In vitro antibacterial activity of the peptide deformylase inhibitor BB-83698

Abstract

Objectives: BB-83698 is a peptide deformylase inhibitor currently in clinical trials in Europe. The purpose of this study was to provide additional susceptibility data from clinical isolates, including drug-resistant strains.

Methods: The in vitro activities of BB-83698 and comparators were determined against 281 streptococci, 154 Staphylococcus aureus, 110 Haemophilus influenzae and 50 Moraxella catarrhalis strains selected for their resistance phenotypes. Broth microdilution MICs and MBCs were determined according to NCCLS guidelines.

Results: The MIC90s were 0.25-0.5 mg/L for S. pneumoniae, including penicillin-, erythromycin-, levofloxacin- and multidrug-resistant strains. The MIC90s for Streptococcus pyogenes and Streptococcus agalactiae were 0.12 mg/L and for viridans streptococci, the MIC90 was 0.5 mg/L. Against S. aureus, including oxacillin- and levofloxacin-resistant strains, and vancomycin-intermediate strains, the MIC90 was 8 mg/L. Against beta-lactamase-negative and -positive H. influenzae, the MIC90s were 32 and 64 mg/L, respectively, and against both beta-lactamase-negative and -positive M. catarrhalis the MIC90 was 0.12 mg/L. In MBC studies, the ratio of MBC/MIC was 1:1 or 2:1 against 31% of S. pneumoniae, 33% of S. aureus, 63% of H. influenzae and 9% of M. catarrhalis.

Conclusions: Although BB-83698 has reduced in vitro activity against H. influenzae, it is a potent antimicrobial with excellent activity against streptococci and Moraxella.