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Journal ArticleDOI

Practical applications and feasibility of efflux pump inhibitors in the clinic--a vision for applied use.

Olga Lomovskaya, +1 more
- 30 Mar 2006 - 
- Vol. 71, Iss: 7, pp 910-918
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TLDR
Second-generation programs have been initiated and show early promise to significantly improve the clinical usefulness of currently available and future antibiotics against otherwise recalcitrant Gram-negative infections.
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This article is published in Biochemical Pharmacology.The article was published on 2006-03-30. It has received 393 citations till now. The article focuses on the topics: Drug resistance & Antibiotic resistance.

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Citations
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Acinetobacter baumannii: Emergence of a Successful Pathogen

TL;DR: This review details the significant advances that have been made in understanding of this remarkable organism over the last 10 years, including current taxonomy and species identification, issues with susceptibility testing, mechanisms of antibiotic resistance, global epidemiology, clinical impact of infection, host-pathogen interactions, and infection control and therapeutic considerations.
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A brief history of the antibiotic era: lessons learned and challenges for the future.

TL;DR: This article gives a very brief overview of the antibiotic era, beginning from the discovery of first antibiotics until the present day situation, which is marred by the emergence of hard-to-treat multiple antibiotic-resistant infections.
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Challenges of Antibacterial Discovery

TL;DR: The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort.
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The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

TL;DR: This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps, with particular focus on AcrAB-TolC and Mex pumps.
References
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Journal ArticleDOI

Molecular Basis of Bacterial Outer Membrane Permeability Revisited

TL;DR: This review summarizes the development in the field since the previous review and begins to understand how this bilayer of the outer membrane can retard the entry of lipophilic compounds, owing to increasing knowledge about the chemistry of lipopolysaccharide from diverse organisms and the way in which lipopoly Saccharide structure is modified by environmental conditions.
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Pharmacokinetic/Pharmacodynamic Parameters: Rationale for Antibacterial Dosing of Mice and Men

TL;DR: The potential value of using pharmacokinetic/pharmacodynamic parameters as guides for establishing optimal dosing regimens for new and old drugs and for new emerging pathogens and resistant organisms should make the continuing search for the therapeutic rationale of antibacterial dosing of mice and men worthwhile.
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Prevention of drug access to bacterial targets: permeability barriers and active efflux

TL;DR: As the pharmaceutical industry succeeds in producing agents that can overcome specific mechanisms of bacterial resistance, less specific resistance mechanisms such as permeability barriers and multidrug active efflux may become increasingly significant in the clinical setting.
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Efflux-Mediated Drug Resistance in Bacteria

TL;DR: Fluoroquinolones and β-lactams of the latest generations are likely to select for overproduction mutants of these pumps and make the bacteria resistant in one step to practically all classes of antibacterial agents.
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Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export

TL;DR: The structure of TolC is reported, revealing a distinctive and previously unknown fold that provides an explanation of how the cell cytosol is connected to the external environment during export, and suggests a general mechanism for the action of bacterial efflux pumps.
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