNRS UMR5308, ENS Lyon, Lyon, France. · Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Bron, France. · Department of Infectious Diseases, MedImmune, Gaithersburg, Maryland, USA. · Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, California, USA binh.diep@ucsf.edu. ·Antimicrob Agents Chemother · Pubmed #28137816.

ABSTRACT: The protective efficacy of tedizolid phosphate, a novel oxazolidinone that potently inhibits bacterial protein synthesis, was compared to those of linezolid, vancomycin, and saline in a rabbit model of

20 Article Staphylococcus aureus nasal colonization among HIV-infected adults in Botswana: prevalence and risk factors. 2017

Reid, Michael J A / Steenhoff, Andrew P / Mannathoko, Naledi / Muthoga, Charles / McHugh, Erin / Brown, Eric L / Fischer, Rebecca S B. ·a Division of Infectious Diseases , University of California , San Francisco , USA. · b Botswana-UPenn Partnership , Gaborone , Botswana. · c Children's Hospital of Philadelphia, University of Pennsylvania , Philadelphia , USA. · d Faculty of Health Sciences, University of Botswana , Gaborone , Botswana. · e The University of Texas Health Science Center School of Public Health , Houston , Texas. · f National School of Tropical Medicine, Baylor College of Medicine , Houston , Texas. ·AIDS Care · Pubmed #28127988.

ABSTRACT: We sought to determine the clinical and epidemiologic determinants of Staphylococcus aureus nasal colonization in HIV-infected individuals at two outpatient centers in southern Botswana. Standard microbiologic techniques were used to identify S. aureus and methicillin-resistant S. aureus (MRSA). In a sample of 404 HIV-infected adults, prevalence of S. aureus nasal carriage was 36.9% (n = 152) and was associated with domestic overcrowding and lower CD4 cell count. MRSA prevalence was low (n = 13, 3.2%), but more common among individuals with asthma and eczema. The implications of these findings for HIV management are discussed.

21 Article Targeting Alpha Toxin To Mitigate Its Lethal Toxicity in Ferret and Rabbit Models of Staphylococcus aureus Necrotizing Pneumonia. 2017

Diep, Binh An / Hilliard, Jamese J / Le, Vien T M / Tkaczyk, Christine / Le, Hoan N / Tran, Vuvi G / Rao, Renee L / Dip, Etyene Castro / Pereira-Franchi, Eliane P / Cha, Paulyn / Jacobson, Scott / Broome, Rosemary / Cheng, Lily I / Weiss, William / Prokai, Laszlo / Nguyen, Vien / Stover, C Ken / Sellman, Bret R. ·Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, California, USA binh.diep@ucsf.edu sellmanb@medimmune.com. · Department of Infectious Diseases, MedImmune, LLC, Gaithersburg, Maryland, USA. · Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, California, USA. · Department of Applied Immunology and Microbiology, MedImmune, LLC, Mountain View, California, USA. · Department of Translational Sciences, MedImmune, LLC, Gaithersburg, Maryland, USA. · Pre-Clinical Services, University of North Texas Health Sciences Center, Fort Worth, Texas, USA. · Department of Infectious Diseases, MedImmune, LLC, Gaithersburg, Maryland, USA binh.diep@ucsf.edu sellmanb@medimmune.com. ·Antimicrob Agents Chemother · Pubmed #28115346.

ABSTRACT: The role broad-spectrum antibiotics play in the spread of antimicrobial resistance, coupled with their effect on the healthy microbiome, has led to advances in pathogen-specific approaches for the prevention or treatment of serious bacterial infections. One approach in clinical testing is passive immunization with a monoclonal antibody (MAb) targeting alpha toxin for the prevention or treatment of

22 Article Opioid and amphetamine dependence is associated with methicillin-resistant Staphylococcus aureus (MRSA): An epidemiological register study with 73,201 Swedish in- and outpatients 1997-2013. 2017

Dahlman, Disa / Berge, Jonas / Nilsson, Anna C / Kral, Alex H / Bjorkman, Per / Hakansson, Anders C. ·a Division of Psychiatry, Department of Clinical Sciences Lund , Lund University , Lund , Sweden. · b Malmo Addiction Centre , Malmo , Sweden. · c Infectious Disease Research Unit, Department of Translational Medicine , Lund University , Lund , Sweden. · d Behavioral and Urban Health Program , RTI International , San Francisco , CA , USA. ·Infect Dis (Lond) · Pubmed #27701936.

ABSTRACT: BACKGROUND: While methicillin-resistant Staphylococcus aureus (MRSA) is increasing in prevalence globally, Sweden is still a low-prevalence country enabling studies on the natural MRSA spread in subpopulations unaffected by a surrounding highly infected population. Substance dependence and injection drug use have been risk factors for MRSA carriage and infection in other countries. In this retrospective, longitudinal register study, we investigated MRSA epidemiology 1997-2013 in opioid and amphetamine-dependent individuals, in comparison with alcohol-dependent subjects. METHODS: Data from the national Swedish in- and outpatients registers included 73,201 individuals from 1997, 1999, 2004, 2009 and 2013. We analyzed substance use disorder and demographic predictors for MRSA using generalized estimating equations. RESULTS: The main finding was that both opioid (adjusted odds ratio [AOR] = 2.82; 95% confidence interval [CI] = 2.16, 3.67) and amphetamine dependence (AOR = 2.71; 95% CI = 1.70, 4.16) were significantly associated with MRSA diagnosis compared with alcohol dependence, when adjusting for age, sex and year. CONCLUSIONS: These findings are of value to understand the dynamics of MRSA epidemiology among substance dependent persons with presumably low socioeconomic status and potential injection drug use, and implicate repeated surveillance of MRSA among these patients.

23 Article IVIG-mediated protection against necrotizing pneumonia caused by MRSA. 2016

Diep, Binh An / Le, Vien T M / Badiou, Cedric / Le, Hoan N / Pinheiro, Marcos Gabriel / Duong, Au H / Wang, Xing / Dip, Etyene Castro / Aguiar-Alves, Fábio / Basuino, Li / Marbach, Helene / Mai, Thuy T / Sarda, Marie N / Kajikawa, Osamu / Matute-Bello, Gustavo / Tkaczyk, Christine / Rasigade, Jean-Philippe / Sellman, Bret R / Chambers, Henry F / Lina, Gerard. ·Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA. binh.diep@ucsf.edu gerard.lina@univ-lyon1.fr. · Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA. · INSERM U1111, Université Lyon 1, CNRS UMR5308, ENS Lyon, Lyon, France. Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Bron, France. · Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA. Pathology Program, Fluminense Federal University, Niterói, RJ, Brazil. · Laboratory of Immunology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, France. · Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA. · Department of Infectious Diseases, MedImmune, LLC, Gaithersburg, MD 20878, USA. · INSERM U1111, Université Lyon 1, CNRS UMR5308, ENS Lyon, Lyon, France. Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Bron, France. binh.diep@ucsf.edu gerard.lina@univ-lyon1.fr. ·Sci Transl Med · Pubmed #27655850.

ABSTRACT: New therapeutic approaches are urgently needed to improve survival outcomes for patients with necrotizing pneumonia caused by Staphylococcus aureus One such approach is adjunctive treatment with intravenous immunoglobulin (IVIG), but clinical practice guidelines offer conflicting recommendations. In a preclinical rabbit model, prophylaxis with IVIG conferred protection against necrotizing pneumonia caused by five different epidemic strains of community-associated methicillin-resistant S. aureus (MRSA) as well as a widespread strain of hospital-associated MRSA. Treatment with IVIG, either alone or in combination with vancomycin or linezolid, improved survival outcomes in this rabbit model. Two specific IVIG antibodies that neutralized the toxic effects of α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL) conferred protection against necrotizing pneumonia in the rabbit model. This mechanism of action of IVIG was uncovered by analyzing loss-of-function mutant bacterial strains containing deletions in 17 genes encoding staphylococcal exotoxins, which revealed only Hla and PVL as having an impact on necrotizing pneumonia. These results demonstrate the potential clinical utility of IVIG in the treatment of severe pneumonia induced by S. aureus.

24 Article Antibiotic safety considerations in methicillin-resistant Staphylococcus aureus postpartum mastitis. 2016

Farahnik, Benjamin / Murase, Jenny E. ·University of Vermont College of Medicine, Burlington, Vermont; Department of Dermatology, University of California, San Francisco, California. · Department of Dermatology, University of California, San Francisco, California; Department of Dermatology, Palo Alto Foundation Medical Group, Mountain View, California. Electronic address: jemurase@gmail.com. ·J Am Acad Dermatol · Pubmed #27646759.

ABSTRACT: -- No abstract --

25 Article Improved Protection in a Rabbit Model of Community-Associated Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia upon Neutralization of Leukocidins in Addition to Alpha-Hemolysin. 2016

Diep, Binh An / Le, Vien T M / Visram, Zehra C / Rouha, Harald / Stulik, Lukas / Dip, Etyene Castro / Nagy, Gábor / Nagy, Eszter. ·Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA binh.diep@ucsf.edu eszter.nagy@arsanis.com. · Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California, USA. · Arsanis, Inc./Arsanis Biosciences GmbH, Vienna, Austria. · Arsanis, Inc./Arsanis Biosciences GmbH, Vienna, Austria binh.diep@ucsf.edu eszter.nagy@arsanis.com. ·Antimicrob Agents Chemother · Pubmed #27527081.

ABSTRACT: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), especially the USA300 pulsotype, is a frequent cause of skin and soft tissue infections and severe pneumonia. Despite appropriate antibiotic treatment, complications are common and pneumonia is associated with high mortality. S. aureus strains express multiple cytotoxins, including alpha-hemolysin (Hla) and up to five bicomponent leukocidins that specifically target phagocytic cells for lysis. CA-MRSA USA300 strains carry the genes for all six cytotoxins. Species specificity of the leukocidins greatly contributes to the ambiguity regarding their role in S. aureus pathogenesis. We performed a comparative analysis of the leukocidin susceptibility of human, rabbit, and mouse polymorphonuclear leukocytes (PMNs) to assess the translational value of mouse and rabbit S. aureus models. We found that mouse PMNs were largely resistant to LukSF-PV, HlgAB, and HlgCB and susceptible only to LukED, whereas rabbit and human PMNs were highly sensitive to all these cytotoxins. In the rabbit pneumonia model with a USA300 CA-MRSA strain, passive immunization with a previously identified human monoclonal antibody (MAb), Hla-F#5, which cross-neutralizes Hla, LukSF-PV, HlgAB, HlgCB, and LukED, provided full protection, whereas an Hla-specific MAb was only partially protective. In the mouse USA300 CA-MRSA pneumonia model, both types of antibodies demonstrated full protection, suggesting that Hla, but not leukocidin(s), is the principal virulence determinant in mice. As the rabbit recapitulates the high susceptibility to leukocidins characteristic of humans, this species represents a valuable model for assessing novel, cytotoxin-targeting anti-S. aureus therapeutic approaches.

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