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antimicrobial agents

  • Heterologous Expression of <em>ethA</em> and <em>katG</em> in <span class="named-content genus-species" id="named-content-1">Mycobacterium marinum</span> Enables the Rapid Identification of New Prodrugs Active against <span class="named-content genus-species" id="named-content-2">Mycobacterium tuberculosis</span>
    Susceptibility
    Heterologous Expression of ethA and katG in Mycobacterium marinum Enables the Rapid Identification of New Prodrugs Active against Mycobacterium tuberculosis

    Screening strategies for antituberculosis compounds using Mycobacterium tuberculosis are time consuming and require biosafety level 3 (BSL3) facilities, which makes the development of high-throughput assays difficult and expensive. Mycobacterium marinum, a close genetic relative of...

    Vien Q. T. Ho, Theo Verboom, Mark K. Rong, Eva Habjan, Wilbert Bitter, Alexander Speer
  • Open Access
    An Exposure-Response Perspective on the Clinical Dose of Pretomanid
    Clinical Therapeutics
    An Exposure-Response Perspective on the Clinical Dose of Pretomanid

    Pretomanid was approved by the U.S. FDA, via the limited population pathway for antibacterial and antifungal drugs, as part of a three-drug regimen with bedaquiline and linezolid for the treatment of extensively drug-resistant and treatment-intolerant or nonresponsive multidrug-resistant tuberculosis. The recommended dose of pretomanid is 200 mg once daily with food. The objective of this work was to retrospectively evaluate this...

    Jerry R. Nedelman, David H. Salinger, Vishak Subramoney, Rob Woolson, Karen Wade, Mengchun Li, Daniel Everitt, Carl M. Mendel, Mel Spigelman
  • Pharmacodynamics of the Novel Metallo-β-Lactamase Inhibitor ANT2681 in Combination with Meropenem for the Treatment of Infections Caused by NDM-Producing <em>Enterobacteriaceae</em>
    Pharmacology
    Pharmacodynamics of the Novel Metallo-β-Lactamase Inhibitor ANT2681 in Combination with Meropenem for the Treatment of Infections Caused by NDM-Producing Enterobacteriaceae

    Enterobacteriaceae that produce metallo-β-lactamases (MBLs) are an emerging threat to public health. The metallo-β-lactamase inhibitor (MBLi) ANT2681 inhibits the enzymatic activity of MBLs through interaction with the dinuclear zinc ion cluster present in the active site that is common to these enzymes. ANT2681 is being codeveloped, with meropenem as the partner β-lactam, as a novel combination therapy for infections caused by...

    Shampa Das, Adam Johnson, Laura McEntee, Nicola Farrington, Adam Kirby, Jennifer Unsworth, Ana Jimenez-Valverde, Ruwanthi Kolamunnage-Dona, Justine Bousquet, Laethitia Alibaud, Carole Sable, Magdalena Zalacain, Martin Everett, William Hope
  • Structural Recognition of Spectinomycin by Resistance Enzyme ANT(9) from <span class="named-content genus-species" id="named-content-1">Enterococcus faecalis</span>
    Editor's Pick Mechanisms of Resistance
    Structural Recognition of Spectinomycin by Resistance Enzyme ANT(9) from Enterococcus faecalis

    Spectinomycin is a ribosome-binding antibiotic that blocks the translocation step of translation. A prevalent resistance mechanism is modification of the drug by aminoglycoside nucleotidyl transferase (ANT) enzymes of the spectinomycin-specific ANT(9) family or by enzymes of the dual-specificity ANT(3ʺ)(9) family, which also acts on streptomycin. We previously reported the structural mechanism of streptomycin modification by the ANT(3ʺ...

    Sandesh Kanchugal P, Maria Selmer
  • Minocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective <em>In Vitro</em> for Eradication of <span class="named-content genus-species" id="named-content-1">Candida auris</span> Biofilms
    Experimental Therapeutics
    Minocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective In Vitro for Eradication of Candida auris Biofilms

    Candida auris is an emerging pathogen that can cause virulent central-line-associated bloodstream infections. Catheter salvage through the eradication of biofilms is a desirable therapeutic option. We compared taurolidine and minocycline-EDTA-ethanol (MEE) catheter lock solutions in vitro for the eradication of biofilms of 10...

    Ruth A. Reitzel, Joel Rosenblatt, Bahgat Z. Gerges, Nylev Vargas-Cruz, Issam I. Raad
  • Retrospective Analysis of Antimicrobial Susceptibility Profiles of <em>Nocardia</em> Species from a Tertiary Hospital and Reference Laboratory, 2011 to 2017
    Susceptibility
    Retrospective Analysis of Antimicrobial Susceptibility Profiles of Nocardia Species from a Tertiary Hospital and Reference Laboratory, 2011 to 2017

    Nocardia species are found worldwide and are opportunistic pathogens of both immunocompromised and immunocompetent hosts. Recent updates to the taxonomy of this genus have indicated that there are more than 90 recognized species of Nocardia with 54 species reported to be clinically relevant.

    Ahmed M. Hamdi, Madiha Fida, Sharon M. Deml, Omar M. Abu Saleh, Nancy L. Wengenack
  • Fact versus Fiction: a Review of the Evidence behind Alcohol and Antibiotic Interactions
    Minireview
    Fact versus Fiction: a Review of the Evidence behind Alcohol and Antibiotic Interactions

    Many antibiotics carry caution stickers that warn against alcohol consumption. Data regarding concurrent use are sparse. An awareness of data that address this common clinical scenario is important so health care professionals can make informed clinical decisions and address questions in an evidence-based manner. The purpose of this systematic review was to determine the evidence behind alcohol warnings issued for many common...

    Kari A. Mergenhagen, Bethany A. Wattengel, Megan K. Skelly, Collin M. Clark, Thomas A. Russo
  • A Whole-Cell Screen Identifies Small Bioactives That Synergize with Polymyxin and Exhibit Antimicrobial Activities against Multidrug-Resistant Bacteria
    Susceptibility
    A Whole-Cell Screen Identifies Small Bioactives That Synergize with Polymyxin and Exhibit Antimicrobial Activities against Multidrug-Resistant Bacteria

    The threat of diminished antibiotic discovery has global health care in crisis. In the United States, it is estimated each year that over 2 million bacterial infections are resistant to first-line antibiotic treatments and cost in excess of 20 billion dollars.

    Shawn M. Zimmerman, Audrey-Ann J. Lafontaine, Carmen M. Herrera, Amanda B. Mclean, M. Stephen Trent
  • Population Pharmacokinetics and Pharmacogenetics of Ethambutol in Adult Patients Coinfected with Tuberculosis and HIV
    Clinical Therapeutics
    Population Pharmacokinetics and Pharmacogenetics of Ethambutol in Adult Patients Coinfected with Tuberculosis and HIV

    This study aimed to characterize the population pharmacokinetics and pharmacogenetics of ethambutol in tuberculosis-HIV-coinfected adult patients. Ethambutol plasma concentrations, determined by liquid chromatography-tandem mass spectrometry, in 63 patients receiving ethambutol as part of rifampin-based fixed-dose combination therapy for tuberculosis were analyzed using nonlinear mixed-effects modeling.

    Jesper Sundell, Emile Bienvenu, Sofia Birgersson, Angela Äbelö, Michael Ashton
  • Safety, Tolerability, and Pharmacokinetics of Oral Nafithromycin (WCK 4873) after Single or Multiple Doses and Effects of Food on Single-Dose Bioavailability in Healthy Adult Subjects
    Pharmacology
    Safety, Tolerability, and Pharmacokinetics of Oral Nafithromycin (WCK 4873) after Single or Multiple Doses and Effects of Food on Single-Dose Bioavailability in Healthy Adult Subjects

    Nafithromycin (WCK 4873), a novel lactone-ketolide, was administered to healthy adult subjects in 2 randomized, double-blind, placebo-controlled, phase 1 studies. In the first-in-human study, single ascending oral doses of nafithromycin (100 to 1,200 mg) were administered to subjects under fasted or fed conditions, with effects of food on bioavailability of nafithromycin studied at the dose levels of 400 and 800 mg.

    Piotr Iwanowski, Ashima Bhatia, Mugdha Gupta, Anasuya Patel, Rajesh Chavan, Ravindra Yeole, David Friedland

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