In Vitro Activities of Three New Dihydrofolate Reductase Inhibitors against Clinical Isolates of Gram-Positive Bacteria

摘要

BAL0030543, BAL0030544, and BAL0030545 are dihydrophthalazine inhibitors with in vitro potency against gram-positive pathogens. The MIC50s for methicillin (meticillin)-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, hetero-vancomycin-resistant Staphylococcus aureus, and vancomycin-resistant Staphylococcus aureus (VISA) range from 0.015 to 0.25 μg/ml (MIC90s ≤ 0.5 μg/ml). MIC50s for beta-hemolytic streptococci range from 0.03 to 0.06 μg/ml, MIC50s for Streptococcus pneumoniae range from 0.06 to 0.12 μg/ml, MIC50s for Listeria monocytogenes range from 0.015 to 0.06 μg/ml, and MIC50s for Streptococcus mitis are ≤0.015 μg/ml. These three dihydrophthalazine antifolates have improved potency compared to that of trimethoprim and activity against gram-positive pathogens resistant to other drug classes.(This work was presented in part at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 2008 [].)