title: In vitro activity of Biapenem plus RPX7009, a carbapenem combined with a serine β-lactamase inhibitor, against anaerobic bacteria.
abstract: Biapenem is a carbapenem being developed in combination with RPX7009, a new inhibitor of serine β-lactamases. Biapenem was tested alone and in combination with fixed concentrations of RPX7009 by agar dilution against 377 recent isolates of anaerobes. A separate panel of 27 isolates of Bacteroides spp. with decreased susceptibility or resistance to imipenem was also tested. Comparator drugs included meropenem, piperacillin-tazobactam, ampicillin-sulbactam, cefoxitin, ceftazidime, metronidazole, clindamycin, and tigecycline plus imipenem, doripenem, and ertapenem for the 27 selected strains. For recent consecutive strains of Bacteroides species, the MIC(90) for biapenem-RPX7009 was 1 μg/ml, with a MIC(90) of 4 μg/ml for meropenem. Other Bacteroides fragilis group species showed a MIC90 of 0.5 μg/ml for both agents. The MIC(90)s for biapenem-RPX7009 were 0.25 μg/ml for Prevotella spp., 0.125 μg/ml for Fusobacterium nucleatum and Fusobacterium necrophorum, 2 μg/ml for Fusobacterium mortiferum, 0.5 μg/ml for Fusobacterium varium, ≤ 0.5 μg/ml for Gram-positive cocci and rods, and 0.03 to 8 μg/ml for clostridia. Against 5 B. fragilis strains harboring a known metallo-beta-lactamase, biapenem-RPX7009 MICs were comparable to those of other carbapenems (≥ 32 μg/ml). Against Bacteroides strains with an imipenem MIC of 2 μg/ml, biapenem-RPX7009 had MICs of 0.5 to 2 μg/ml, with MICs of 0.5 to 32 μg/ml for meropenem, doripenem, and ertapenem. For strains with an imipenem MIC of 4 μg/ml, the MICs for biapenem-RPX7009 were 4 to 16 μg/ml, with MICs of 8 to >32 μg/ml for meropenem, doripenem, and ertapenem. The inhibitor RPX7009 had no antimicrobial activity when tested alone, and it showed little or no potentiation of biapenem versus anaerobes. Biapenem-RPX7009 showed activity comparable to that of imipenem and was superior to meropenem, doripenem, and ertapenem against imipenem-nonsusceptible Bacteroides spp.
authors.affiliation: RM Alden Research Laboratory, Culver City, California, USA.
authors.forename: Ellie J C
authors.initials: EJ
authors.lastname: Goldstein
authors.forename: Diane M
authors.initials: DM
authors.lastname: Citron
authors.forename: Kerin L
authors.initials: KL
authors.lastname: Tyrrell
authors.forename: C Vreni
authors.initials: CV
authors.lastname: Merriam
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001421:Bacteria, Anaerobic / Q000145:classification / Q000187:drug effects*; D001441:Bacteroides fragilis / Q000187:drug effects; D015780:Carbapenems / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D018720:Prevotella / Q000187:drug effects; D012694:Serine / Q000378:metabolism; D013845:Thienamycins / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004791:Enzyme Inhibitors; D013845:Thienamycins; D065093:beta-Lactamase Inhibitors; D012694:Serine; D015378:Imipenem; C065257:biapenem