The Experts below are selected from a list of 19737 Experts worldwide ranked by ideXlab platform
Yohei Doi - One of the best experts on this subject based on the ideXlab platform.
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coproduction of novel 16s rrna methylase rmtd and metallo β lactamase spm 1 in a panresistant pseudomonas aeruginosa isolate from brazil
Antimicrobial Agents and Chemotherapy, 2007Co-Authors: Yohei Doi, Doroti De Oliveira Garcia, Jennifer Adams, David L PatersonAbstract:Serious infections with Pseudomonas aeruginosa are frequently treated with the combination of a beta-lactam antimicrobial and an Aminoglycoside. P. aeruginosa strain PA0905 was isolated in 2005 from an inpatient in Brazil. It showed a panresistant phenotype that included resistance to beta-lactams, Aminoglycosides, and fluoroquinolones. The beta-lactam resistance was conferred by the production of the metallo-beta-lactamase SPM-1. No inhibitory zone was observed when a disk diffusion test was performed with the semisynthetic Aminoglycoside arbekacin, raising suspicion of 16S rRNA methylase production. A cloning experiment subsequently revealed the presence of a novel 16S rRNA methylase, RmtD, which accounted for the high-level resistance to all 4,6-disubstituted deoxystreptamine Aminoglycosides, such as amikacin, tobramycin, and gentamicin. RmtD shared a moderate degree of identity with RmtA, another 16S rRNA methylase that was initially reported to occur in P. aeruginosa in Japan in 2003. This is the first identification of Aminoglycoside resistance mediated by a 16S rRNA methylase in South America. This is also the first report to document coproduction of a metallo-beta-lactamase and a 16S rRNA methylase, a combination that would severely compromise therapeutic options for the infected patients.
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plasmid mediated 16s rrna methylase in serratia marcescens conferring high level resistance to Aminoglycosides
Antimicrobial Agents and Chemotherapy, 2004Co-Authors: Yohei Doi, Keiko Yokoyama, Kunikazu Yamane, Junichi Wachino, Naohiro Shibata, Tetsuya Yagi, Keigo Shibayama, Haru Kato, Yoshichika ArakawaAbstract:Serratia marcescens S-95, which displayed an unusually high degree of resistance to Aminoglycosides, including kanamycins and gentamicins, was isolated in 2002 from a patient in Japan. The resistance was mediated by a large plasmid which was nonconjugative but transferable to an Escherichia coli recipient by transformation. The gene responsible for the Aminoglycoside resistance was cloned and sequenced. The deduced amino acid sequence of the resistance gene shared 82% identity with RmtA, which was recently identified as 16S rRNA methylase conferring high-level Aminoglycoside resistance in Pseudomonas aeruginosa. Histidine-tagged recombinant protein showed methylation activity against E. coli 16S rRNA. The novel Aminoglycoside resistance gene was therefore designated rmtB. The genetic environment of rmtB was further investigated. The sequence immediately upstream of rmtB contained the right end of transposon Tn3, including bla(TEM), while an open reading frame possibly encoding a transposase was identified downstream of the gene. This is the first report describing 16S rRNA methylase production in S. marcescens. The Aminoglycoside resistance mechanism mediated by production of 16S rRNA methylase and subsequent ribosomal protection used to be confined to Aminoglycoside-producing actinomycetes. However, it is now identified among pathogenic bacteria, including Enterobacteriaceae and P. aeruginosa in Japan. This is a cause for concern since other treatment options are often limited in patients requiring highly potent Aminoglycosides such as amikacin and tobramycin.
David L Paterson - One of the best experts on this subject based on the ideXlab platform.
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coproduction of novel 16s rrna methylase rmtd and metallo β lactamase spm 1 in a panresistant pseudomonas aeruginosa isolate from brazil
Antimicrobial Agents and Chemotherapy, 2007Co-Authors: Yohei Doi, Doroti De Oliveira Garcia, Jennifer Adams, David L PatersonAbstract:Serious infections with Pseudomonas aeruginosa are frequently treated with the combination of a beta-lactam antimicrobial and an Aminoglycoside. P. aeruginosa strain PA0905 was isolated in 2005 from an inpatient in Brazil. It showed a panresistant phenotype that included resistance to beta-lactams, Aminoglycosides, and fluoroquinolones. The beta-lactam resistance was conferred by the production of the metallo-beta-lactamase SPM-1. No inhibitory zone was observed when a disk diffusion test was performed with the semisynthetic Aminoglycoside arbekacin, raising suspicion of 16S rRNA methylase production. A cloning experiment subsequently revealed the presence of a novel 16S rRNA methylase, RmtD, which accounted for the high-level resistance to all 4,6-disubstituted deoxystreptamine Aminoglycosides, such as amikacin, tobramycin, and gentamicin. RmtD shared a moderate degree of identity with RmtA, another 16S rRNA methylase that was initially reported to occur in P. aeruginosa in Japan in 2003. This is the first identification of Aminoglycoside resistance mediated by a 16S rRNA methylase in South America. This is also the first report to document coproduction of a metallo-beta-lactamase and a 16S rRNA methylase, a combination that would severely compromise therapeutic options for the infected patients.
Matthew E Falagas - One of the best experts on this subject based on the ideXlab platform.
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do we still need the Aminoglycosides
International Journal of Antimicrobial Agents, 2009Co-Authors: Emanuele Durantemangoni, Alexandros P Grammatikos, Riccardo Utili, Matthew E FalagasAbstract:Since the introduction into clinical practice of the Aminoglycoside class of antibiotics, a number of other antimicrobial agents with improved safety profile have entered the market. Studies have failed to demonstrate the superiority of Aminoglycoside-containing regimens in a number of infection settings. This has raised doubts regarding the actual clinical utility of Aminoglycosides. However, the recent emergence of infections due to Gram-negative bacterial strains with advanced patterns of antimicrobial resistance has prompted physicians to reconsider these ‘old’ antibacterial agents. This revived interest in the use of Aminoglycosides has brought back to light the debate on the two major issues related to these compounds, namely the spectrum of antimicrobial susceptibility and toxicity. Although some of the Aminoglycosides retain activity against the majority of Gram-negative clinical bacterial isolates in many parts of the world, the relatively frequent occurrence of nephrotoxicity and ototoxicity during Aminoglycoside treatment make physicians reluctant to use these compounds in everyday practice. We believe that recent advances in the understanding of the effect of various dosage schedules of Aminoglycosides on toxicity combined with the retained (to a considerable degree) activity against the majority of Gram-negative bacterial isolates make this class of antibiotics still valuable in today’s clinical practice.
Sylvie Garneautsodikova - One of the best experts on this subject based on the ideXlab platform.
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exploring the substrate promiscuity of drug modifying enzymes for the chemoenzymatic generation of n acylated Aminoglycosides
ChemBioChem, 2009Co-Authors: Keith D Green, Wei Chen, Jacob L Houghton, Micha Fridman, Sylvie GarneautsodikovaAbstract:Aminoglycosides are broad-spectrum antibiotics commonly used for the treatment of serious bacterial infections. Decades of clinical use have led to the widespread emergence of bacte- rial resistance to this family of drugs limiting their efficacy in the clinic. Here, we report the development of a methodology that utilizes Aminoglycoside acetyltransferases (AACs) and un- natural acyl coenzyme A analogues for the chemoenzymatic generation of N-acylated Aminoglycoside analogues. Genera- tion of N-acylated Aminoglycosides is followed by a simple qualitative test to assess their potency as potential antibacteri- als. The studied AACs (AAC(6')-APH(2'') and AAC(3)-IV) show di- verse substrate promiscuity towards a variety of aminoglyco- sides as well as acyl coenzyme A derivatives. The enzymes were also used for the sequential generation of homo- and hetero-di-N-acylated Aminoglycosides. Following the clinical success of the N-acylated amikacin and arbekacin, our chemo- enzymatic approach offers access to regioselectively N-acylated Aminoglycosides in quantities that allow testing of the antibac- terial potential of the synthetic analogues making it possible to decide which molecules will be worth synthesizing on a larger scale.
H A Bruining - One of the best experts on this subject based on the ideXlab platform.
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experience with a once daily dosing program of Aminoglycosides in critically ill patients
Intensive Care Medicine, 2002Co-Authors: Steven L Buijk, Johan W Mouton, Inge C Gyssens, Henri A Verbrugh, H A BruiningAbstract:Background. As Aminoglycosides show concentration-dependent killing, once-daily Aminoglycoside (ODA) regimens have been instituted. Data on experience with ODA regimens in critically ill patients are limited.