Antimicrobial activity and spectrum of the new glycylcycline, GAR-936 tested against 1,203 recent clinical bacterial isolates

The in vitro activity of GAR-936, a new semisynthetic glycylcycline, was evaluated in comparison with two tetracyclines and several other antimicrobial agents. A total of 1, 203 recent clinical isolates were tested by reference broth or agar dilution methods. Among the members of the family Enterobacteriaceae, GAR-936 was generally two- to four-fold more active than minocycline, and two- to 16-fold more active than tetracycline. All enteric bacilli MIC90 results were less than or equal to 4 mu g/mL; the exception being Proteus mirabilis and indole-positive Proteae (greater than or equal to 8 mu g/mL). GAR-936 demonstrated excellent activity against all Gram-positive cocci with 90% of the penicillin-resistant Streptococcus pneumoniae isolates inhibited at 0.03 mu g/ml, while the same isolates had a MIC90 of 8 and > 8 mu g/mL for minocycline and tetracycline, respectively. All Enterococcus spp., including vancomycin-resistant isolates, were inhibited at 0.25 mu g/mL of GAR-936 (MIC90, 0.12 or 0.25 mu g/mL). Although GAR-936 (MIC50, 0.25 mu g/mL) was two-fold less active than minocycline (MIC50, 0.12 mu g/mL) against oxacillin-resistant Staphylococcus aureus, all isolates were inhibited at less than or equal to 0.25 mu g/mL. GAR-936 demonstrated good activity against nonfermentative bacteria such as Acinetobacter spp. (MIC90, mu g/ml) and Stenotrophomonas maltophilia (MIC90, 4 mu g/mL), but the compound exhibited only modest activity against Pseudomonas aeruginosa (MIC50, 8 mu g/mL). Haemophilus influenzae (MIC90, 1-2 mu g/mL), Moraxella catarrhalis (MIC90, 0.12 mu g/mL), and various Neisseria spp. (MIC90, 0.12-0.5 mu g/mL) were susceptible to GAR-936. These results indicate that GAR-936 has potent in vitro activity against a wide range of clinically important pathogenic bacteria, and that several Gram-positive and -negative isolates resistant to older tetracyclines and other drug classes remain susceptible to GAR-936, the newest glycylcycline candidate for clinical use. (C) 2000 Elsevier Science Inc. All rights reserved.