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aminoglycosides

  • A GC-Rich Prophage-Like Genomic Region of <span class="named-content genus-species" id="named-content-1">Mycoplasma bovirhinis</span> HAZ141_2 Carries a Gene Cluster Encoding Resistance to Kanamycin and Neomycin
    Mechanisms of Resistance
    A GC-Rich Prophage-Like Genomic Region of Mycoplasma bovirhinis HAZ141_2 Carries a Gene Cluster Encoding Resistance to Kanamycin and Neomycin

    Recently, a complete genome sequence of Mycoplasma bovirhinis HAZ141_2 was published showing the presence of a 54-kB prophage-like region. Bioinformatic analysis revealed that this region has a more than 40% GC content and a chimeric organization with three structural elements—a prophage continuous region, a restriction-modification cassette, and a highly...

    Inna Lysnyansky, Ilya Borovok
  • <span class="named-content genus-species" id="named-content-1">Pseudomonas aeruginosa</span> Polynucleotide Phosphorylase Controls Tolerance to Aminoglycoside Antibiotics by Regulating the MexXY Multidrug Efflux Pump
    Mechanisms of Resistance
    Pseudomonas aeruginosa Polynucleotide Phosphorylase Controls Tolerance to Aminoglycoside Antibiotics by Regulating the MexXY Multidrug Efflux Pump

    Pseudomonas aeruginosa is an opportunistic pathogen that shows high intrinsic resistance to a variety of antibiotics. The MexX-MexY-OprM efflux pump plays an important role in bacterial resistance to aminoglycoside antibiotics.

    Zheng Fan, Xiaolei Pan, Dan Wang, Ronghao Chen, Tongtong Fu, Baopeng Yang, Yongxin Jin, Fang Bai, Zhihui Cheng, Weihui Wu
  • A Systematic Review of Studies Reporting Antibiotic Pharmacokinetic Data in the Cerebrospinal Fluid of Critically Ill Patients with Uninflamed Meninges
    Clinical Therapeutics
    A Systematic Review of Studies Reporting Antibiotic Pharmacokinetic Data in the Cerebrospinal Fluid of Critically Ill Patients with Uninflamed Meninges

    Ventriculostomy-associated infections in critically ill patients remain therapeutically challenging because of drug- and disease-related factors that contribute to suboptimal antibiotic concentrations in cerebrospinal fluid. Optimal antibiotic dosing for the treatment and prevention of such infections should be based on robust and contextually specific pharmacokinetic data. The objects of this study were to describe and critically...

    Nilesh Kumta, Jason A. Roberts, Jeffrey Lipman, Wai Tat Wong, Gavin M. Joynt, Menino Osbert Cotta
  • Pharmacokinetic-Pharmacodynamic Target Attainment Analyses To Support Dose Selection for ME1100, an Arbekacin Inhalation Solution
    Pharmacology
    Pharmacokinetic-Pharmacodynamic Target Attainment Analyses To Support Dose Selection for ME1100, an Arbekacin Inhalation Solution

    ME1100 (arbekacin inhalation solution) is an inhaled aminoglycoside that is being developed to treat patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP and VABP, respectively). Pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses were undertaken to evaluate ME1100 regimens for the treatment of patients with HABP/VABP. The data used included a population pharmacokinetic (PPK) 4-compartment...

    Sujata M. Bhavnani, Jeffrey P. Hammel, Elizabeth A. Lakota, M. Courtney Safir, Brian D. VanScoy, Yu Nagira, Christopher M. Rubino, Nobuo Sato, Tomokazu Koresawa, Kenichiro Kondo, Paul G. Ambrose
  • Characterization of Amikacin Drug Exposure and Nephrotoxicity in an Animal Model
    Experimental Therapeutics
    Characterization of Amikacin Drug Exposure and Nephrotoxicity in an Animal Model

    Despite excellent in vitro activity, aminoglycosides are used conservatively to treat multidrug-resistant bacterial infections due to their associated nephrotoxicity. Aminoglycosides are known to accumulate in the kidneys, but the quantitative relationship between drug exposures and nephrotoxicity is not well established. To bridge the knowledge gap, the objective of this study was to develop an animal model with clinically...

    Katrina Chan, Kimberly R. Ledesma, Weiqun Wang, Vincent H. Tam
  • Unraveling the Gentamicin Drug Product Complexity Reveals Variation in Microbiological Activities and Nephrotoxicity
    Pharmacology
    Unraveling the Gentamicin Drug Product Complexity Reveals Variation in Microbiological Activities and Nephrotoxicity

    The gentamicin drug product is a complex mixture of numerous components, many of which have not individually undergone safety and efficacy assessments. This is in contrast to the majority of medicines that require rigorous characterizations of trace impurities and are dosed as single components. In gentamicin, four components, known as gentamicin congeners C1, C1a, C2, and C2a, comprise the majority of the mixture. A liquid...

    Zackery P. Bulman, Ryan Cirz, Darin Hildebrandt, Tim Kane, Zuelay Rosario, Ken Wlasichuk, Minjong Park, Logan D. Andrews
  • Novel Aminoglycoside-Tolerant Phoenix Colony Variants of <span class="named-content genus-species" id="named-content-1">Pseudomonas aeruginosa</span>
    Mechanisms of Resistance
    Novel Aminoglycoside-Tolerant Phoenix Colony Variants of Pseudomonas aeruginosa

    Pseudomonas aeruginosa is an opportunistic bacterial pathogen and is known to produce biofilms. We previously showed the emergence of colony variants in the presence of tobramycin-loaded calcium sulfate beads. In this study, we characterized the variant colonies, which survived the antibiotic treatment, and identified three distinct phenotypes—classically resistant...

    Devin Sindeldecker, Kelly Moore, Anthony Li, Daniel J. Wozniak, Matthew Anderson, Devendra H. Dusane, Paul Stoodley
  • Open Access
    Evidence for Expanding the Role of Streptomycin in the Management of Drug-Resistant <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span>
    Mechanisms of Resistance
    Evidence for Expanding the Role of Streptomycin in the Management of Drug-Resistant Mycobacterium tuberculosis

    In 2019, the WHO tuberculosis (TB) treatment guidelines were updated to recommend only limited use of streptomycin, in favor of newer agents or amikacin as the preferred aminoglycoside for drug-resistant Mycobacterium tuberculosis. However, the emergence of resistance to newer drugs, such as bedaquiline, has prompted a reanalysis of antitubercular drugs in search of...

    Keira A. Cohen, Katharine E. Stott, Vanisha Munsamy, Abigail L. Manson, Ashlee M. Earl, Alexander S. Pym
  • Activity of Plazomicin Tested against <em>Enterobacterales</em> Isolates Collected from U.S. Hospitals in 2016–2017: Effect of Different Breakpoint Criteria on Susceptibility Rates among Aminoglycosides
    Susceptibility
    Activity of Plazomicin Tested against Enterobacterales Isolates Collected from U.S. Hospitals in 2016–2017: Effect of Different Breakpoint Criteria on Susceptibility Rates among Aminoglycosides

    Plazomicin was active against 97.0% of 8,783 Enterobacterales isolates collected in the United States (2016 and 2017), and only 6 isolates carried 16S rRNA methyltransferases conferring resistance to virtually all aminoglycosides. Plazomicin (89.2% to 95.9% susceptible) displayed greater activity than amikacin (72.5% to 78.6%), gentamicin (30.4% to 45.9%), and tobramycin (7.8% to 22.4%) against carbapenem-resistant and...

    Mariana Castanheira, Helio S. Sader, Rodrigo E. Mendes, Ronald N. Jones
  • Production of Norspermidine Contributes to Aminoglycoside Resistance in <em>pmrAB</em> Mutants of <span class="named-content genus-species" id="named-content-1">Pseudomonas aeruginosa</span>
    Mechanisms of Resistance
    Production of Norspermidine Contributes to Aminoglycoside Resistance in pmrAB Mutants of Pseudomonas aeruginosa

    Emergence of resistance to polymyxins in Pseudomonas aeruginosa is mainly due to mutations in two-component systems that promote the addition of 4-amino-4-deoxy-l-arabinose to the lipopolysaccharide (LPS) through upregulation of operon arnBCADTEF-ugd (arn) expression. Here, we demonstrate that mutations occurring in different...

    Arnaud Bolard, Monika Schniederjans, Susanne Haüssler, Pauline Triponney, Benoît Valot, Patrick Plésiat, Katy Jeannot

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