In-vitro activity of biapenem plus RPX7009, a carbapenem combined with a serine β-lactamase inhibitor against anaerobic bacteria.
Antimicrob Agents Chemother. 2013 Mar 25;
Authors: Goldstein EJ, Citron DM, Tyrrell KL, Merriam CV
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 MIC90 for biapenem-RPX7009 was 1 μg/ml and 4 μg/ml for meropenem. Other B. fragilis group species showed MIC90 of 0.5 μg/ml for both agents. The MIC90s for biapenem-RPX7009 for Prevotella spp. was 0.25 μg/ml, Fusobacterium nucleatum and F. necrophorum 0.125 μg/ml, F. mortiferum 2 μg/ml, F. varium 0.5 μg/ml, Gram-positive cocci and rods ≤0.5 μg/ml, and for clostridia 0.03-8 μg/ml. Against 5 B. fragilis strains harboring a known metallo-beta-lactamase, biapenem-RPX7009 MICs were comparable to those other carbapenems (≥32 μg/ml). Against Bacteroides strains with imipenem MIC of 2 μg/ml, biapenem-RPX7009 had MICs of 0.5-2 μg/ml, and 0.5-32 μg/ml for meropenem, doripenem and ertapenem. For strains with imipenem MICs of 4 μg/ml, the MICs for biapenem-RPX7009 were 4-16 μg/ml and 8->32 μg/ml for meropenem, doripenem, and ertapenem. The inhibitor RPX7009 had no antimicrobial activity when tested alone, and showed little or no potentiation of biapenem vs. anaerobes. Biapenem-RPX7009 showed activity comparable to imipenem and was superior to meropenem, doripenem and ertapenem against imipenem non-susceptible Bacteroides spp.
PMID: 23529731 [PubMed - as supplied by publisher]