Reaction of roxithromycin and clarithromycin with macrolide-inactivating enzymes from highly erythromycin-resistant Escherichia coli

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.