GAR-936, a new glycylcycline, had lower MICs (<0.016 to 0.125 g/ml) for 201 penicillin-and tetracyclinesusceptible and -resistant pneumococcal strains than tetracycline (<0.06 to 128 g/ml), minocycline (<0.06 to 16.0 g/ml), or doxycycline (<0.06 to 32.0 g/ml). GAR-936 was also bactericidal against 11 of 12 strains tested at the MIC after 24 h, with significant kill rates at earlier time points.The incidence of pneumococcal resistance to penicillin G and other ß-lactam and non-ß-lactam compounds has increased worldwide at an alarming rate (1, 6, 7). In the United States, a recent survey of 1,476 strains showed that 49.6% were penicillin susceptible, 17.9% were of intermediate resistance (penicillin intermediate), and 32.5% were penicillin resistant. Macrolide MICs rose with those of penicillin G, with an overall macrolide resistance level of 33% (8).Resistance to conventional oral tetracyclines (including minocycline and doxycycline) occurs with increased frequency among penicillin-intermediate and -resistant pneumococci, and genes coding for macrolide and tetracycline resistance are carried on the same transposon (6, 7). GAR-936 is a new broad-spectrum parenteral glycylcycline. Preliminary studies have shown that this drug is active against penicillin-susceptible and -resistant pneumococci (13,15).This study compares the activity of GAR-936 against 201 penicillin-susceptible, -intermediate, or -resistant pneumococcal strains with those of three other tetracyclines, four ß-lactams, clarithromycin, and vancomycin. Additionally, the activities of these compounds against 12 penicillin-susceptible and -resistant strains of pneumococci were determined by the broth MIC and time-kill methods.For determination of MICs by agar dilution, 51 penicillinsusceptible, 72 penicillin-intermediate, and 78 penicillin-resistant strains of pneumococci were utilized. For time-kill studies, four penicillin-susceptible, four penicillin-intermediate, and four penicillin-resistant strains were tested; of these, five were tetracycline susceptible (MIC, Յ2.0 g/ml), 1 was tetracycline intermediate (MIC, 4.0 g/ml), and six were tetracycline resistant (MIC, Ն8.0 g/ml).The agar dilution method used in this study to determine MICs of various antimicrobial agents for 201 pneumococcal strains has been used routinely for many years by our group (6, 7); Mueller-Hinton agar (BBL Microbiology Systems, Cockeysville, Md.) supplemented with 5% sheep blood was employed. Microbroth MIC determinations for 12 strains were performed in accordance with the protocol recommended by the National Committee for Clinical Laboratory Standards (9). Standard quality control strains, including Streptococcus pneumoniae ATCC 49619 (9), were included in each run of agar and broth dilution MIC determinations. All MIC studies were performed in air. All strains, recently isolated from stocks stored at Ϫ70°C and subcultured twice, grew in air and did not require added CO 2 for growth. The susceptibility patterns of these strains are representative of those commonly encountered...