F1-3999 48th Interscience Conference on Antimicrobial Agents and Chemotherapy October 25-28, 2008. Washington, DC The Activity of RTA-3, a Novel Antimicrobial Peptide, Against Staphylococcus aureus (SA) of Various Resistance Phenotypes M. Wootton1, T. Caetano3, C. Dempsey4, A. Hawrani4, T. R. Walsh2 and R. A Howe1 1NPHS Microbiology, University Hospital Wales, Cardiff, UK. 2Cardiff University, Cardiff, UK. 3Departamento de Biologia, Universidade de Aveiro, Portugal; 4Bristol University, Bristol, UK Introduction Materials and Methods Results Table 2: MIC range, MIC50 and MIC90 for RTA-3 against MSSA, MRSA, hGISA and GISA Staphylococcus aureus (SA) infections cause serious disease in the community and hospitals world-wide. The establishment and emergence of resistance phenotypes to meticillin (M) and glycopeptides, including vancomycin and teicoplanin makes demands upon treatment options and the health budget. RTA-3 is a 16 amino acid antimicrobial peptide derived from a peptide produced by Streptococcus mitis. It has been developed to optimise activity against multiply resistant Gram negatives including Pseudomonas aeruginosa, Acinetbacter spp., and Stenotrophomonas maltophilia. The current study assesses the activity of RTA-3 against SA with different susceptibilities to M or vancomycin (V) using modified in-vitro testing. 48 SA strains were tested (Table 1): 12 M sensitive, V sensitive (MSSA), 12 M resistant/V sensitive (MRSA), 12 hetero-V intermediate resistant (hGISA), 12 V intermediate (GISA) from an international collection. Susceptibility was determined by microbroth and agar dilution using CLSI standards, Mueller-Hinton media was solidified with agarose. Minimum inhibitory concentrations (MIC) were calculated and compared. The MICs were comparable between microbroth and agar dilution, suggesting the agarose modification for agar dilution was acceptable. Table 2 shows susceptibilities to RTA-3 (mg/L) plus MIC50 and MIC90s for the 48 strains tested. MSSA strains appeared the most susceptible. Glycopeptide sensitive and intermediate phenotypes exhibited similar MICs . Conclusions Table 1: Phenotypic characteristics of strains used MICs were generally between 8 – 64mg/L, with GISA and MSSA showing the most susceptibility. These results are encouraging for the further modification of the peptide to optimise activity against S. aureus. The finding of activity against Gram positive organisms supports the hypothesis that RTA-3 has an extra site of action in addition to the Gram negative outer membrane. Figure: RTA-3 binding to negatively charged membranes Contact details: Tel:+44 2920 746581 Fax:+44 2920 744130 Email: mandy.wootton@nphs.wales.nhs.uk