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

Antimicrob Agents Chemother. 2013 Sep;57(9):4489-95. doi: 10.1128/AAC.00358-13. Epub 2013 Jul 8.

Abstract

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.

Publication types

  • Multicenter Study

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Community-Acquired Infections / drug therapy*
  • Community-Acquired Infections / microbiology
  • Diterpenes / pharmacology
  • Enterococcus faecium / drug effects
  • Enterococcus faecium / growth & development
  • Epidemiological Monitoring
  • Haemophilus influenzae / drug effects
  • Haemophilus influenzae / growth & development
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / growth & development
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification
  • Microbial Sensitivity Tests
  • Moraxella catarrhalis / drug effects
  • Moraxella catarrhalis / growth & development
  • Pneumonia, Bacterial / drug therapy*
  • Pneumonia, Bacterial / microbiology
  • Polycyclic Compounds
  • Staphylococcal Skin Infections / drug therapy*
  • Staphylococcal Skin Infections / microbiology
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / isolation & purification
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / growth & development
  • Vancomycin Resistance / drug effects

Substances

  • Anti-Bacterial Agents
  • Diterpenes
  • Polycyclic Compounds
  • pleuromutilin