In Vitro Activity of Biapenem plus RPX7009, a Carbapenem Combined with a Serine β-Lactamase Inhibitor, against Anaerobic Bacteria

Biapenem is a carbapenem being developed in combination with RPX7009, a new inhibitor of serine beta-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 MIC90 for biapenem-RPX7009 was 1 mu g/ml, with a MIC90 of 4 mu g/ml for meropenem. Other Bacteroides fragilis group species showed a MIC90 of 0.5 mu g/ml for both agents. The MIC(90)s for biapenem-RPX7009 were 0.25 mu g/ml for Prevotella spp., 0.125 mu g/ml for Fusobacterium nucleatum and Fusobacterium necrophorum, 2 mu g/ml for Fusobacterium mortiferum, 0.5 mu g/ml for Fusobacterium varium, <= 0.5 mu g/ml for Gram-positive cocci and rods, and 0.03 to 8 mu g/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 mu g/ml). Against Bacteroides strains with an imipenem MIC of 2 mu g/ml, biapenem-RPX7009 had MICs of 0.5 to 2 mu g/ml, with MICs of 0.5 to 32 mu g/ml for meropenem, doripenem, and ertapenem. For strains with an imipenem MIC of 4 mu g/ml, the MICs for biapenem-RPX7009 were 4 to 16 mu g/ml, with MICs of 8 to >= 32 mu g/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.