Abstract
Clarithromycin, the 6-O-methyl derivative of erythromycin, is approved for treatment of Mycobacterium avium infections and for prophylaxis in patients at risk. Since clarithromycin is more active against mycobacteria than the parent compound, erythromycin, we evaluated the interaction of erythromycin and clarithromycin with cells and ribosomes isolated from M. avium and Mycobacterium smegmatis. The MIC of clarithromycin was 32 and 64 times lower than that of erythromycin for M. smegmatis and M. avium, respectively. The cellular uptake rate for clarithromycin was two- to five-fold faster than for erythromycin, and cell-associated clarithromycin reached a plateau two-fold higher than that of erythromycin after 3 h. Energy was not required for uptake. Fractionation of cell-associated clarithromycin yielded 12% in the walls, 21% bound to ribosomes, with the remainder being lost during work-up. In addition, three- to six-fold more clarithromycin was associated with the isolated cell integument compared with erythromycin. The Kd for clarithromycin binding to ribosomes was 2.9- and 3.5-fold tighter for M. smegmatis and M. avium, respectively, than for erythromycin, due mainly to a slower off-rate. The log partition coefficients of the...Continue Reading
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