1615. In vitro activity of a carbapenem and novel -lactamase (BL) inhibitor (I) combination (RPX2003/RPX7009) tested against contemporary populations of Gram-negative organisms
Session: Poster Abstract Session: Novel Antimicrobial Agents
Saturday, October 20, 2012
Room: SDCC Poster Hall F-H
Background: We evaluated the activity of a carbapenem/serine-BLI (RPX2003/RPX7009 [RPX3/9]) and comparators tested against contemporary Enterobacteriaceae (ENT), P. aeruginosa (PSA) and A. baumannii(ACB).

Methods: 702 ENT, 251 PSA and 154 ACB randomly selected contemporary (2010) clinical isolates collected in a global surveillance program were tested against RPX3/9 (RPX2009 at fixed 4 µg/mL) and comparators using CLSI broth microdilution reference methods. In addition, RPX3/9 was tested against 60 KPC-producing ENT.

Results: Overall, RPX3/9 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) RPX3/9 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 RPX3/9 inhibited 97.4% of isolates at ≤1 µg/mL, whereas IMI and MER inhibited 91.6% at same MIC. RPX3/9 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 RPX3/9 MICs compared to other species (MIC50/90, 1/1, 2/2 and 1/1 µg/mL, respectively). RPX3/9 inhibited all 28 Citrobacter spp. at ≤0.25 µg/mL and the MIC50/90was 0.06/0.12 µg/mL. RPX3/9 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, RPX3/9 exhibited MICs comparable to MER and IMI. Antagonism was not noted in the presence of BLI.

Conclusion: These results demonstrate that the carbapenem/BLI RPX3/9 is a prime candidate for further development that could increase the treatment options against serious infections, including those caused by BL-producing pathogens, such as KPC-producers that are resistant to most β-lactams.

 

Organism (no. tested)

Cumulative % Inhibited at MIC (µg/mL) of RPX3/9 with BLI at 4 µg/mL

≤0.25

0.5

1

2

4

>8

ENT (702)

68.8

78.6

91.7

98.0

100.0

 

KPC-producers (60)

75.0

81.7

93.3

96.7

96.7

100.0

PSA (251)

12.7

48.6

63.4

69.3

71.7

100.0

ACB (154)

33.8

38.3

46.1

48.0

49.4

100.0

Mariana Castanheira, PhD, Miranda Konrardy, Paul Rhomberg and Ronald Jones, MD, JMI Laboratories, Inc., North Liberty, IA

Disclosures:

M. Castanheira, Rempex Pharmaceuticals: Research Contractor, Research support

M. Konrardy, Rempex Pharmaceuticals: Research Contractor, Research support

P. Rhomberg, Rempex Pharmaceuticals: Research Contractor, Research support

R. Jones, Rempex Pharmaceuticals: Research Contractor, Research support

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