Activity of a novel carbapenem, doripenem, against anaerobic pathogens

Abstract

Doripenem, a synthetic 1-β-methyl carbapenem, has a broad-spectrum of activity against almost all species of anaerobic bacteria, including all Bacteroides fragilis group species, most with MIC 90 results at ≤1 μg/mL (with the exception of Sutterella wadsworthensis). Against Clostridium difficile strains, it has a narrow range of inhibitory concentrations (1–4 μg/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.