594. In Vitro Potency of Rib-X Novel Compounds against Respiratory Pseudomonas aeruginosa isolates
Session: Poster Abstract Session: Novel Antimicrobial Agents
Friday, October 21, 2011
Room: Poster Hall B1
Background: 

Pseudomonas aeruginosa (PSA) is a common cause of pneumonia in the nosocomial setting carrying with it high morbidity and mortality. Due to increasing resistance, new antimicrobials to treat PSA infections are needed. RX-P766, RX-P770, and RX-P793 are novel compounds that target the large ribosomal subunit of bacteria with activity against PSA. The aim of this study was to compare the in vitro activity of three novel compounds against a host of respiratory isolates.

Methods: 

107 non-duplicate, non-urine, PSA respiratory isolates were selected from 29 United States hospitals over the period of October 2005 to June 2010. MICs were determined by broth microdilution in duplicate for each of the novel compounds and for meropenem, ceftazidime, piperacillin-tazobactam, levofloxacin, and tobramycin. Data were analyzed in aggregate and by patient location (ICU vs non-ICU). Isolates were considered multi-drug resistant (MDR) if resistant to 3 classes of antimicrobials.

Results: 

A total of 59 isolates were collected from the ICU and 48 from ward patients. 27 of the total 107 isolates were MDR with 14 isolates from ICU patients and 13 isolates from ward patients. Mean age ± SD was 53 ± 23 years with nine isolates from patients ≤18 years.  For compounds RX-P766 and RX-P793, over 97% of isolates were inhibited at an MIC of 4 µg/mL while RX-P770 was slightly less potent with >97% inhibition at an MIC of 8 µg/mL. When comparing ICU and non-ICU isolates, all three compounds maintained similar activity. MIC90 for meropenem, ceftazidime, and levofloxacin were 16, ≥128, and 32 µg/mL, respectively for the entire collection and when separated by location.

Conclusion: 

All three novel compounds displayed similar activity against PSA respiratory isolates collected both within, and outside the ICU. RX-P766, RX-P770, and RX-P793 are potent agents with relatively narrow MIC distributions around 2-8 µg/mL, that demonstrated greater in vitro potency than currently utilized antimicrobials for PSA respiratory infections.


Subject Category: A. Antimicrobial agents and Resistance

Seth T. Housman, PharmD, MPA1, Christina Sutherland, BS1 and David Nicolau, PharmD, FCCP, FIDSA2, (1)Ctr. for Anti-Infect R&D, Hartford Hospital, Hartford, CT, (2)Ctr. for Anti-Infect Res. & Dev., Hartford Hospital, Hartford, CT

Disclosures:

S. T. Housman, None

C. Sutherland, None

D. Nicolau, Rib-X Pharmaceuticals: Consultant and Grant Investigator, Consulting fee and Grant recipient

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.