We investigated the in vitro postantibiotic effects (PAEs) of the ketolides telithromycin (HMR 3647) and HMR 3004 and analyzed the results using the sigmoid E(max) model. Mean maximum telithromycin PAEs against erythromycin A-susceptible strains of Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae were 3. 7, 8.9, and 9.7 h, respectively, while maximum PAEs for erythromycin A-resistant strains were much shorter. Mean maximum HMR 3004 PAEs were 3.2 to 4.4 h for all species.
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http://dx.doi.org/10.1128/AAC.44.6.1749-1753.2000 | DOI Listing |
Afr Health Sci
December 2015
School of Anatomical Sciences, University of Witswatersrand (Wits), South Africa.
Background: Malaria is on the increase due to emergence of parasite drug resistance and there is thus an urgent need for the development of new antiparasitic drugs effective at low concentrations. Ketolides antibiotics are used for treatment of various ailments and are relevant candidates to establish antiparasitic activity.
Objectives: The present study investigates the activity of ketolide compounds HMR 3004 and HMR 3647 (telithromycin) (0.
Antimicrob Agents Chemother
October 2004
Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark.
Ketolides are the latest derivatives developed from the macrolide erythromycin to improve antimicrobial activity. All macrolides and ketolides bind to the 50S ribosomal subunit, where they come into contact with adenosine 2058 (A2058) within domain V of the 23S rRNA and block protein synthesis. An additional interaction at nucleotide A752 in the rRNA domain II is made via the synthetic carbamate-alkyl-aryl substituent in the ketolides HMR3647 (telithromycin) and HMR3004, and this interaction contributes to their improved activities.
View Article and Find Full Text PDFAntimicrob Agents Chemother
April 2004
INSERM U479, CHU Xavier Bichat, 75018, Paris, France.
A classical velocity centrifugation technique was used to study the in vitro uptake of the new ketolide ABT-773 by human polymorphonuclear neutrophils (PMNs) and a myelomonoblastic cell line, PLB-985, which can be differentiated into PMNs under certain culture conditions, compared to that of HMR 3004. ABT-773 was rapidly taken up by PMNs (cellular concentration to extracellular concentration ratio [C/E], about 34 at 30 s and up to 207 at 5 min), and uptake plateaued from 30 to 180 min (C/E, about 300). ABT-773 was accumulated significantly better than HMR 3004 from 5 to 180 min.
View Article and Find Full Text PDFJ Chemother
August 2003
Faculté des Sciences 1, Ain Chock, BP 5366, Maarif, Casablanca, Morocco.
Interactions between antibacterial agents and polymorphonuclear neutrophils (PMNs) are a major focus of investigation. Owing to the variable drug susceptibility of PMNs from different individuals, in vitro studies require samples from large panels of healthy volunteers to reach statistical significance. Here, we used a phagocytic cell line, PLB-985, which can differentiate into mature PMNs in vitro, for the study of cellular interactions (drug uptake and antioxidant effects) of two macrolides (azithromycin and roxithromycin) and four ketolides [HMR 3004, HMR 3647 (telithromycin), HMR 3562 and HMR 3787].
View Article and Find Full Text PDFAntimicrob Agents Chemother
June 2002
Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark.
Methylation of specific nucleotides in rRNA is one of the means by which bacteria achieve resistance to macrolides-lincosamides-streptogramin B (MLS(B)) and ketolide antibiotics. The degree of resistance is determined by how effectively the rRNA is methylated. We have implemented a bacterial system in which the rRNA methylations are defined, and in this study we investigate what effect Erm mono- and dimethylation of the rRNA has on the activity of representative MLS(B) and ketolide antibiotics.
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