Disease relevance of AIDS007805

• Comparison of dirithromycin and penicillin for treatment of streptococcal pharyngitis [1].
• Effect of dirithromycin on Haemophilus influenzae infection of the respiratory mucosa [2].
• In vitro activity of dirithromycin against Chlamydia trachomatis [3].
• The presence of dirithromycin slightly increased the intraphagocytic killing of Staphylococcus aureus in human PMNs [4].
• Pharmacokinetics of dirithromycin in patients with mild or moderate cirrhosis [5].

Psychiatry related information on AIDS007805

• Dirithromycin is administered once daily which may contribute to patient compliance [6].

High impact information on AIDS007805

• Therefore, on the limited basis of single-dose administration, no modifications of dirithromycin dosage seem to be required even for patients with class B liver cirrhosis [5].
• The number of bacteria adherent to the mucosa was reduced, although the tissue that had been incubated with dirithromycin (0.125 and 0.5 microg/ml) did not inhibit bacterial growth [2].
• Dirithromycin did not affect the ciliary beat frequency of the nasal epithelium or the transport of mucus on bovine trachea, but dirithromycin (1 microg/ml) did reduce the slowing of the ciliary beat frequency and the damage to the nasal epithelium caused by H. influenzae broth culture filtrate [2].
• By contrast, incubation of adenoid tissue with dirithromycin (0.125 to 1.0 microg/ml) for 4 h prior to assembling the organ culture reduced the mucosal damage caused by subsequent H. influenzae infection by as much as 50% [2].
• Incubation of H. influenzae with dirithromycin at sub-MICs (0.125 and 0.5 microg/ml) prior to infection of the organ cultures did not reduce the mucosal damage caused by bacterial infection [2].

Chemical compound and disease context of AIDS007805

• Being as efficacious as penicillin and having the advantages over erythromycin of once-daily dosing and the lack of drug interactions, dirithromycin is an alternative to penicillin in the treatment of streptococcal pharyngitis for patients 12 years of age and older [1].
• Azithromycin and dirithromycin were the most active compounds against Campylobacter jejuni [7].
• A comparison of 5 days of dirithromycin and 7 days of clarithromycin in acute bacterial exacerbation of chronic bronchitis [8].
• Clinical efficacy of dirithromycin versus miocamycin in the treatment of acute bronchitis or acute exacerbations of chronic bronchitis [9].
• A six-laboratory collaborative study was conducted to develop MIC and zone diameter quality control limits and interpretive criteria for antimicrobial susceptibility testing of Streptococcus pneumoniae with azithromycin, clarithromycin, dirithromycin, and clindamycin [10].

Biological context of AIDS007805

• In a manner similar to that of other highly concentrated, weakly basic antibiotics, dirithromycin inhibited the respiratory burst response (superoxide production) in stimulated PMNs [4].
• In order to determine whether dirithromycin itself possesses significant antimicrobial activity without initial hydrolysis to erythromycylmine, inhibition of cell-free ribosomal protein synthesis was measured under conditions which were adapted to minimize hydrolysis, as measured by analytical HPLC in parallel experiments [11].
• In conclusion, dirithromycin exhibits good tissue distribution within selected tissues, is rapidly distributed and persists in significant concentrations up to 24 h post-dose [12].
• These findings demonstrate that dirithromycin accumulates in human neutrophils, is biologically active intracellularly and modulates leucoattractant-activated superoxide generation and chemotaxis [13].
• Erythromycylamine, the hydrolysis product of dirithromycin, was concentrated significantly less by neutrophils, reaching C/E values of 4 and 19 (at 5 and 120 min) [14].

Anatomical context of AIDS007805

• Interactions of dirithromycin with human polymorphonuclear leukocytes [4].
• The penetration of dirithromycin into bronchoalveolar lavage fluid and alveolar macrophages [15].
• The presence of an inflammatory exudate, especially the phagocytic component, probably contributes to the increased local concentration of dirithromycin found in pathological tissues [12].
• The ability of macrolides to concentrate within phagocytes and alveolar macrophages accounts for the observed high lung tissue concentrations of dirithromycin [12].
• Dirithromycin appears to have adverse effect profiles similar to those of the other macrolides, with reported problems most often related to the gastrointestinal tract [16].

Associations of AIDS007805 with other chemical compounds

• Compared with erythromycin, dirithromycin has a long elimination half-life enabling once-daily administration, and it also achieves a greater cellular:extracellular concentration ratio and higher concentration in some tissues [17].
• Effects of dirithromycin and erythromycylamine on human neutrophil degranulation [18].
• 14- and 15-membered macrolides were active only against S strains; the order of potency in vitro was clarithromycin = erythromycin greater than azithromycin = roxithromycin greater than dirithromycin [19].
• Lack of effect of dirithromycin on theophylline pharmacokinetics in healthy volunteers [20].
• 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) [21].

Gene context of AIDS007805

• This study reports the influence of macrolides, spiramycin and dirithromycin on IL1 beta production [22].
• Cytochrome P-450 complex formation by dirithromycin and other macrolides in rat and human livers [23].
• Dirithromycin may be taken without regard to meals, although food and H2-receptor antagonists may increase the systemic bioavailability in some patients [24].
• CONCLUSIONS: The results of this study suggest comparable clinical efficacy between 5-day courses of once-daily dirithromycin and azithromycin in acute exacerbations of COPD [25].
• None of the parameters for N-desmethylastemizole was different when comparing data by ANOVA from the dirithromycin treatment period with that of the placebo treatment period [26].

Analytical, diagnostic and therapeutic context of AIDS007805

• The pharmacokinetics of dirithromycin were determined over a 72-h period following oral administration of a single 500-mg dose to 8 healthy volunteers and to 16 cirrhotic patients (8 patients with class A cirrhosis and 8 patients with class B cirrhosis according to Pugh's & Child's classification) [5].
• After incubation with radiolabeled dirithromycin, antibiotic uptake by PMNs was determined by a velocity-gradient centrifugation technique and was expressed as the ratio of the cellular to the extracellular drug concentration (C/E) [4].
• A multicentre study comparing the safety and efficacy of dirithromycin with erythromycin in the treatment of bronchitis [27].
• At late post-therapy (three to five weeks after treatment) 82/89 (92.1%) dirithromycin- and 90/93 (96.8%) erythromycin-treated patients had a favourable clinical response [28].
• In a meta-analysis of two identically designed, well-controlled, randomized, double-blind clinical trials, we compared 5 days of dirithromycin with 7 days of erythromycin for acute exacerbations of chronic bronchitis [29].

References