Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dirithromycin is a 9-N-11-O-oxazine derivative which is formed by condensation of 9(S)-erythromycylamine with 2-(2-methoxyethoxy)acetaldehyde. Dirithromycin is hydrolyzed, either under acidic conditions or in vivo, to its major active metabolite, 9(S)-erythromycylamine. The antimicrobial spectrum of dirithromycin is similar to that of erythromycin; both antibiotics are active against gram-positive bacteria, Legionella spp., Helicobacter pylori, and Chlamydia trachomatis. Comparable results were obtained for each antibiotic in MIC and MBC determinations and in the potential development of resistance in vitro. The effects of human serum, bacterial growth media, test methodology, and inoculum size on MICs were similar for each antibiotic. In standard mouse protection studies, dirithromycin was more efficacious than erythromycin against experimental infections after subcutaneous administration of antibiotic. These results were consistent with pharmacokinetic studies in rodents, which showed that dirithromycin gave more persistent concentrations of antibiotic in serum and tissues than were achieved with erythromycin. These studies indicate that dirithromycin possesses antimicrobial activity comparable to that of erythromycin in vitro but is more active than erythromycin in vivo, which may be attributable to the persistence of antimicrobial activity in the tissue(s) of the test animals.
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PMID:Synthesis and antimicrobial evaluation of dirithromycin (AS-E 136; LY237216), a new macrolide antibiotic derived from erythromycin. 192 52

Dirithromycin is a semisynthetic derivative of erythromycin, a 14-membered ring macrolide antibiotic. The drug is converted during absorption and distribution, to an active metabolite 9-(S)-erythromycylamine, which is the predominant compound found in plasma and extravascular tissues. High tissue concentration of erythromycylamine is achieved after oral doses of dirithromycin, with slow release back into the circulation. The mechanism of action of dirithromycin is like that of erythromycin and other macrolides. These compounds inhibit RNA-dependent protein synthesis. It has recently been suggested that all macrolides stimulate dissociation of peptidyl-tRNA from ribosomes during the elongation phase, leading to inhibited protein synthesis. The antimicrobial spectrum of dirithromycin is similar to that of erythromycin, although the drug offers no significant advantage with regard to MIC values. In vitro against Gram-positive isolates, dirithromycin exhibits similar potency to that of clarithromycin, erythromycin, roxithromycin, and clindamycin. In vivo, dirithromycin is active against penicillin-susceptible Staphylococcus aureus, beta-hemolytic streptococci, and Streptococcus pneumoniae. Dirithromycin is as effective as penicillin VK against streptococcal pharyngitis and tonsilitis, and as effective as erythromycin against acute superimposed chronic bronchitis and skin and soft-tissue infections. In comparison with other newer macrolides, dirithromycin has shown similar or lesser in vitro activity. In particular, Haemophilus influenzae, Bacteroides spp., Peptococcus-Peptostreprococcus spp., Clostridium perfringens, Legionella spp., Neisseria gonorrhoeae, and Chlamydia trachomatis were all less sensitive to dirithromycin than azithromycin or clarithromycin. Once-daily oral administration of dirithromycin (500 mg) has been demonstrated to be similar in efficacy to erythromycin (250 mg, 4 times daily), each for approximately 7 days, in the treatment of acute bronchitis or acute-exacerbations of chronic bronchitis in controlled studies. Proven or presumed pathogen eradication rates were 83 and 86% for acute bronchitis patients treated with dirithromycin and erythromycin, respectively. Corresponding bacteriological response rates in acute exacerbations of chronic bronchitis were 75 to 84% with dirithromycin and 75 to 82% with erythromycin. Both agents achieved clinical cure or improvement in over 85% of the patients with either condition. The main advantage of dirithromycin over erythromycin appears to be once-daily administration. Lilly launched dirithromycin in September 1993, in Spain, received approval from FDA in August 1995, and launched it during October 1995.
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PMID:New drugs--reports of new drugs recently approved by the FDA. Dirithromycin. 873 38

The use of macrolides for treatment of respiratory complaints has been complicated by susceptibility test conditions that adversely effect the in vitro test results and perceived potencies of these compounds. Dirithromycin was studied as to its in vitro activity compared to other macrolides as well as the effects that environmental incubation variations and inoculum concentrations may have on susceptibility results. Dirithromycin was less active than other macrolides tested (azithromycin clarithromycin, erythromycin) against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis with MIC90 values of 16, 32, and 1 microgram/ml, respectively; an activity that was most similar to roxithromycin. This reduced activity may be compensated by the superior pharmacokinetic properties that dirithromycin possesses compared to other members in its class. Method variation studies show that incubation in CO2 environments increase the MIC values for all macrolide compounds and dirithromycin was most effected by pH changes in three in vitro methods tested (Etest [AB BIODISK, Solna, Sweden] broth microdilution, and disk diffusion). Variations in inoculum concentration had minimal effect on dirithromycin potency. In addition the variability (lack of reproducibility) of the test results with dirithromycin were not significant. Dirithromycin is an alternative therapeutic choice among macrolide compounds for treatment of community-acquired respiratory infections caused by various streptococci, Legionella pneumophilia, Mycoplasma pneumoniae and M. catarrhalis, and also possesses a modest in vitro potency versus H. influenzae coupled with excellent pharmacokinetic properties. In vitro tests with dirithromycin will continue to be problematic for H. influenzae because of the adverse effects of recommended CO2 incubation for some standardized methods or commercial products (Etest).
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PMID:Comparative in vitro evaluation of dirithromycin tested against recent clinical isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, including effects of medium supplements and test conditions on MIC results. 1021 55