Activity of a novel carbapenem, doripenem, against anaerobic pathogens

Doripenem, a synthetic 1-beta-methyl carbapenem, has a broad-spectrum of activity against almost all species of anaerobic bacteria, including all Bacteroides fragilis group species, most with MIC90 results at <= 1 mu g/mL (with the exception of Sutterella wadsworthensis). Against Clostridium difficile strains, it has a narrow range of inhibitory concentrations (1-4 mu g/mL) that may be achievable in the colon, potentially resulting in lower disease rates. It has been shown to be active in vitro against strains isolated from a variety of clinical infections, including bacteremias, diabetic foot and other soft tissues infections and in intra-abdominal and pelvic sites. In addition, a study of a pyometrium animal model of mixed infections noted a better microbiologic response than with imipenem. Two phase 3 multinational clinical trials of complicated mixed aerobic/anaerobic intra-abdominal infections noted noninferiority of doripenem when compared with meropenem, but in vitro against the anaerobes, it was more potent than meropenem, ertapenem, ... and similar to imipenem. Doripenem activity against anaerobes seems comparable with the other extant carbapenems. Although resistance among anaerobic bacteria to this agent is possible, it remains relatively rare. (C) 2009 Elsevier Inc. All rights reserved.