The activities of two new 14-membered-ring macrolide antibiotics, roxithromycin (RXM) and clarithromycin (CAM), against highly erythromycin (EM)-resistant Escherichia coli strains were evaluated. Pretreatment of macrolide phosphotransferase (MPH) (2') I-producing strains with EM increased the MICs of EM and CAM without any noticeable change in the MIC of RXM. The MPH (2') II-producing strain was more susceptible to CAM, while the EM esterase-producing strains were more susceptible to RXM than EM. Pretreatment of these latter two strains with EM did not alter their susceptibility to either RXM or CAM. In addition, the compounds were assessed as substrates for inactivation by crude enzyme preparations. Of the 14-membered-ring macrolides, RXM was the least favored substrate for MPH (2') I or II. CAM and RXM were substrates for the EM esterase but were the least preferred of the 14-membered-ring macrolides.
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T cell proliferation, cytokine production by T cells stimulated through CD28, CD26, or PMA with or without anti-CD3 Mab, cytokine production by macrophages stimulated with lipopolysaccharide, and transendothelial migration of T cells were analyzed in the presence or absence of various concentrations of RXM. We evaluated the effect of RXM treatment in collagen induced arthritis in mice.
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The triple-double ODPT performed with antibiotics in antibiotic/NSAID hypersensitive patients with the purpose of determining a safe alternative antibiotic could be a safe, cost-effective and time-saving alternative to conventional one day one antibiotic ODPT.
Since patients with cystic fibrosis are often treated with alpha dornase to reduce sputum viscosity, and because of preliminary reports of efficacy of long-term low-dose erythromycin therapy in chronic airway diseases, it is likely that alpha dornase and macrolides might be given together in such patients. A possible interaction between these drugs was therefore investigated. Using hyperchromic effect to quantify alpha dornase activity, a time- and dose-dependent inhibitory effect on human DNA hydrolysis has been observed for erythromycin, roxithromycin and azithromycin. Inhibitory doses 50% for alpha dornase were graphically determined. Azithromycin exhibited the strongest inhibitory effect.
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The main outcome was risk of cardiac death associated with clarithromycin and roxithromycin, compared with penicillin V. Subgroup analyses were conducted according to sex, age, risk score, and concomitant use of drugs that inhibit the cytochrome P450 3A enzyme, which metabolises macrolides.
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The only limited positive impact of antibiotic therapy on early atherosclerosis progression in Cp-positive patients observed in our study may explain the negative results of most antibiotic trials on clinical end points.