Approaches to Reduce Antibiotic Resistance in the Community

Department of Microbiology, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
The Pediatric Infectious Disease Journal (Impact Factor: 2.72). 11/2006; 25(10):977-80. DOI: 10.1097/01.inf.0000239271.10784.1e
Source: PubMed


During the last two decades, there has been an alarming worldwide increase of resistance to antibiotics of bacterial pathogens responsible for community-acquired infections. This dramatic evolution is generally attributed to the extensive use of antibiotics and the selective pressure on the bacterial strains. To decrease antibiotics resistance in the community, several approaches should be considered through: reducing unnecessary antibiotic prescriptions: inappropriate antibiotic treatments are becoming a major issue; however, few studies have shown a decrease of antibiotic resistance following a reduction of antibiotic use in the community;decreasing the prescriptions of the more selective antibiotic compounds for some bacterial species, eg macrolides and group A streptococcus (GAS), trimethoprim-sulfamethoxazole and pneumococcus; using an optimal dosage and duration of antibiotic regimens chosen; some studies have suggested that low dosage and long treatment duration could promote antibiotic resistance; and implementing the pneumococcal conjugate vaccines; several studies have shown a decline in the proportion of penicillin nonsusceptible Streptococcus pneumoniae isolated from invasive pneumococcal diseases or nasopharyngeal flora. The combination of these approaches, particularly the reduction of antibiotic use and pneumococcal immunization, could be synergistic.

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    • "Reducing the mortality rate from bacterial infections and diseases, antibiotics have become cornerstones of modern medicine required by many common procedures such as transplantation, chemotherapy for cancer or surgery [1]. However, antibiotics lose their efficiency after a period of months to years [2] [3] [4], eventually producing new strains of bacteria resistant to the given drug. Since old antibiotics lose their efficiency faster than new ones can be developed [5], there is currently no antibiotic in clinical use, to which resistance has not yet been reported [6] [7]. "
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    ABSTRACT: Representing a physiological "Achilles' heel", the cell wall precursor lipid II (LII) is a prime target for various classes of antibiotics. Over the years LII-binding agents have been recognized as promising candidates and templates in the search for new antibacterial compounds to complement or replace existing drugs. To elucidate the molecular structural basis underlying LII functional mechanism and to better understand if and how lantibiotic binding alters the molecular behavior of LII, we performed molecular dynamics (MD) simulations of phospholipid membrane-embedded LII in absence and presence of the LII-binding lantibiotic nisin. In a series of 2 x 4 independent, unbiased 100ns MD simulations we sampled the conformational dynamics of nine LII as well as nine LII-nisin complexes embedded in an aqueous 150mM NaCl / POPC phospholipid membrane environment. We found that nisin binding to LII induces a reduction of LII mobility and flexibility, an outward shift of the LII pentapeptide, an inward movement of the LII disaccharide section, and an overall deeper insertion of the LII tail group into the membrane. The latter process might indicate an initial step in adopting a stabililzing, scaffold-like structure in the process of nisin-induced membrane leakage. At the same time nisin conformation and LII interaction remain similar to the 1WCO LII-nisin NMR solution structure.
    Biochimica et Biophysica Acta (BBA) - Biomembranes 08/2014; 1838(12). DOI:10.1016/j.bbamem.2014.07.024 · 3.84 Impact Factor
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    • "The discovery, development and clinical exploitation of antibiotics count among the most significant medical advances in history. However, antibiotics lose their efficiency after a period of months to years [35–37], eventually producing new strains of resistant bacteria, as the continuous application of antibiotics wipes out the cells in a bacteria population sensitive to the drug given. At the same time this effect creates perfect survival conditions for the fraction of bacteria immune to the pharmaceuticals applied. "
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    ABSTRACT: Over-expression of multidrug efflux pumps of the Resistance Nodulation Division (RND) protein super family counts among the main causes for microbial resistance against pharmaceuticals. Understanding the molecular basis of this process is one of the major challenges of modern biomedical research, involving a broad range of experimental and computational techniques. Here we review the current state of RND transporter investigation employing molecular dynamics simulations providing conformational samples of transporter components to obtain insights into the functional mechanism underlying efflux pump-mediated antibiotics resistance in Escherichia coli and Pseudomonas aeruginosa.
    Computational and Structural Biotechnology Journal 02/2013; 5(6):e201302008. DOI:10.5936/csbj.201302008
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    ABSTRACT: Naturally occurring and synthetic peptides may be a novel class of clinically useful antibiotics. A large body of experimental data on structure function relationships for such peptides is available, but the molecular mechanism of their action remains elusive in most cases. Computer simulations can give detailed insights into the interactions between peptides and lipid bilayers, at least one crucial step in the antimicrobial mechanism. Here we review recent simulations of antimicrobial peptides and discuss potential future contributions of computer simulations in understanding and ultimately designing antimicrobial peptides.
    Current Medicinal Chemistry 02/2007; 14(26):2789-98. DOI:10.2174/092986707782360105 · 3.85 Impact Factor
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