ketolides

Summary

Summary: Compounds based on ERYTHROMYCIN with the 3-cladinose replaced by a ketone. They bind the 23S part of 70S bacterial RIBOSOMES.

Top Publications

  1. pmc Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action
    Jack A Dunkle
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 107:17152-7. 2010
  2. ncbi Macrolides and ketolides: azithromycin, clarithromycin, telithromycin
    Jerry M Zuckerman
    Jefferson Medical College, Philadelphia, PA, USA
    Infect Dis Clin North Am 18:621-49, xi-. 2004
  3. ncbi Ketek--the FDA perspective
    Janice Soreth
    N Engl J Med 356:1675-6. 2007
  4. pmc Multicenter study of the mechanisms of resistance and clonal relationships of Streptococcus agalactiae isolates resistant to macrolides, lincosamides, and ketolides in Spain
    J J Gonzalez
    Servicio de Microbiologia, Hospital Vall d Hebron, Pg Vall d Hebron 119 129, 08035 Barcelona, Spain
    Antimicrob Agents Chemother 49:2525-7. 2005
  5. ncbi Hospitalization rates among patients with community-acquired pneumonia treated with telithromycin vs clarithromycin: results from two randomized, double-blind, clinical trials
    Michael S Niederman
    Department of Medicine, Winthrop University Hospital, Minneola, NY 11501, USA
    Curr Med Res Opin 20:969-80. 2004
  6. ncbi Structure-activity relationships for six ketolide antibiotics
    W S Champney
    Department of Biochemistry and Molecular Biology, J H Quillen College of Medicine, East Tennessee State University, Johnson City 37614, USA
    Curr Microbiol 42:203-10. 2001
  7. ncbi Ketolides-telithromycin, an example of a new class of antibacterial agents
    A Bryskier
    Aventis Pharma, Infectious Disease Group Clinical Pharmacology, Romainville, France
    Clin Microbiol Infect 6:661-9. 2000
  8. ncbi The FDA and the case of Ketek
    David B Ross
    George Washington University School of Medicine and Health Sciences, Washington, DC, USA
    N Engl J Med 356:1601-4. 2007
  9. ncbi Telithromycin
    J A Balfour
    Adis International Limited, Mairangi Bay, Auckland, New Zealand
    Drugs 61:815-29; discussion 830-1. 2001
  10. pmc Activity of the ketolide telithromycin is refractory to Erm monomethylation of bacterial rRNA
    Mingfu Liu
    Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK 5230 Odense M, Denmark
    Antimicrob Agents Chemother 46:1629-33. 2002

Detail Information

Publications208 found, 100 shown here

  1. pmc Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action
    Jack A Dunkle
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 107:17152-7. 2010
    ..The present data further argue that the identity of nucleotides 752, 2609, and 2055 of 23S ribosomal RNA explain in part the spectrum and selectivity of antibiotic action...
  2. ncbi Macrolides and ketolides: azithromycin, clarithromycin, telithromycin
    Jerry M Zuckerman
    Jefferson Medical College, Philadelphia, PA, USA
    Infect Dis Clin North Am 18:621-49, xi-. 2004
    ..This article reviews the pharmacokinetics, antimicrobial activity, clinical use, and adverse effects of these antimicrobial agents...
  3. ncbi Ketek--the FDA perspective
    Janice Soreth
    N Engl J Med 356:1675-6. 2007
  4. pmc Multicenter study of the mechanisms of resistance and clonal relationships of Streptococcus agalactiae isolates resistant to macrolides, lincosamides, and ketolides in Spain
    J J Gonzalez
    Servicio de Microbiologia, Hospital Vall d Hebron, Pg Vall d Hebron 119 129, 08035 Barcelona, Spain
    Antimicrob Agents Chemother 49:2525-7. 2005
    ..The erm(B), erm(TR), and mef(A) genes were present in 62%, 30.4%, and 3.8% of the isolates, respectively. There was considerable clonal diversity among them...
  5. ncbi Hospitalization rates among patients with community-acquired pneumonia treated with telithromycin vs clarithromycin: results from two randomized, double-blind, clinical trials
    Michael S Niederman
    Department of Medicine, Winthrop University Hospital, Minneola, NY 11501, USA
    Curr Med Res Opin 20:969-80. 2004
    ..To compare hospitalization rates among patients with community-acquired pneumonia (CAP) treated with oral telithromycin and clarithromycin, based on pooled data from two randomized, double-blind, multinational clinical trials...
  6. ncbi Structure-activity relationships for six ketolide antibiotics
    W S Champney
    Department of Biochemistry and Molecular Biology, J H Quillen College of Medicine, East Tennessee State University, Johnson City 37614, USA
    Curr Microbiol 42:203-10. 2001
    Six structurally related 3-keto-substituted macrolide antibiotics (ketolides) were compared for concentration-dependent inhibitory effects on growth rate, viable cell number, and protein synthesis rates in Staphylococcus aureus cells...
  7. ncbi Ketolides-telithromycin, an example of a new class of antibacterial agents
    A Bryskier
    Aventis Pharma, Infectious Disease Group Clinical Pharmacology, Romainville, France
    Clin Microbiol Infect 6:661-9. 2000
    b>Ketolides are new medicinal chemical entities. They are obtained by removing the 3-L-cladinose sugar moiety from erythronolide A and oxidation of the resulting 3-hydroxyl...
  8. ncbi The FDA and the case of Ketek
    David B Ross
    George Washington University School of Medicine and Health Sciences, Washington, DC, USA
    N Engl J Med 356:1601-4. 2007
  9. ncbi Telithromycin
    J A Balfour
    Adis International Limited, Mairangi Bay, Auckland, New Zealand
    Drugs 61:815-29; discussion 830-1. 2001
    ..first member of a new family of the macrolide-lincosamide-streptogramin-B (MLS(B)) class of antimicrobials, the ketolides. It has a good spectrum of activity against respiratory pathogens, including penicillin- and erythromycin-..
  10. pmc Activity of the ketolide telithromycin is refractory to Erm monomethylation of bacterial rRNA
    Mingfu Liu
    Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK 5230 Odense M, Denmark
    Antimicrob Agents Chemother 46:1629-33. 2002
    ..In contrast to the macrolides, monomethylation only mildly affects the antimicrobial activities of the ketolides HMR 3647 (telithromycin) and HMR 3004, and these drugs remain 16 to 250 times as potent as clarithromycin and ..
  11. ncbi Increased susceptibility of Pseudomonas aeruginosa to macrolides and ketolides in eukaryotic cell culture media and biological fluids due to decreased expression of oprM and increased outer-membrane permeability
    Julien M Buyck
    Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute, Universite Catholique de Louvain, Bruxelles, Belgium
    Clin Infect Dis 55:534-42. 2012
    ..Nevertheless, azithromycin is successfully used in cystic fibrosis patients, supposedly because of "nonantibiotic effects."..
  12. ncbi Ketolide resistance in Streptococcus pyogenes correlates with the degree of rRNA dimethylation by Erm
    Stephen Douthwaite
    Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK 5230 Odense M, Denmark
    Mol Microbiol 58:613-22. 2005
    ..pyogenes with constitutive erm(A) subtype (TR) are resistant to macrolides, but remain susceptible to ketolides such as telithromycin. Paradoxically, some strains of S...
  13. ncbi Clinical pharmacokinetics of telithromycin, the first ketolide antibacterial
    Jun Shi
    Sanofi Aventis Pharmaceuticals, Bridgewater, New Jersey, USA
    Clin Pharmacokinet 44:915-34. 2005
    ..In conclusion, telithromycin has a well characterised and reproducible pharmacokinetic profile, with pharmacokinetic/pharmacodynamic relationships supporting an oral dosage regimen of 800 mg once daily...
  14. pmc Bronchopulmonary disposition of the ketolide telithromycin (HMR 3647)
    C Muller-Serieys
    Unite de Microbiologie, Hopital Bichat Claude Bernard, 75877 Paris, France
    Antimicrob Agents Chemother 45:3104-8. 2001
    Telithromycin (HMR 3647) is the first member of a new family of antimicrobials, the ketolides, developed specifically for the treatment of community-acquired respiratory tract infections...
  15. ncbi Predicting antibacterial response from pharmacodynamic and pharmacokinetic profiles
    D P Nicolau
    Hartford Hospital, Connecticut 06102 5037, USA
    Infection 29:11-5. 2001
    ..Azithromycin, ketolides, such as telithromycin (HMR 3647), streptogramins and fluoroquinolones exhibit concentration-dependent killing ..
  16. pmc Telithromycin resistance in Streptococcus pneumoniae is conferred by a deletion in the leader sequence of erm(B) that increases rRNA methylation
    Nicole Wolter
    Respiratory and Meningeal Pathogens Research Unit, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, South Africa
    Antimicrob Agents Chemother 52:435-40. 2008
    ..Elevated erm(B) expression results in a higher level of rRNA methylation that presumably hinders telithromycin binding to the ribosome...
  17. pmc Antibiotic innovation may contribute to slowing the dissemination of multiresistant Streptococcus pneumoniae: the example of ketolides
    Lulla Opatowski
    Unité de Pharmacoépidémiologie et Maladies Infectieuses, Institut Pasteur, Paris, France
    PLoS ONE 3:e2089. 2008
    Despite increasingly frequent bacterial resistance to antibiotics, antibacterial innovation is rare. Ketolides constitute one of the very few new antibiotic classes active against Streptococcus pneumoniae developed during the last 25 ..
  18. ncbi Macrolides, ketolides, and glycylcyclines: azithromycin, clarithromycin, telithromycin, tigecycline
    Jerry M Zuckerman
    Jefferson Medical College, 1025 Walnut Street, Philadelphia, PA 19107, USA
    Infect Dis Clin North Am 23:997-1026, ix-x. 2009
    ..Telithromycin is approved for the treatment of community-acquired pneumonia. Severe hepatotoxicity has been reported with the use of telithromycin...
  19. ncbi Pharmacokinetics and comparative effects of telithromycin (HMR 3647) and clarithromycin on the oropharyngeal and intestinal microflora
    C Edlund
    Huddinge University Hospital, Karolinska Institute, Södertörns högskola, University College, Stockholm, Sweden
    J Antimicrob Chemother 46:741-9. 2000
    ..Telithromycin seems to have a more favourable ecological profile compared with clarithromycin in terms of resistance development in the normal microflora...
  20. pmc Investigating the entire course of telithromycin binding to Escherichia coli ribosomes
    Ourania N Kostopoulou
    Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece
    Nucleic Acids Res 40:5078-87. 2012
    ..Our data correlate well with recent crystallographic data and rationalize the changes in the accessibility of ribosomes to telithromycin in response to ribosomal mutations and ionic changes...
  21. ncbi The macrolide-ketolide antibiotic binding site is formed by structures in domains II and V of 23S ribosomal RNA
    L H Hansen
    Department of Molecular Biology, Odense University, Denmark
    Mol Microbiol 31:623-31. 1999
    ..These findings indicate how drug derivatization can improve the inhibition of bacteria that have macrolide resistance conferred by changes in the peptidyl transferase loop...
  22. ncbi Design, synthesis and antibacterial activity of novel ketolides bearing an aryltetrazolyl-substituted alkyl side chain
    Qiu Ling Song
    Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Huangpu Avenue 601, Guangzhou, China
    J Antibiot (Tokyo) 64:571-81. 2011
    A set of 17 novel ketolides bearing an aryltetrazolyl-substituted alkyl side chain were synthesized and evaluated for their antibacterial activities, which the aryltetrazolyl group was selected to replace the hetero-aryl moiety of the ..
  23. pmc Revisiting the structures of several antibiotics bound to the bacterial ribosome
    David Bulkley
    Departments of Chemistry, Yale University, Howard Hughes Medical Institute, New Haven, CT 06511, USA
    Proc Natl Acad Sci U S A 107:17158-63. 2010
    ....
  24. ncbi Ketolides--the modern relatives of macrolides : the pharmacokinetic perspective
    Markus Zeitlinger
    Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
    Clin Pharmacokinet 48:23-38. 2009
    ..b>Ketolides are structurally related to macrolides and were developed to overcome macrolide resistance, while sharing ..
  25. ncbi Ketolides: the future of the macrolides?
    Angela M Nilius
    Infectious Diseases Research R47T, AP52 Abbott Laboratories, Abbott Park, Illinois 60064 3537, USA
    Curr Opin Pharmacol 2:493-500. 2002
    ..b>Ketolides, semi-synthetic derivatives of erythromycin, overcome the macrolide resistance mechanisms found in Streptococcus ..
  26. ncbi Benefit-risk assessment of telithromycin in the treatment of community-acquired pneumonia
    Steven D Brown
    Clinical Microbiology Institute, Wilsonville, Oregon 97070, USA
    Drug Saf 31:561-75. 2008
    ..Although serious and sometimes fatal events have occurred in patients receiving telithromycin therapy, current data indicate that telithromycin offers an acceptable benefit risk ratio in the treatment of mild to moderate CAP...
  27. ncbi Structure-activity relationships of ketolides vs. macrolides
    S Douthwaite
    Department of Biochemistry and Molecular Biology, Odense University, Denmark
    Clin Microbiol Infect 7:11-7. 2001
    ..The ketolides, of which telithromycin is the first to reach clinical development, represent a new generation of antimicrobials ..
  28. ncbi Macrolide-ketolide inhibition of MLS-resistant ribosomes is improved by alternative drug interaction with domain II of 23S rRNA
    S Douthwaite
    Department of Molecular Biology, Odense University, DK 5230 Odense M, Denmark
    Mol Microbiol 36:183-93. 2000
    ....
  29. ncbi Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance
    Daqi Tu
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
    Cell 121:257-70. 2005
    ..coli) that stacks between them. The structure of large subunit containing a three residue deletion mutant of L22 shows a change in the L22 structure and exit tunnel shape that illuminates its macrolide resistance phenotype...
  30. ncbi Telithromycin-associated hepatotoxicity: Clinical spectrum and causality assessment of 42 cases
    Allen D Brinker
    Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA
    Hepatology 49:250-7. 2009
    ..Concurrence in assignment of causality increased after agreement on definitions of categories and interactive discussions...
  31. ncbi Telithromycin use and spontaneous reports of hepatotoxicity
    David D Dore
    Department of Community Health, Brown Medical School, Providence, RI 02903, USA
    Drug Saf 30:697-703. 2007
    ..Recent reports have described cases of telithromycin-related hepatotoxicity. The objective of this study is to quantify the effect of telithromycin use on the risk of hepatotoxicity...
  32. ncbi Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and compatative in vitro activity of the ketolide, telithromycin
    David Felmingham
    GR Micro Ltd, 7 9 William Road, London NW1 3ER, UK
    J Antimicrob Chemother 50:25-37. 2002
    ..pneumoniae and demonstrate the potential of telithromycin as a therapeutic option for the treatment of community-acquired respiratory tract infections caused by this organism...
  33. pmc Pharmacodynamics of telithromycin In vitro against respiratory tract pathogens
    I Odenholt
    Antibiotic Research Unit, Department of Infectious Diseases and Clinical Microbiology, University Hospital, Uppsala, Sweden
    Antimicrob Agents Chemother 45:23-9. 2001
    ..Overall, telithromycin exhibited long postantibiotic effects and postantibiotic sub-MIC effects for all strains investigated...
  34. ncbi Drugs of the 21st century: telithromycin (HMR 3647)--the first ketolide
    Grit Ackermann
    Institute for Medical Microbiology and Epidemiology of Infectious Diseases, University of Leipzig, Liebigstrasse 24, 04103 Leipzig, Germany
    J Antimicrob Chemother 51:497-511. 2003
    Telithromycin (HMR 3647) is the first ketolide introduced into clinical practice. Ketolides are semisynthetic derivates of erythromycin A that carry novel biological properties on the erythronolide A ring...
  35. ncbi Species-specific antibiotic-ribosome interactions: implications for drug development
    Daniel N Wilson
    Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D 14195 Berlin, Germany
    Biol Chem 386:1239-52. 2005
    ..structural data for the bacterial D50S-antibiotic complexes reveals that the mode of binding of the macrolides, ketolides, streptogramins and lincosamides is generally similar to that observed in the archaeal H50S structures...
  36. pmc 23S rRNA base pair 2057-2611 determines ketolide susceptibility and fitness cost of the macrolide resistance mutation 2058A-->G
    Peter Pfister
    Institut fur Medizinische Mikrobiologie, Universitat Zurich, Gloriastrasse 30 32, CH 8006 Zurich, Switzerland
    Proc Natl Acad Sci U S A 102:5180-5. 2005
    ..However, this mutation is associated with a disparate resistance phenotype: It confers high-level resistance to ketolides in mycobacteria but only marginally affects ketolide susceptibility in streptococci...
  37. ncbi Structural basis for the antibiotic activity of ketolides and azalides
    Frank Schlünzen
    Max Planck Research Unit for Ribosomal Structure, 22603, Hamburg, Germany
    Structure 11:329-38. 2003
    ..The additional molecule also interacts with two proteins, L4 and L22, implicated in macrolide resistance. These studies illuminated and rationalized the enhanced activity of the drugs against specific macrolide-resistant bacteria...
  38. ncbi Clinical and bacteriological efficacy and safety of 5 and 7 day regimens of telithromycin once daily compared with a 10 day regimen of clarithromycin twice daily in patients with mild to moderate community-acquired pneumonia
    Guy Tellier
    Zoom International Clinical Research Group, 290 Montigny Street, Saint Jerome, Quebec J7Z 5T3, Canada
    J Antimicrob Chemother 54:515-23. 2004
    ..Bacteriological efficacy was also compared...
  39. pmc Structural insight into the antibiotic action of telithromycin against resistant mutants
    Rita Berisio
    Max Planck Research Unit for Ribosomal Structure, Hamburg, Germany
    J Bacteriol 185:4276-9. 2003
    ..Comparisons to other clinically relevant macrolides provided structural insights into its enhanced activity against macrolide-resistant strains...
  40. pmc Comparison of in vitro activities of ketolides, macrolides, and an azalide against the spirochete Borrelia burgdorferi
    Klaus Peter Hunfeld
    Institute of Medical Microbiology, University Hospital of Frankfurt, D 60596 Frankfurt Main, Germany
    Antimicrob Agents Chemother 48:344-7. 2004
    Two ketolides, three macrolides, and one azalide were tested in vitro against 17 isolates of the B. burgdorferi s.l. complex...
  41. ncbi Comparative activity of quinolones, macrolides and ketolides against Legionella species using in vitro broth dilution and intracellular susceptibility testing
    Janet E Stout
    VA Pittsburgh Healthcare System, VA Medical Center, Infectious Disease Section, University Drive C, Pittsburgh, PA 15240, USA
    Int J Antimicrob Agents 25:302-7. 2005
    ..of quinolones (trovafloxacin, gemifloxacin, levofloxacin, ciprofloxacin, moxifloxacin and grepafloxacin), ketolides (ABT-773 and telithromycin) and macrolides (clarithromycin, azithromycin and erythromycin) were evaluated ..
  42. ncbi Activity of cefditoren against clinical isolates of Streptococcus pneumoniae showing non-susceptibility to penicillins, cephalosporins, macrolides, ketolides or quinolones
    Asuncion Fenoll
    Int J Antimicrob Agents 29:224-6. 2007
  43. ncbi Trends in anti-bacterial resistance among Streptococcus pneumoniae isolated in the USA, 2000-2003: PROTEKT US years 1-3
    Stephen G Jenkins
    Clinical Microbiology Laboratories, Department of Pathology, Mount Sinai School of Medicine, Mount Sinai Medical Center, New York, NY 10029 6574, USA
    J Infect 51:355-63. 2005
    ..To determine geographic and temporal trends in anti-bacterial resistance among Streptococcus pneumoniae isolated from patients with respiratory tract infections as part of the PROTEKT US surveillance study (2000-2003)...
  44. ncbi Comparative in vitro activity of telithromycin against macrolide-resistant and -susceptible Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae
    Fiona Walsh
    Department of Medical Microbiology, Medical School, University of Edinburgh, Edinburgh EH8 9AG, UK
    J Antimicrob Chemother 53:793-6. 2004
    ..The second objective was to identify the influence of the erm(B) and mef(A) genes on the susceptibility of Streptococcus pneumoniae to telithromycin...
  45. ncbi [in vitro activity of telithromycin against Haemophilus influenzae]
    H Dabernat
    Laboratoire de Microbiologie, Hopital Purpan, 31059 Toulouse, France
    Pathol Biol (Paris) 50:58-62. 2002
    ..Distribution of diameter zones showed a similar pattern to that of MICs but correlation between MICs and diameter zones was poor with correlation coefficients inferior to 0.5 whatever the agar media used...
  46. pmc Activities of telithromycin against 13,874 Streptococcus pneumoniae isolates collected between 1999 and 2003
    David J Farrell
    GR Micro Limited, London, United Kingdom
    Antimicrob Agents Chemother 48:1882-4. 2004
    ..The telithromycin MICs for 10 isolates (0.07%) were >/=4 micro g/ml, and these 10 isolates contained erm(B); there was no evidence of reproducible clonal spread between centers...
  47. ncbi Impact of ketolides on resistance selection and ecologic effects during treatment for respiratory tract infections
    C E Nord
    Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden
    Microb Drug Resist 10:255-63. 2004
    b>Ketolides are a new class of antibacterials that have been specifically developed for the treatment of community-acquired respiratory tract infections in an era of increasing resistance among major etiologic pathogens...
  48. ncbi Will resistance to ketolides develop in Streptococcus pneumoniae?
    R Leclercq
    CHU de Caen, Service de Microbiologie, France
    J Infect 44:11-6. 2002
    ..The ketolides, of which telithromycin is the first to be registered for clinical use, represent a new class of antibacterials ..
  49. ncbi Pneumococcal resistance to macrolides, lincosamides, ketolides, and streptogramin B agents: molecular mechanisms and resistance phenotypes
    Paul H Edelstein
    Dept of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, 19104 4283, USA
    Clin Infect Dis 38:S322-7. 2004
    The macrolides, lincosamides, ketolides, and streptogramin B agents (the MLKS(B) antimicrobial agents) have related chemical structures and share similar molecular targets on the 50S ribosomal subunit of Streptococcus pneumoniae...
  50. pmc Effect of efflux on telithromycin and macrolide susceptibility in Haemophilus influenzae
    Tatiana Bogdanovich
    Department of Pathology, Hershey Medical Center, P O Box 850, Hershey, Pennsylvania 17033, USA
    Antimicrob Agents Chemother 50:893-8. 2006
    ..in 58 clinical strains of Haemophilus influenzae with various susceptibilities to macrolides, azalides, and ketolides. Efflux pumps were studied by measuring accumulation of radioactive [3H]telithromycin and [N-methyl-3H]..
  51. pmc Antibiotic activity of telithromycin and comparators against bacterial pathogens isolated from 3,043 patients with acute exacerbation of chronic bronchitis
    Sanjay Sethi
    University at Buffalo SUNY, USA
    Ann Clin Microbiol Antimicrob 4:5. 2005
    ..Antibacterial resistance is increasing worldwide and little surveillance data exist concerning pathogens isolated from patients with AECB...
  52. ncbi Streptococcus pneumoniae and Streptococcus pyogenes isolated from a paediatric population in Great Britain and Ireland: the in vitro activity of telithromcycin versus comparators
    J Shackcloth
    GR Micro Limited, 7 9 William Road, London NW1 3ER, UK
    J Infect 48:229-35. 2004
    ..To determine the distribution of macrolide resistance genes within the erythromycin resistant population...
  53. ncbi Activity of five quinolones, three macrolides and telithromycin against 12 Haemophilus influenzae strains with different resistance phenotypes
    G A Pankuch
    Department of Pathology, Hershey Medical Center, Hershey, PA 17033, USA
    Clin Microbiol Infect 11:1040-4. 2005
    ..0-8.0 mg/L), except for two strains without efflux systems (0.0125-0.5 mg/L) and two with efflux systems and ribosomal protein mutations (> 64.0 mg/L), and were bactericidal against eight to ten strains tested at 2 x MIC after 24 h...
  54. ncbi Tissue kinetics of telithromycin, the first ketolide antibacterial
    C Muller-Serieys
    Hopital Bichat Claude Bernard, 75877 Paris Cedex 18, France
    J Antimicrob Chemother 53:149-57. 2004
    ..The tissue kinetics profile of telithromycin, together with its microbiological profile, makes it a promising new antibacterial for the treatment of community-acquired RTIs...
  55. ncbi Telithromycin: a ketolide antibiotic for treatment of respiratory tract infections
    John R Lonks
    Division of Infectious Diseases, Brown Medical School and Miriam Hospital, Providence, RI 02912, USA
    Clin Infect Dis 40:1657-64. 2005
    ..Unique visual adverse effects occurred in 0.27%-2.1% of patients receiving telithromycin therapy. Its enhanced activity against some common respiratory pathogens makes it a valuable addition to the available macrolides...
  56. ncbi Demographic analysis of antimicrobial resistance among Streptococcus pneumoniae: worldwide results from PROTEKT 1999-2000
    Daryl Hoban
    Health Sciences Centre, Department of Clinical Microbiology, Winnipeg, Man, Canada
    Int J Infect Dis 9:262-73. 2005
    ..The influence of demographic factors upon antimicrobial resistance among 3362 isolates of Streptococcus pneumoniae from 25 countries was investigated, using univariate comparison and multivariate logistic regression...
  57. ncbi Impact of carbon dioxide on the susceptibility of key respiratory tract pathogens to telithromycin and azithromycin
    Sam K Bouchillon
    Laboratories International for Microbiology Studies, Inc, Schaumburg, IL 60173 3817, USA
    J Antimicrob Chemother 56:224-7. 2005
    ....
  58. pmc In vitro activity of telithromycin (HMR3647), a new ketolide, against clinical isolates of Mycoplasma pneumoniae in Japan
    T Yamaguchi
    Department of Laboratory Medicine, Nagasaki University School of Medicine, Nagasaki 852 8501, Japan
    Antimicrob Agents Chemother 44:1381-2. 2000
    ..00097 microg/ml, justifying clinical studies to determine its efficacy for treatment of M. pneumoniae...
  59. pmc In vivo efficacy of telithromycin (HMR3647) against Streptococcus pneumoniae and Haemophilus influenzae
    H Okamoto
    Department of Microbiology, Toho University School of Medicine, Omori Nishi, Ota ku, Tokyo, Japan
    Antimicrob Agents Chemother 45:3250-2. 2001
    ..In respiratory tract infections caused by erythromycin A-susceptible S. pneumoniae or Haemophilus influenzae in mice, telithromycin was more effective than clarithromycin and comparable to azithromycin...
  60. pmc Telithromycin-resistant Streptococcus pneumoniae
    Fred Goldstein
    Emerg Infect Dis 11:1489-90. 2005
  61. ncbi Risk of hepatotoxicity associated with the use of telithromycin: a signal detection using data mining algorithms
    Yan Chen
    Division of Pharmacy Practice and Administrative Sciences, James L Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH 45267, USA
    Ann Pharmacother 42:1791-6. 2008
    ..With the exception of case reports, limited data are available regarding the risk of hepatotoxicity associated with the use of telithromycin...
  62. ncbi Selection of resistance of telithromycin against Haemophilus influenzae, Moraxella catarrhalis and streptococci in comparison with macrolides
    Lorenzo Drago
    Laboratory of Clinical Microbiology, Department of Clinical Sciences L Sacco Teaching Hospital, University of Milan, Via GB Grassi 74, 20157 Milan, Italy
    J Antimicrob Chemother 54:542-5. 2004
    ..The in vitro abilities of telithromycin, azithromycin and clarithromycin to select for resistance were compared by testing isolates of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae and beta-haemolytic streptococci...
  63. pmc Diversity of ribosomal mutations conferring resistance to macrolides, clindamycin, streptogramin, and telithromycin in Streptococcus pneumoniae
    Annie Canu
    UFR des Sciences Pharmaceutiques, Caen, France
    Antimicrob Agents Chemother 46:125-31. 2002
    ..In six remaining mutants, no mutations in L22, L4, or 23S rRNA could be detected...
  64. ncbi Kinetic bactericidal activity of telithromycin, azithromycin and clarithromycin against respiratory pathogens
    L Drago
    Laboratory of Clinical Microbiology, Department of Clinical Sciences L Sacco, University of Milan, Italy
    APMIS 113:655-63. 2005
    ..In conclusion, telithromycin proved to possess bactericidal activity against a wide range of respiratory pathogens, including strains resistant to common macrolides...
  65. pmc Ketolide antimicrobial activity persists after disruption of interactions with domain II of 23S rRNA
    Guy W Novotny
    Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK 5230 Odense M, Denmark
    Antimicrob Agents Chemother 48:3677-83. 2004
    b>Ketolides are the latest derivatives developed from the macrolide erythromycin to improve antimicrobial activity...
  66. ncbi Streptococcus pyogenes isolates with characterized macrolide resistance mechanisms in Spain: in vitro activities of telithromycin and cethromycin
    María Isabel Morosini
    Servicio de Microbiologia, Hospital Universitario Ramon y Cajal, Ctra de Colmenar, Km 9, 1, 28034 Madrid, Spain
    J Antimicrob Chemother 52:50-5. 2003
    ..6%) or mef(A) plus erm(B) (4.2%) was also observed. Both ketolides displayed a significant in vitro activity against S. pyogenes regardless of the macrolide resistance mechanisms...
  67. pmc Telithromycin- and fluoroquinolone-resistant Streptococcus pneumoniae in Taiwan with high prevalence of resistance to macrolides and beta-lactams: SMART program 2001 data
    Po Ren Hsueh
    Departments of Laboratory Medicine and Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
    Antimicrob Agents Chemother 47:2145-51. 2003
    ..However, the occurrence of telithromycin resistance is impressive and raises concerns for the future...
  68. pmc In vitro activity of the new ketolide telithromycin compared with those of macrolides against Streptococcus pyogenes: influences of resistance mechanisms and methodological factors
    P Bemer-Melchior
    Department of Microbiology, Laennec University Hospital, Nantes, France
    Antimicrob Agents Chemother 44:2999-3002. 2000
    ..The effect of 5 to 6% CO(2) was remarkable on resistant strains, by increasing MICs of telithromycin from 1 to 6 twofold dilutions against D-E- and F-group isolates...
  69. ncbi Overcoming antimicrobial resistance: profile of a new ketolide antibacterial, telithromycin
    R Leclercq
    CHU de Caen, Service de Microbiologie, Avenue Cote de Nacre, 14033 Caen Cedex, France
    J Antimicrob Chemother 48:9-23. 2001
    ..Telithromycin is the first of a new family of antibacterials--the ketolides--and has been designed specifically for the treatment of community-acquired respiratory tract infections (RTIs)...
  70. pmc Activities of cethromycin and telithromycin against recent North American isolates of Streptococcus pneumoniae
    James H Jorgensen
    Department of Pathology, University of Texas Health Science Center, San Antonio, Texas, USA
    Antimicrob Agents Chemother 48:605-7. 2004
    The in vitro activities of two investigational ketolides, cethromycin (formerly ABT-773) and telithromycin, were determined for a selected group of 312 Streptococcus pneumoniae isolates from a national surveillance program...
  71. pmc Comparative activities of telithromycin (HMR 3647), levofloxacin, and other antimicrobial agents against human mycoplasmas
    C M Bebear
    Laboratoire de Bacteriologie, Universite Victor Segalen Bordeaux 2, 33076 Bordeaux Cedex, France
    Antimicrob Agents Chemother 44:1980-2. 2000
    ..Telithromycin MICs of </=0.25 microgram/ml were found for all isolates, except for Mycoplasma hominis, while levofloxacin was active at concentrations of </=1 microgram/ml against all species studied...
  72. ncbi Ketolides: new antimicrobials for community-acquired pneumonia
    Patricia J Neafsey
    Home Healthc Nurse 23:141-3. 2005
  73. ncbi Intrapulmonary concentrations of telithromycin: clinical implications for respiratory tract infections due to Streptococcus pneumoniae
    C T Ong
    Center for Anti Infective Research and Development, Hartford Hospital, CT 06102, USA
    Chemotherapy 51:339-46. 2005
    ..To assess the bronchopulmonary drug disposition of a novel ketolide, telithromycin (TEL), the epithelial lining fluid (ELF) and alveolar macrophage (AM) concentrations were utilized as a surrogate marker for lung penetration...
  74. ncbi Clinical use of antimicrobial pharmacodynamic profiles to optimise treatment outcomes in community-acquired bacterial respiratory tract infections: application to telithromycin
    David P Nicolau
    Center for Anti Infective Research and Development, Hartford Hospital, Hartford, CT 06102 5037, USA
    Expert Opin Pharmacother 5:229-35. 2004
    ..Telithromycin possesses pharmacodynamic characteristics that make this novel ketolide an optimal choice for the empirical management of community-acquired respiratory tract infections...
  75. pmc Expression of the mef(E) gene encoding the macrolide efflux pump protein increases in Streptococcus pneumoniae with increasing resistance to macrolides
    Aleksandra K Wierzbowski
    Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
    Antimicrob Agents Chemother 49:4635-40. 2005
    ..In conclusion, increased expression of mef(E) is associated with higher levels of macrolide resistance in macrolide-resistant S. pneumoniae...
  76. pmc Influence of carbon dioxide on the MIC of telithromycin for Streptococcus pneumoniae: an in vitro-in vivo study
    Eric Batard
    Laboratoire d Antibiologie, UER de Medecine, 1 rue Gaston Veil, 44035 Nantes Cedex 01, France
    Antimicrob Agents Chemother 49:464-6. 2005
    ..2% of 346 Streptococcus pneumoniae ermB-positive strains. An increased telithromycin MIC in CO(2) was not correlated with loss of its activity in the murine sepsis/peritonitis model...
  77. ncbi In vitro activity of new ketolides against macrolide-susceptible and -resistant Staphylococcus aureus isolates with defined resistance gene status
    Franz Josef Schmitz
    J Antimicrob Chemother 49:580-2. 2002
  78. pmc Pharmacodynamic activity of telithromycin at simulated clinically achievable free-drug concentrations in serum and epithelial lining fluid against efflux (mefE)-producing macrolide-resistant Streptococcus pneumoniae for which telithromycin MICs vary
    George G Zhanel
    Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
    Antimicrob Agents Chemother 49:1943-8. 2005
    ..In conclusion, free-telithromycin concentrations in serum and ELF simulating C(max)/MIC > or = 3.5 and AUC(0-24 h)/MIC > or = 25 completely eradicated (> or =4 log(10) killing) macrolide-resistant S. pneumoniae at 24 and 48 h...
  79. ncbi In vitro activities of new ketolide, telithromycin, and eight other macrolide antibiotics against Streptococcus pneumoniae having mefA and ermB genes that mediate macrolide resistance
    Kimiko Ubukata
    Laboratory of Infectious Agents Surveillance, Kitasato Institute for Life Sciences, Kitasato University, 5 9 1 Sirokane, Minato ku, Tokyo 108 8641, Japan
    J Infect Chemother 9:221-6. 2003
    ..Most strains having the mefA and ermB genes were serotyped to 3, 6, 14, 19, and 23. These results suggest that TEL may be a useful chemotherapeutic agent for respiratory tract infections caused by S. pneumoniae...
  80. ncbi Effects of macrolides and ketolides on mycobacterial infections
    Luiz E Bermudez
    Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA
    Curr Pharm Des 10:3221-8. 2004
    ..b>Ketolides are a semi-synthetic derivative of erythromycin A, which differs from erythromycin A by substitution of a 3-keto ..
  81. pmc Antipneumococcal activities of a ketolide (HMR 3647), a streptogramin (quinupristin-dalfopristin), a macrolide (erythromycin), and a lincosamide (clindamycin)
    A L Barry
    The Clinical Microbiology Institute, Wilsonville, Oregon 97070, USA
    Antimicrob Agents Chemother 42:945-6. 1998
    ....
  82. pmc In vitro activity of the ketolide HMR 3647 (RU 6647) for Legionella spp., its pharmacokinetics in guinea pigs, and use of the drug to treat guinea pigs with Legionella pneumophila pneumonia
    P H Edelstein
    Departments of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 4283, USA
    Antimicrob Agents Chemother 43:90-5. 1999
    ..HMR 3647 is effective against L. pneumophila in vitro, in infected macrophages, and in a guinea pig model of Legionnaires' disease. HMR 3647 given once daily should be evaluated as a treatment for Legionnaires' disease in humans...
  83. pmc In vitro activities of the novel ketolide telithromycin (HMR 3647) against erythromycin-resistant Streptococcus species
    J Jalava
    Antimicrobial Research Laboratory, National Public Health Institute, Turku, Finland
    Antimicrob Agents Chemother 45:789-93. 2001
    ..008 to 0.25 microg/ml). Our in vitro data show that for S. pyogenes strains which constitutively express the erm(B) methylase gene, MICs are so high that the strains might be clinically resistant to telithromycin...
  84. ncbi In vitro activity of telithromycin, a new ketolide, against Chlamydia pneumoniae
    N Miyashita
    Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama 701 0192, Japan
    J Antimicrob Chemother 48:403-5. 2001
    ..These results appear to indicate that telithromycin is an effective antibiotic that should play some role in the treatment of respiratory tract infections caused by C. pneumoniae...
  85. ncbi Comparative in vitro activity of telithromycin (HMR 3647), three macrolides, amoxycillin, cefdinir and levofloxacin against gram-positive clinical isolates in Japan
    H Okamoto
    Department of Microbiology, Toho University School of Medicine, Omori Nishi, Ota ku, Tokyo, Japan
    J Antimicrob Chemother 46:797-802. 2000
    ..Against erythromycin A-susceptible or inducibly resistant Staphylococcus aureus and erythromycin A-susceptible and intermediate Enterococcus faecalis, telithromycin was highly active...
  86. ncbi Telithromycin: a new ketolide antimicrobial for treatment of respiratory tract infections
    H M Yassin
    VA New Jersey Health Care System, East Orange, NJ and UMDNJ, New Jersey Medical School, Newark, NJ, USA
    Expert Opin Investig Drugs 10:353-67. 2001
    ..The most common adverse events were diarrhoea, nausea, headache and dizziness. Telithromycin should provide an effective, convenient and well-tolerated once-daily oral therapy for treatment of respiratory infections...
  87. ncbi Activity of telithromycin, a new ketolide antibacterial, against atypical and intracellular respiratory tract pathogens
    M R Hammerschlag
    Division of Infectious Diseases, Department of Pediatrics, Box 49, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203 2098, USA
    J Antimicrob Chemother 48:25-31. 2001
    ..Telithromycin (HMR 3647) is the first of a new family of antibacterials, the ketolides, and has been designed specifically for the treatment of community-acquired respiratory tract infections (RTIs)...
  88. ncbi Lung concentrations of telithromycin after oral dosing
    O A Khair
    Department of Medical Microbiology, City Hospital NHS Trust, Birmingham B18 7QH, UK
    J Antimicrob Chemother 47:837-40. 2001
    ..03 mg/L), as well as the atypical microorganism Mycoplasma pneumoniae (0.001 mg/L), and suggest that telithromycin may be effective for the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease...
  89. pmc In vitro pharmacodynamics of the new ketolides HMR 3004 and HMR 3647 (Telithromycin) against Chlamydia pneumoniae
    I Gustafsson
    Departments of Infectious Diseases, University Hospital, Uppsala, Sweden
    Antimicrob Agents Chemother 44:1846-9. 2000
    The ketolides HMR 3004 and HMR 3647 (telithromycin) are a new class of macrolides that have a potential clinical efficacy against intracellular pathogens...
  90. ncbi Antibacterial effect of telithromycin (HMR 3647) and comparative antibiotics against intracellular Legionella pneumophila
    A L Baltch
    Infectious Disease Section, Stratton VA Medical Center and Albany Medical College, NY 12208, USA
    J Antimicrob Chemother 46:51-5. 2000
    ..In conclusion, the ketolide telithromycin has excellent activity against intracellular L. pneumophila strain L-1033 and should be evaluated for therapy of legionnaires' disease...
  91. pmc In vitro activities of the ketolides telithromycin (HMR 3647) and HMR 3004 compared to those of clarithromycin against slowly growing mycobacteria at pHs 6.8 and 7.4
    N Rastogi
    Unite de la Tuberculose et des Mycobacteries, Institut Pasteur, 97165 Pointe à Pitre Cedex, Guadeloupe
    Antimicrob Agents Chemother 44:2848-52. 2000
    The in vitro activities of HMR 3647 (telithromycin) and HMR 3004, two novel semisynthetic ketolides, were investigated and compared with that of the reference macrolide drug, clarithromycin, against 34 strains of slowly growing ..
  92. ncbi Efficacy and tolerability of once-daily telithromycin compared with high-dose amoxicillin for treatment of community-acquired pneumonia
    L Hagberg
    Dept of Infectious Diseases, Sahlgrenska University Hospital, Goteborg, Sweden
    Infection 30:378-86. 2002
    ..This randomized, double-blind study compared the efficacy and tolerability of the new ketolide antimicrobial telithromycin with that of high-dose amoxicillin in the treatment of community-acquired pneumonia (CAP)...
  93. ncbi Macrolide-resistance mechanisms in Streptococcus pneumoniae isolates from Belgium
    J Van Eldere
    Department of Microbiology and Immunology, Katholieke Universiteit Leuven, Leuven, Belgium
    Clin Microbiol Infect 11:332-4. 2005
    ..No difference in the prevalence of different resistance mechanisms was observed compared to isolates collected in 1995-1997...
  94. ncbi In vitro activity of the new ketolide ABT-773 against community acquired respiratory tract isolates and Viridans Streptococci
    Jose Maria Casellas
    Centro de Estudios en Antimicrobianos, Buenos Aires, Argentina
    Diagn Microbiol Infect Dis 42:107-12. 2002
    ..ABT-773 exerted bactericidal activity against selected isolates of S. pneumoniae, M. catarrhalis and H. influenzae, however, it was only bacteriostatic against methicillin-susceptible S. aureus...
  95. ncbi PROTEKT years 1-3 (1999-2002): study design and methodology
    I Harding
    The Micron Group, Marmont Priory Farm, Upwell, Wisbech, Cambridgeshire PE14 9AR, UK
    J Chemother 16:9-18. 2004
  96. pmc Susceptibility to telithromycin in 1,011 Streptococcus pyogenes isolates from 10 central and Eastern European countries
    Kensuke Nagai
    Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033, USA
    Antimicrob Agents Chemother 46:546-9. 2002
    ..3% of strains. Erm(A) [subclass erm(TR)] was most commonly encountered (60.5%), followed by mef(A) (23.4%) and erm(B) (14.5%). At <0.5 microg/ml, telithromycin was active against 98.5% of the strains tested...
  97. ncbi [Molecular analytical evaluation of macrolide- and ketolide-resistant Streptococcus pneumoniae--mechanism of action of telithromycin and resistance to it]
    Matsuhisa Inoue
    Department of Microbiology, Kitasato University School of Medicine
    Jpn J Antibiot 57:425-37. 2004
    ..actions of TEL were considered to be derived from its novel chemical structure and might be characteristics of ketolides not possessed by macrolides. In the survey of PROTEKT in 1999 to 2002, among 13,864 strains of S...
  98. ncbi Activity of telithromycin against 26 quinolone-resistant pneumococci with known quinolone-resistance mechanisms
    K Nagai
    Department of Pathology, Hershey Medical Center, Hershey, PA 17033, USA
    Clin Microbiol Infect 7:703-5. 2001
    ..Ciprofloxacin MICs (mg/L) were 8-64 compared to 1-32 (levofloxacin), 0.5 . or = 32 (sparfloxacin) and 0.125-4 (moxifloxacin). Telithromycin MIC50 and MIC90 values (mg/L) were 0.016 and 0.25, with only one strain having an MIC of 2 mg/L...
  99. pmc In vitro activities of novel 2-fluoro-naphthyridine-containing ketolides
    Darren Abbanat
    Johnson and Johnson Pharmaceutical Research and Development, L L C, Raritan, NJ 08869, USA
    Antimicrob Agents Chemother 49:309-15. 2005
    In vitro activities of erythromycin A, telithromycin, and two investigational ketolides, JNJ-17155437 and JNJ-17155528, were evaluated against clinical bacterial strains, including selected common respiratory tract pathogens...
  100. pmc Binding site of the bridged macrolides in the Escherichia coli ribosome
    Liqun Xiong
    Center for Pharmaceutical Biotechnology, University of Illinois, 900 S Ashland Ave, Chicago, IL 60607, USA
    Antimicrob Agents Chemother 49:281-8. 2005
    b>Ketolides represent the latest group of macrolide antibiotics. Tight binding of ketolides to the ribosome appears to correlate with the presence of an extended alkyl-aryl side chain...
  101. pmc Pharmacodynamic profile of telithromycin against macrolide- and fluoroquinolone-resistant Streptococcus pneumoniae in a neutropenic mouse thigh model
    Pamela R Tessier
    Center for Anti Infective Research and Development, Hartford Hospital, 80 Seymour St, Hartford, CT 06102 5037, USA
    Antimicrob Agents Chemother 49:188-94. 2005
    ..pneumoniae strains and bacterial inhibition (stasis) of telithromycin were predicted by ratios of the AUC for the free drug concentration/MIC of approximately 1,000 and 200, respectively...

Research Grants24

  1. Mechanism of Induction of erm Genes By Ketolide Antibiotics
    Nora Vazquez Laslop; Fiscal Year: 2010
    ..However, recent data have shown that ketolides do induce expression of ermC...
  2. Assembly Properties of the 50S Ribosomal Subunit Under Pertubation Conditions
    Michael Sykes; Fiscal Year: 2009
    ..Additionally, Lincosamides, ketolides and streptogramin B antibiotics have each been shown to specifically inhibit assembly of the large subunit in E...
  3. GENERATION OF KETOLIDES BY COMBINATORIAL BIOSYNTHESIS
    Yongquan Xue; Fiscal Year: 1999
    ..venezuelae through which pikromycin analogues can be generated rapidly and systematically; and 2) generate novel ketolides by creating a 'hybrid biosynthetic pathway that combines the pikromycin polyketide synthase (PikA) with a ..
  4. ENGINEERED BIOSYNTHESIS OF NOVEL KETOLIDE ANTIBIOTICS
    Kevin Reynolds; Fiscal Year: 2000
    ..PROPOSED COMMERCIAL APPLICATIONS: Ketolides hold promise as a solution to the increase in erythromycin- resistant bacterial pathogens, including ..
  5. Macrolide Discovery through Glycosylation
    Alex Romero; Fiscal Year: 2006
    ..development and the potential for cross-resistance between our lead compounds and other leading macrolides/ketolides, an important criteria for assessing a compound's future marketability...
  6. ANTIBIOTIC INHIBITION OF BACTERIAL RIBOSOME FORMATION
    WILLIAM CHAMPNEY; Fiscal Year: 2002
    ..This investigation will explore the new observation that macrolide antibiotics as well as the ketolides, lincosamides, streptogramin B compounds and oxazolidinones can all inhibit the assembly of the large ribosomal ..
  7. Molecular Epidemiology, Virulence, and Genomic Characterization of Ureaplasmas
    Ken B Waites; Fiscal Year: 2010
    ....
  8. BIOCHEMISTRY AND MOLECULAR GENETICS OF MITOMYCIN BIOSYNT
    David Sherman; Fiscal Year: 2003
    ..Overall, this work will provide an important theoretical and experimental base for future combinatorial biology-based production of novel AHBA-derived natural products using molecular genetic technology. ..
  9. Leptomycin B Development for Cancer Therapy
    Charles Hutchinson; Fiscal Year: 2004
    ..coelicolor, we will proceed with preclinical development of LMB or the discovery and development of an LMB analog in Phase II research. ..
  10. RIBOSOMAL PEPTIDYL TRANSFERASE CENTER
    Alexander Mankin; Fiscal Year: 2003
    ..Understanding structure and function of the main catalytic center of the ribosome is indispensable for the rational design of new antibiotics and overcoming mechanisms of drug resistance. ..
  11. DM1-Monoclonal Antibody Conjugates
    Charles Hutchinson; Fiscal Year: 2002
    ..Therefore, a successful outcome of our research would meet the needs for preclinical and clinical development at a far lower cost than the current DM1 synthesis that is the only source of this cytotoxin. ..
  12. Genomic Analysis of Antibiotic Biosynthesis
    David Sherman; Fiscal Year: 2005
    ..coelicolor genome. ..
  13. New mechanism of resistance to oxazolidinone antibiotics in Staphylococcus aureus
    Alexander S Mankin; Fiscal Year: 2010
    ....
  14. New Ketolide Antibacterial Drugs
    Charles Hutchinson; Fiscal Year: 2005
    ..A have excellent in vitro and in vivo antibacterial activity, comparable to or better than the leading ketolides in current clinical trials or approved by the FDA for specific uses...
  15. Novel Geldanamycin Analogs as Anti-tumor Agents
    Gary Ashley; Fiscal Year: 2005
    ..By these studies, we will identify the best geldanamycin analog to carry forward into drug development, with the eventual aim of filing and IND application and performing clinical trials. ..
  16. Antibiotic Hypersusceptibility Mutations in Bacteria
    Alexander Mankin; Fiscal Year: 2005
    ..In addition to identifying promising targets for potentiators, the project will help unravel new aspects of the mechanism of action of antibiotics and new features of bacterial physiology. ..
  17. COMBINATORIAL BIOSYNTHESIS AND THE PIKROMYCIN PATHWAY
    David Sherman; Fiscal Year: 2002
    ....
  18. HAEMOPHILUS ANTIGEN REGULATION OF INFLAMMATION IN COPD
    Sanjay Sethi; Fiscal Year: 2003
    ..Identification of the integral bacterial and host components that contribute to immune-mediated inflammation in COPD will ultimately lead to novel therapeutic strategies to alter disease progression and improve outcome in COPD. ..
  19. Laulimalide Production Genes
    Charles Hutchinson; Fiscal Year: 2003
    ..Success will lead to development of a fermentation-based process to make large amounts of laulimalide or one of its analogs for preclinical studies as an antitumor drug. ..
  20. Discodermolide Biosynthesis Genes
    Charles Hutchinson; Fiscal Year: 2002
    ..Our research will also establish the technological base for a general approach to making many other currently scarce marine polyketides with anti-tumor activity available in large amounts for drug development. ..
  21. MYCOBACTERIAL ENVIRONMENT WITHIN MACROPHAGES
    Luiz Bermudez; Fiscal Year: 2003
    ..We believe that the proposed studies will generate important information about the phagosome environment and the mycobacterial response to it. ..
  22. Innate Immunity and exacerbations of COPD
    Sanjay Sethi; Fiscal Year: 2009
    ..The overall goal of this research is to identify specific aspects of the innate defense of the lung that determine the frequency of exacerbations in COPD that will serve as potential therapeutic targets to reduce exacerbations. ..
  23. CRYSTALLOGRAPHIC STUDIES ON RIBOSOMAL PARTICLES
    ADA E YONATH; Fiscal Year: 2010
    ..These studies have already illuminated principles of drug selectivity, and provided significant basic knowledge of possible pathways of drug resistance, hence paving the way to improve therapeutic properties. ..
  24. Post Translation Regulation in Mycobacteria
    Luiz Bermudez; Fiscal Year: 2008
    ..In case we confirm our hypothesis, future work will address the role of Ion in M. tuberculosis [unreadable] [unreadable] [unreadable]..