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BC-3781 is a novel semisynthetic pleuromutilin antibiotic inhibiting bacterial protein synthesis. BC-3781 has completed a phase 2 clinical trial in acute bacterial skin and skin structure infections (ABSSSI). Its antibacterial spectrum additionally covers the predominant pathogens causing community-acquired bacterial pneumonia (CABP). In this study, the antibacterial activity of BC-3781 was evaluated against a contemporary collection of 10,035 bacterial isolates predominately causing ABSSSI and CABP, among other infections, collected within the SENTRY Antimicrobial Surveillance Program worldwide in 2010. BC-3781 exhibited potent activity against organisms commonly isolated from ABSSSI such as Staphylococcus aureus (MIC50/90, 0.12/0.12 μg/ml; 99.8% inhibited at ≤0.5 μg/ml), beta-hemolytic streptococci (MIC50/90, 0.03/0.03 μg/ml; 99.3% inhibited at ≤0.5 μg/ml), and coagulase-negative staphylococci (CoNS; MIC50/90, 0.06/0.12 μg/ml; 97.8% inhibited at ≤1 μg/ml). BC-3781 displayed similar MIC distributions among methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) S. aureus strains. BC-3781 was also active against Enterococcus faecium, with 76.3% of vancomycin-susceptible and 97.0% of vancomycin-resistant isolates being inhibited at BC-3781 concentrations of ≤1 μg/ml. Beta-hemolytic and viridans group streptococci were highly susceptible to BC-3781, with 99.3% and 96.7% of isolates inhibited at ≤0.5 μg/ml, respectively. Further, activity of BC-3781 against Streptococcus pneumoniae (MIC50/90, 0.12/0.25 μg/ml), Haemophilus influenzae (MIC50/90, 1/2 μg/ml), and Moraxella catarrhalis (MIC50/90, 0.12/0.25 μg/ml) was not negatively influenced by β-lactamase production or resistance to other antimicrobial classes tested. In all, BC-3781 displayed a very potent antibacterial profile including the most prevalent bacterial pathogens causing ABSSSI and CABP, thus warranting further clinical development of this antibiotic in these and possibly other indications.

antimicrobial agents and chemotherapy

Antimicrobial Activity of the Pleuromutilin Antibiotic BC-3781 against Bacterial Pathogens Isolated in the SENTRY Antimicrobial Surveillance Program in 2010