Abstract
Doripenem is a new 1-β-methyl carbapenem with broad-spectrum activity against clinically important pathogens. Its activity matches imipenem or ertapenem againstGram-positive bacteria and meropenem against Gram-negative bacteria. It may offerslightly more activity than meropenem against selected pathogens. It does not requirethe addition of cilastatin. Doripenem is stable to hydrolysis by most of the β-lacta-mases, excluding carbapenem-hydrolyzing β-lactamases. We performed dockings ofimipenem, meropenem, ertapenem and doripenem with imipenem-hydrolyzing β-lacta-mase, Sme1, separately. Energy calculations revealed that the complex involving doripenem was much less stable. Hence doripenem resists attack by carbapenem-hy-drolyzing β-lactamases at least to some extent. Empiric therapy with doripenem may be useful in hospital settings where multidrug resistance has emerged. However, the proper place for this drug in current antibiotic prescribing practices needs to be determined.