Doripenem Versus Bacteria: An Emerging Battleground

Doripenem is a new 1-beta-methyl carbapenem with broad-spectrum activity against clinically important pathogens. Its activity matches imipenem or ertapenem against Gram-positive bacteria and meropenem against Gram-negative bacteria. It may offer slightly more activity than meropenem against selected pathogens. It does not require the addition of cilastatin. Doripenem is stable to hydrolysis by most of the beta-lactamases, excluding carbapenem-hydrolyzing beta-lactamases. We performed dockings of imipenem, meropenem, ertapenem and doripenem with imipenem-hydrolyzing beta-lactamase, Sme1, separately. Energy calculations revealed that the complex involving doripenem was much less stable. Hence doripenem resists attack by carbapenem-hydrolyzing beta-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.