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MDL 62208, MDL 62211, and MDL 62873 are three semisynthetic amide derivatives of teicoplanin (MDL 62208 is an amide of teicoplanin aglycone, MDL 62211 is an amide of the teicoplanin A2 complex, and MDL 62873 is the corresponding derivative of peak A2-2 of the complex). The three semisynthetic glycopeptides were evaluated for in vitro antibacterial activity in comparison with the parent drug (teicoplanin) and vancomycin. A variety of gram-positive bacteria of clinical origin, whose species were carefully determined and that included 428 staphylococci (207 methicillin susceptible and 221 methicillin resistant), 41 streptococci, 82 enterococci, 43 strains of Listeria monocytogenes, 10 JK coryneform bacteria, and 67 anaerobes belonging to the genera Clostridium, Propionibacterium, Peptostreptococcus, and Eubacterium, were tested. The only resistances to MDL 62208, MDL 62211, and MDL 62873 were encountered with vancomycin- and teicoplanin-resistant enterococci. All of the other test strains, including some teicoplanin-resistant coagulase-negative staphylococci of the species Staphylococcus haemolyticus and Staphylococcus epidermidis, were highly susceptible to the three teicoplanin amides. Only minor differences in activity were observed among MDL 62208, MDL 62211, and MDL 62873, whereas the three experimental compounds were usually found to be more potent than teicoplanin or vancomycin (especially against staphylococci, with differences mostly ranging from 2- to 16-fold). The MBC-to-MIC ratios varied depending on the organisms, with the highest ratios usually observed for enterococci and listeriae. Overall, the MBC-to-MIC ratios yielded by the teicoplanin analogs were slightly greater than those yielded by teicoplanin or vancomycin.

In vitro activities of three semisynthetic amide derivatives of teicoplanin, MDL 62208, MDL 62211, and MDL 62873