Two investigational glycylcyclines, DMG-DMDOT and DMG-MINO antimicrobial activity studied against gram-positive species

DMG-DMDOT (CL-331,002 or CL-331,928) and DMG-MINO (CL-329,998 or CL-344,677) are two new semisynthetic tetracyclines called glycylcyclines, with a broad spectrum of activity that includes Enterobacteriaceae, Gram-positive cocci, JK diphtheroids, and Bacillus cereus. Potent activity was demonstrated against all Streptococcus spp. strains [minimum inhibitory concentrations] (MIC(90)s) 0.06-0.25 mu g/ml) and staphylococci (oxacillin susceptible and resistant; MIC(90)s 0.12-2 mu g/ml). Both glycylcyclines (MIC(90), 0.06 mu g/ml) were more potent than minocycline (MIC(90) 8 mu g/ml) against Enterococcus faecium, many of which were vancomycin resistant (116 strains). Organisms with minocycline MICs at greater than or equal to 8 mu g/ml (Staphylococcus aureus, enterococci, beta-hemolytic streptococci, and pneumococci) had glycylcycline MIC results ranging from 0.06 to 0.5 mu g/ml (e.g., apparent use against existing tetracycline-resistance phenotypes). Drugs in this class appear promising for therapy of infections caused by Gram-positive species now testing resistant to contemporary-antimicrobial agents, and further development of compounds in this class is encouraged.