Drugs online research references
Antimicrob Agents Chemother. 2002 Sep;46(9):3054-6.
Clinical isolates of Staphylococcus aureus with ribosomal mutations conferring resistance to macrolides.
Prunier AL, Malbruny B, Tande D, Picard B, Leclercq R.
Service de Microbiologie, CHU Cote de Nacre, Caen, France.
Six strains of Staphylococcus aureus isolated from cystic fibrosis patients after treatment with azithromycin were cross-resistant to azithromycin and erythromycin. None of the isolates contained erm or msr(A) genes, but they all carried either A2058G/U or A2059G mutations within the rrl genes, with a majority of the rRNA copies bearing the mutation. One strain displayed an additional mutation in the rplV gene, encoding the L22 ribosomal protein.
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J Periodontal Res. 2002 Aug;37(4):250-4.
Quantitative comparison of the cytocidal effect of seven macrolide antibiotics on human periodontal ligament fibroblasts.
Maizumi N, Tamura Y, Kanai H, Tsutsui T.
Department of Pharmacology, The Nippon Dental University, School of Dentistry at Tokyo, Tokyo, Japan.
The cytocidal effect of seven macrolide antibiotics on human periodontal ligament fibroblasts (Pel cells) was studied. Pel cells were exposed for 48 h to erythromycin (EM), clarithromycin (CAM), roxithromycin (RXM), azithromycin (AZM), josamycin (JM), midecamycin (MDM), and rokitamycin (RKM), and allowed to form colonies. The cytocidal effect of the macrolides was measured as a decrease in colony-forming efficiency and was found to increase with the concentration. To obtain a quantitative measure of the cytocidal effect, the LD50, i.e. the concentration that decreases colony-forming efficiency 50% relative to control cells, was extrapolated from the concentration-response curves. The rank of the macrolides according to their cytocidal effect (LD50) was RKM > RXM > CAM > AZM > JM > MDM approximately EM. RKM, RXM, CAM, AZM, and JM were at least 1.7-12.2 times more cytocidal than MDM or EM. When extrapolated from the concentration-response curves, the relative survival of the Pel cells exposed to each of the macrolides at the MIC90 concentrations for periodontopathic bacteria was estimated to be: > or = 53.8% for RKM, > or = 92.7% for RXM, > or = 94.6% for CAM, > or = 97.1% for AZM, and > or = 86.2% for EM. The effect of the antibiotics on the mRNA expression of alkaline phosphatase (ALP) and type I procollagen (COL) was examined in Pel cells exposed for 48 h to RXM, CAM, AZM, and EM, which exhibited strong, moderate, and weak cytocidal activity. The constitutive levels of both ALP and COL mRNA were retained in cells exposed to RXM at < or = 3 microM, CAM at < or = 10 microM, and AZM or EM at < or = 3 microM. The MIC90 against periodontopathic bacteria is < or = 4.8 microM for RXM, 5.3 microM for CAM, 2.7 microM for AZM, and 21.8 microM for EM. These results suggest that topical administration of CAM or AZM to the gingival crevice at their MIC90 concentration for periodontopathic bacteria would have little adverse effect on the growth and differentiation of the periodontal ligament. It is important to note, however, that these findings have yet to be extrapolated to in vivo conditions.
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Pharmacol Res. 2002 Jul;46(1):95-100.
Improved tonsillar disposition of azithromycin following a 3-day oral treatment with 20 mg kg(-1) in paediatric patients.
Baschiera F, Fornai M, Lazzeri G, Blandizzi C, Bruschini P, del Tacca M.
Division of Pharmacology and Chemotherapy, Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, Italy.
The present study was performed in order to compare azithromycin concentrations in tonsils of paediatric patients treated with different dose regimens of this antibiotic. Sixty-four children, scheduled to undergo surgical removal of tonsils, were treated with azithromycin 10 or 20 mgkg(-1) daily as oral suspension for 3 days. Samples of blood and tonsil were collected during surgery at days 0.5, 2.5, 4.5, 6.5 or 8.5 after the last dose. Azithromycin concentrations were measured by reversed phase high-performance liquid chromatography. In patients treated with 10 mgkg(-1), the highest concentrations of azithromycin were detected in plasma and tonsils at day 0.5 and 2.5, respectively. Consistent drug levels could be measured in tonsils up to 8.5 days. After administration of 20 mgkg(-1), azithromycin tonsillar concentrations were higher than those obtained with 10 mgkg(-1) up to day 6.5, whereas plasma levels did not differ significantly. The present results indicate that an improved tonsillar distribution of azithromycin can be achieved when this antibiotic is administered for 3 days at doses higher than 10 mgkg(-1) daily. These findings give pharmacokinetic support to the suggestion that increments of azithromycin dosing might ensure enhanced therapeutic levels at infective sites of the upper respiratory tract.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12208127&dopt=Abstract
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