title: Antimicrobial activity of the pleuromutilin antibiotic BC-3781 against bacterial pathogens isolated in the SENTRY antimicrobial surveillance program in 2010.
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.
authors.affiliation: Nabriva Therapeutics AG, Vienna, Austria. susanne.paukner@nabriva.com
authors.forename: Susanne
authors.initials: S
authors.lastname: Paukner
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.forename: Zrinka
authors.initials: Z
authors.lastname: Ivezic-Schoenfeld
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology; D004224:Diterpenes / Q000494:pharmacology; D016984:Enterococcus faecium / Q000187:drug effects / Q000254:growth & development; D062665:Epidemiological Monitoring; D006193:Haemophilus influenzae / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects / Q000254:growth & development; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D011083:Polycyclic Compounds; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000254:growth & development; D020713:Vancomycin Resistance / Q000187:drug effects; D000097567:Pleuromutilins
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; D011083:Polycyclic Compounds; D000097567:Pleuromutilins