In Vitro Activity of a Carbapenem and Novel ß-lactamase Inhibitor Combination (RPX2003/RPX7009) Tested Against Contemporary Populations of Gram-negative Organisms

RESULTS: Overall, BP/RPX9 displayed MIC50/90 of 0.12/1 μg/mL against ENT (Table) compared to an MIC50/90 ≤0.25/>16 μg/mL for FEP and CAZ. Against E. coli (155 strains; MIC50/90 of 0.06/0.06 μg/mL) BP/RPX9 showed greater activity than imipenem (IMI; MIC50/90, 0.12/0.25 μg/mL) and comparable to that of meropenem (MER; MIC50/90, ≤0.015/0.03 μg/mL). Klebsiella spp. (154 strains; 2 species) displayed higher resistance rates compared to other ENT and BP/RPX9 inhibited 97.4% of isolates at ≤1 μg/mL, whereas IMI and MER inhibited 91.6% at same MIC. BP/ RPX9 inhibited 98.3% of 181 Enterobacter spp. at 1 μg/mL and the highest MIC was only 4 μg/mL, ≥four-fold lower than the highest IMI or MER result (16 and >32 μg/mL, respectively). Serratia spp., P. mirabilis and M. morganii displayed slightly higher BP/RPX9 MICs compared to other species (MIC50/90, 1/1, 2/2 and 1/1 μg/mL, respectively). BP/RPX9 inhibited all 28 Citrobacter spp. at ≤0.25 μg/mL and the MIC50/90 was 0.06/0.12 μg/mL. BP/ RPX9 inhibited 93.3% of the KPC-producers at ≤1 μg/mL, compared to only 8.3% for RPX2003 alone at the same MIC. Against PSA and ACB, BP/RPX9 exhibited MICs comparable to MER and IMI. Antagonism was not noted in the presence of BLI.