Drugs online research references
Acta Trop. 2001 Sep 1;80(1):39-44.
Antimalarial activity of azithromycin, artemisinin and dihydroartemisinin in fresh isolates of Plasmodium falciparum in Thailand.
Noedl H, Wernsdorfer WH, Krudsood S, Wilairatana P, Kollaritsch H, Wiedermann G, Looareesuwan S.
Department of Specific Prophylaxis and Tropical Medicine, Institute of Pathophysiology, University of Vienna, Kinderspitalgasse 15, A-1095, Vienna, Austria.
Antibiotics with antimalarial activity may offer an interesting alternative for the treatment of multidrug-resistant falciparum malaria. Azithromycin, a relatively recent semisynthetic derivative of erythromycin, was tested for its in vitro activity against fresh isolates of Plasmodium falciparum. As the reportedly slow onset of action of azithromycin suggests its combination with fast-acting substances, such as artemisinin-derivatives, dihydroartemisinin (DHA) was tested parallel as a possible combination partner. The effective concentrations found for azithromycin in this study (EC(50) = 29.3 micromol/l, EC(90) = 77.1 micromol/l blood medium mixture (BMM)) are comparable to those of other antimalarials in the antibiotics class and are considerably higher than those found for mefloquine or quinine. The absence of an activity correlation between azithromycin and chloroquine, quinine and artemisinin emphasises the independence of azithromycin drug response from the sensitivity to these drugs. A weak activity correlation (rho(EC90) = 0.352; p = 0.028), which could point to a potential cross-sensitivity but is probably of little clinical importance, was found with mefloquine above the EC(50) level. Provided that further clinical trials support the combination of these drugs, DHA may offer an interesting combination partner for azithromycin owing to its rapid onset of action and the comparatively low effective concentrations (EC(50) = 1.65 nmol/l, EC(90) = 7.10 nmol/l BMM). This combination may serve as an interesting alternative for tetracycline and doxycycline, which cannot be used in pregnant women and children, and exhibit phototoxicity. Nevertheless, the relatively high cost of this combination, as well as the controversial reports of the clinical efficacy, may limit the usefulness of azithromycin in malaria therapy and require an adjustment of previously used treatment regimens.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11495642&dopt=Abstract
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facm.ucl.ac.be
The dicationic macrolide antibiotic azithromycin inhibits the uptake of horseradish peroxidase (HRP) by fluid-phase pinocytosis in fibroblasts in a time- and concentration-dependent fashion without affecting its decay (regurgitation and/or degradation). The azithromycin effect is additive to that of nocodazole, known to impair endocytic uptake and transport of solutes along the endocytic pathway. Cytochemistry (light and electron microscopy) shows a major reduction by azithromycin in the number of HRP-labeled endocytic vesicles at 5 min (endosomes) and 2 h (lysosomes). Within 3 h of exposure, azithromycin also causes the appearance of large and light-lucentlelectron-lucent vacuoles, most of which can be labeled by lucifer yellow when this tracer is added to culture prior to azithromycin exposure. Three days of treatment with azithromycin result in the accumulation of very large vesicles filled with pleiomorphic content, consistent with phospholipidosis. These vesicles are accessible to fluorescein-labeled bovine serum albumin (FITC-BSA) and intensively stained with filipin, indicating a mixed storage with cholesterol. The impairment of HRP pinocytosis directly correlates with the amount of azithromycin accumulated by the cells, but not with the phospholipidosis induced by the drug. The proton ionophore monensin, which completely suppresses azithromycin accumulation, also prevents inhibition of HRP uptake. Erythromycylamine, another dicationic macrolide, also inhibits HRP pinocytosis in direct correlation with its cellular accumulation and is as potent as azithromycin at equimolar cellular concentrations. We suggest that dicationic macrolides inhibit fluid-phase pinocytosis by impairing the formation of pinocytic vacuoles and endosomes.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11499789&dopt=Abstract
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uottawa.ca
BACKGROUND: The percentage of Neisseria gonorrhoeae isolates resistant to antimicrobial agents commonly used for treatment is unknown in many Caribbean countries. GOAL: To determine the antimicrobial susceptibility of N gonorrhoeae isolates from Trinidad (144 isolates), Guyana (70 isolates), and St. Vincent (68 isolates) so baseline data can be established for further studies, and to assist in establishing effective treatment guidelines. STUDY DESIGN: Consecutive urethral and endocervical specimens from several clinics were collected and identified as N gonorrhoeae. Isolates of N gonorrhoeae were tested for their susceptibility to penicillin, tetracycline, ceftriaxone, ciprofloxacin, spectinomycin, and azithromycin. The presumptive identification of penicillinase-producing N gonorrhoeae and/or tetracycline-resistant N gonorrhoeae isolates based on MIC was confirmed by plasmid and tetM content analysis. RESULTS: High percentages of penicillin and/or tetracycline resistance were observed in N gonorrhoeae isolates from Guyana (92.9%), St. Vincent (44.1%), and Trinidad (42.4%). Isolates from all three countries were susceptible to ceftriaxone, ciprofloxacin, and spectinomycin. One penicillinase-producing N gonorrhoeae/tetracycline-resistant N gonorrhoeae from Guyana had an MIC of 0.5 microg/l to ciprofloxacin. This and nine other isolates from Guyana also were resistant to azithromycin (defined as MIC > or = 2.0 microg/ml) as well as penicillin and tetracycline. A reduced susceptibility to azithromycin was displayed by 16% of the isolates from St. Vincent and 72% of the isolates from Guyana (MIC, 0.25-1.0 microg/ml). Most penicillinase-producing N gonorrhoeae isolates carried Africa-type plasmids (61/90), with 28 of 90 having Toronto-type plasmids and a single isolate carrying an Asia-type plasmid. The tetM determinant in tetracycline-resistant N gonorrhoeae isolates was predominantly of the Dutch type (68/91). CONCLUSIONS: The high prevalence of N gonorrhoeae isolates from 3 of 21 English- and Dutch-speaking Caricom countries in the Caribbean with either plasmid-mediated or chromosomal resistance to penicillin and tetracycline supports international observations that these drugs should not be used to treat gonococcal infections. The detection of isolates with reduced susceptibility to drugs such as azithromycin, which currently are recommended for treatment in the region, attest to the importance of the continued monitoring of gonococcal antimicrobial susceptibility for the maintenance of effective treatment guidelines.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11518867&dopt=Abstract
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