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

Abstract

ABSTRACTBiapenem 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 ofBacteroidesspp. 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 ofBacteroidesspecies, the MIC90for biapenem-RPX7009 was 1 μg/ml, with a MIC90of 4 μg/ml for meropenem. OtherBacteroides fragilisgroup species showed a MIC90of 0.5 μg/ml for both agents. The MIC90s for biapenem-RPX7009 were 0.25 μg/ml forPrevotellaspp., 0.125 μg/ml forFusobacterium nucleatumandFusobacterium necrophorum, 2 μg/ml forFusobacterium mortiferum, 0.5 μg/ml forFusobacterium varium, ≤0.5 μg/ml for Gram-positive cocci and rods, and 0.03 to 8 μg/ml for clostridia. Against 5B. fragilisstrains harboring a known metallo-beta-lactamase, biapenem-RPX7009 MICs were comparable to those of other carbapenems (≥32 μg/ml). AgainstBacteroidesstrains 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-nonsusceptibleBacteroidesspp.