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beta-lactams

  • First Penicillin-Binding Protein Occupancy Patterns for 15 β-Lactams and β-Lactamase Inhibitors in <span class="named-content genus-species" id="named-content-1">Mycobacterium abscessus</span>
    Pharmacology
    First Penicillin-Binding Protein Occupancy Patterns for 15 β-Lactams and β-Lactamase Inhibitors in Mycobacterium abscessus

    Mycobacterium abscessus causes serious infections that often require over 18 months of antibiotic combination therapy. There is no standard regimen for the treatment of M. abscessus infections, and the multitude of combinations that have been used clinically have had low success rates and high rates...

    Alaa R. M. Sayed, Nirav R. Shah, Kari B. Basso, Manasi Kamat, Yuanyuan Jiao, Bartolome Moya, Dhruvitkumar S. Sutaria, Yinzhi Lang, Xun Tao, Weiguo Liu, Eunjeong Shin, Jieqiang Zhou, Carolin Werkman, Arnold Louie, George L. Drusano, Jürgen B. Bulitta
  • 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
  • Intrapulmonary Pharmacokinetics of Cefepime and Enmetazobactam in Healthy Volunteers: Towards New Treatments for Nosocomial Pneumonia
    Pharmacology
    Intrapulmonary Pharmacokinetics of Cefepime and Enmetazobactam in Healthy Volunteers: Towards New Treatments for Nosocomial Pneumonia

    Cefepime-enmetazobactam is a novel β-lactam–β-lactamase inhibitor combination with broad-spectrum antimicrobial activity against a range of multidrug-resistant Enterobacteriaceae. This agent is being developed for a range of serious hospital infections. An understanding of the extent of partitioning of β-lactam–β-lactamase inhibitor combinations into the human lung is required to better understand the potential role of cefepime...

    Shampa Das, Richard Fitzgerald, Asad Ullah, Marcin Bula, Andrea M. Collins, Elena Mitsi, Jesus Reine, Helen Hill, Jamie Rylance, Daniela M. Ferreira, Karen Tripp, Andrea Bertasini, Samantha Franzoni, Mameli Massimiliano, Omar Lahlou, Paola Motta, Philip Barth, Patrick Velicitat, Philipp Knechtle, William Hope
  • Matched Case-Control Study of the Long-Term Impact of Beta-Lactam Antibiotic Allergy Testing
    Clinical Therapeutics
    Matched Case-Control Study of the Long-Term Impact of Beta-Lactam Antibiotic Allergy Testing

    Whereas the short-term impacts of antibiotic allergy testing on delabeling and antibiotic usage have been demonstrated, the long-term impacts have been less well defined. In a single-center matched case-control study from Melbourne, Australia, we demonstrate that a beta-lactam antibiotic allergy testing program has a significant impact on antibiotic usage and infection-related outcomes. This study supports implementation of an...

    Jason A. Trubiano, Nada Marhoon, Sara Vogrin, Kyra Y. L. Chua, Natasha E. Holmes
  • <em>In Vivo</em> Activity of QPX7728, an Ultrabroad-Spectrum Beta-Lactamase Inhibitor, in Combination with Beta-Lactams against Carbapenem-Resistant <span class="named-content genus-species" id="named-content-1">Klebsiella pneumoniae</span>
    Pharmacology
    In Vivo Activity of QPX7728, an Ultrabroad-Spectrum Beta-Lactamase Inhibitor, in Combination with Beta-Lactams against Carbapenem-Resistant Klebsiella pneumoniae

    Resistance to beta-lactams has created a major clinical issue. QPX7728 is a novel ultrabroad-spectrum cyclic boronic acid beta-lactamase inhibitor with activity against both serine and metallo-beta-lactamases developed to address this resistance for use in combination with beta-lactam antibiotics. The objective of these studies was to evaluate the activity of QPX7728 in combination with multiple beta-lactams against carbapenem-resistant...

    Mojgan Sabet, Ziad Tarazi, David C. Griffith
  • 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 Basis and Binding Kinetics of Vaborbactam in Class A β-Lactamase Inhibition
    Clinical Therapeutics
    Structural Basis and Binding Kinetics of Vaborbactam in Class A β-Lactamase Inhibition

    Class A β-lactamases are a major cause of β-lactam resistance in Gram-negative bacteria. The recently FDA-approved cyclic boronate vaborbactam is a reversible covalent inhibitor of class A β-lactamases, including CTX-M extended-spectrum β-lactamase and KPC carbapenemase, both frequently observed in the clinic. Intriguingly, vaborbactam displayed different binding kinetics and cell-based activity for these two enzymes, despite their...

    Orville A. Pemberton, Ruslan Tsivkovski, Maxim Totrov, Olga Lomovskaya, Yu Chen
  • The Emerging Role of β-Lactams in the Treatment of Methicillin-Resistant <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span> Bloodstream Infections
    Editor's Pick Minireview
    The Emerging Role of β-Lactams in the Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections

    Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with substantial morbidity and mortality. Monotherapy with first-line antimicrobials such as vancomycin (VAN; glycopeptide) and daptomycin (DAP; lipopeptide) are inadequate in some cases due to reduced antibiotic susceptibilities or therapeutic failure. In recent years, β-...

    Kyle C. Molina, Taylor Morrisette, Matthew A. Miller, Vanthida Huang, Douglas N. Fish
  • Open Access
    Scope and Predictive Genetic/Phenotypic Signatures of Bicarbonate (NaHCO<sub>3</sub>) Responsiveness and β-Lactam Sensitization in Methicillin-Resistant <span class="named-content genus-species" id="named-content-1">Staphylococcus aureus</span>
    Susceptibility
    Scope and Predictive Genetic/Phenotypic Signatures of Bicarbonate (NaHCO3) Responsiveness and β-Lactam Sensitization in Methicillin-Resistant Staphylococcus aureus

    Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to β-lactams. We investigated the prevalence of this phenotype (NaHCO3 responsiveness) to two β-lactams among 58 clinical MRSA bloodstream isolates. Of...

    Selvi C. Ersoy, Mariam Otmishi, Vanessa T. Milan, Liang Li, Youngju Pak, Jose Mediavilla, Liang Chen, Barry Kreiswirth, Henry F. Chambers, Richard A. Proctor, Yan Q. Xiong, Vance G. Fowler, Arnold S. Bayer
  • Dose Optimization of Cefpirome Based on Population Pharmacokinetics and Target Attainment during Extracorporeal Membrane Oxygenation
    Clinical Therapeutics
    Dose Optimization of Cefpirome Based on Population Pharmacokinetics and Target Attainment during Extracorporeal Membrane Oxygenation

    To obtain the optimal dosage regimen in patients receiving extracorporeal membrane oxygenation (ECMO), we developed a population pharmacokinetics model for cefpirome and performed pharmacodynamic analyses. This prospective study included 15 patients treated with cefpirome during ECMO. Blood samples were collected during ECMO (ECMO-ON) and after ECMO (ECMO-OFF) at predose and 0.5 to 1, 2 to 3, 4 to 6, 8 to 10, and 12 h after cefpirome...

    Soyoung Kang, June Young Jang, Jongsung Hahn, Dasohm Kim, Jun Yeong Lee, Kyoung Lok Min, Seungwon Yang, Jin Wi, Min Jung Chang

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