title: Antimicrobial activity of the novel pleuromutilin antibiotic BC-3781 against organisms responsible for community-acquired respiratory tract infections (CARTIs).
abstract: BACKGROUND
  BC-3781 is an investigational semi-synthetic pleuromutilin antibiotic, which recently finished a clinical Phase 2 trial in acute bacterial skin and skin structure infections. BC-3781 binds to the 50S ribosomal subunit and cross-resistance with other antimicrobial classes is uncommon. We evaluated the activity of BC-3781 against organisms responsible for community-acquired respiratory tract infections (CARTIs).
  
  
  METHODS
  BC-3781 and comparator agents were susceptibility tested against Streptococcus pneumoniae (157 isolates; 33% penicillin resistant), Haemophilus influenzae (102; 50% β-lactamase producers), Moraxella catarrhalis (50) and Legionella pneumophila (30) by broth microdilution and the agar dilution method. Mycoplasma pneumoniae (50 strains) was tested by broth microdilution, while Chlamydophila pneumoniae (50 strains) MIC values were determined using HEp-2 cells.
  
  
  RESULTS
  Against S. pneumoniae (MIC(50/90) 0.12/0.25 mg/L) BC-3781 was 16- and 8-fold more active than azithromycin (MIC(50/90) 2/>16 mg/L) and levofloxacin (MIC(50/90) 1/1 mg/L), respectively, and its activity was not adversely affected by resistance to penicillin. S. pneumoniae showed high resistance rates to azithromycin (50.3%) and clindamycin (31.2%), all being inhibited by BC-3781 at concentrations ≤0.5 mg/L. H. influenzae and M. catarrhalis exhibited low BC-3781 MIC values independent of β-lactamase production. BC-3781 activity against L. pneumophila (MIC(50/90) 0.06/0.5 mg/L) was similar to that of erythromycin, but lower than that of azithromycin. BC-3781 also showed potent activity against M. pneumoniae and C. pneumoniae, with MIC(50/90) of 0.006/0.006 and 0.02/0.04 mg/L, respectively.
  
  
  CONCLUSIONS
  BC-3781 was very active against organisms commonly associated with CARTIs and its activity was not negatively influenced by resistance to other antimicrobials.
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA. helio-sader@jmilabs.com
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.forename: Susanne
authors.initials: S
authors.lastname: Paukner
authors.forename: Zrinka
authors.initials: Z
authors.lastname: Ivezic-Schoenfeld
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Biedenbach
authors.forename: Franz J
authors.initials: FJ
authors.lastname: Schmitz
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D001424:Bacterial Infections / Q000382:microbiology*; D017714:Community-Acquired Infections / Q000382:microbiology*; D004224:Diterpenes / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D011083:Polycyclic Compounds; D012141:Respiratory Tract Infections / Q000382:microbiology*; D000097567:Pleuromutilins
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; D011083:Polycyclic Compounds; D000097567:Pleuromutilins