Comparative Antipneumococcal Activities of Sulopenem and Other Drugs

For 297 penicillin-susceptible, -intermediate, and -resistant pneumococcal strains, the sulopenem MIC50 s were 0.008, 0.06, and 0.25, respectively, and the sulopenem MIC90 s were 0.016, 0.25, and 0.5 μg/ml, respectively. The MIC50 s of amoxicillin for the corresponding strains were 0.03, 0.25, and 2.0 μg/ml, respectively, and the MIC90 s were 0.03, 1.0, and 8.0 μg/ml, respectively. The combination of amoxicillin and clavulanate gave MICs similar to those obtained with amoxicillin alone. The sulopenem MICs were similar to those of imipenem and meropenem. The MICs of ß-lactams increased with those of penicillin G, and among the quinolones tested, moxifloxacin had the lowest MICs. Additionally, 45 strains of drug-resistant type 19A pneumococci were tested by agar dilution and gave sulopenem MIC50 s and MIC90 s of 1.0 and 2.0 μg/ml, respectively. Both sulopenem and amoxicillin (with and without clavulanate) were bactericidal against all 12 strains tested at 2× MIC after 24 h. Thirty-one strains from 10 countries with various penicillin, amoxicillin, and carbapenems MICs, including those with the highest sulopenem MICs, were selected for sequencing analysis of thepbp1a ,pbp2x , andpbp2b regions encoding the transpeptidase active site and MurM. We did not find any correlations between specific penicillin-binding protein-MurM patterns and changes in the MICs.