600. In vitro and ex-vivo antimicrobial activity of PMX30063-a novel mimic of host defense proteins (HDP)
Session: Poster Abstract Session: Novel Antimicrobial Agents
Friday, October 21, 2011
Room: Poster Hall B1
Background: PolyMedix has developed small nonpeptidic mimics of the host defense proteins (HDP) as antimicrobial agents. The HDP mimics offer several advantages over conventional antibiotics including rapid bactericidal activity, reduced risk for the development of resistance and ease of synthesis. The lead compound, PMX30063, is being developed for the treatment of acute bacterial skin and skin-structure infections and is currently in phase 2 clinical trial. The full spectrum of activity of PMX30063 against both target and non-target pathogens was evaluated in vitro against a diverse array of recent clinical isolates of Gram-positive and Gram-negative pathogens. In addition, ex vivo studies were performed to determine the antimicrobial activity in serum following PMX-30063 infusion into healthy subjects participating in a Phase 1 study.

Methods: The Minimum Inhibitory Concentrations (MIC), the Serum Inhibitory Titres (SIT) and Serum Bactericidal Titers (SBT) were determined following CLSI guidelines.  The clinical isolates were from the U.S.  and were predominantly of skin and wound origin. The SIT and SBT against 2 strains each of MSSA and MRSA were tested in serum samples from 40 subjects that were collected on the first day of drug administration post infusion and then 8 hours later.

Results: The MIC90 of PMX30063 against staphylococci was 1 µg/mL and maintained a consistent activity profile against both MRSA and MSSA strains. Similar bactericidal activities were detected in human serum following drug infusion into volunteers at the 0.1 - 0.4 mg/kg dose level.  MICs90 against E. faecium, E. faecalis and beta-hemolytic streptococci were in range of 2-8 µg/mL. PMX30063 was less active against certain evaluated Gram-negative isolates (MIC90 from 4 to 64 µg/mL).

Conclusion: Overall, PMX30063 was potent against staphylococci and other gram-positive cocci including beta-hemolytic streptococci and E. faecium.  PMX30063 was comparatively less potent against certain evaluated Gram-negative isolates.  In the ex-vivo studies in serum samples following administration of PMX-30063 bacteriostatic and bactericidal concentrations against MSSA and MRSA strains can be achieved in human subjects at doses as low as 0.1 mg/kg.


Subject Category: A. Antimicrobial agents and Resistance

Bozena Korczak, PhD1, Richard Scott, PhD1, Daniel F. Sahm, Ph.D.2 and Chris Pillar3, (1)PolyMedix, Inc., Radnor, PA, (2)Eurofins Medinet, Chantilly, VA, (3)Eurofins, Global Infectious Disease Services, Chantilly, VA

Disclosures:

B. Korczak, PolyMedix, Inc.: Employee, Salary

R. Scott, PolyMedix, Inc.: Employee, Salary

D. F. Sahm, PolyMedix, Inc.: Eurofins hired to perform research studies, Eurofins paid for research studies performed

C. Pillar, PolyMedix: Eurofins hired to perform reaserch studies, Eurofins paid to perform research studies

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.