IN-VITRO ACTIVITIES OF 2 GLYCYLCYCLINES AGAINST GRAM-POSITIVE BACTERIA

The glycylcyclines designated CL 329,998 and CL 331,002 are N,N-dimethylglycylamido derivatives of minocycline and 6-demethyl-6-deoxytetracycline, respectively. In vitro activities of these two antimicrobial agents were compared with those of tetracycline, minocycline, and seven other antimicrobial agents against 412 gram-positive organisms. Both new drugs were significantly more active than minocycline against methicillin-resistant Staphylococcus aureus (MICs for 90% of isolates tested, 0.25 and 0.5 mu g/ml versus 4 mu g/ml). CL 329,998 inhibited all streptococci, lactobacilli, and Leuconostoc spp. at concentrations of less than or equal to 0.5 mu g/ml, with CL 331,002 slightly less active against some species. All enterococci, including minocycline-resistant and multidrug-resistant isolates, were inhibited at less than or equal to 0.5- and less than or equal to 1.0-mu g/ml concentrations of the new drugs, respectively. Only bacteriostatic activity was evident by lime-kill curves. The two glycylcyclines demonstrated activities in vitro that were superior to those of minocycline against several gram-positive bacterial species, and at relatively low concentrations, they inhibited isolates resistant to both tetracycline and minocycline.