In Vitro Evaluation of BI 397, a Novel Glycopeptide Antimicrobial Agent

Abstract

BI 397, a semi-synthetic amide derivative of the experimental glycopeptide, MDL 62,476 (A40926), has excellent In Vitro activity against a wide range of Gram-positive organisms. In this extensive study, 630 contemporary (1998-2000) Gram-positive isolates were selected from various resistance surveillance studies for their resistance patterns to fluoroquinolones, macrolides-lin-cosamides-streptogramins, β-lactams and glycopeptide agents. The BI 397 spectrum of activity was similar to that of other glycopeptides with a MIC₉₀ of <0.5 μg/ml for all tested isolates with the exception of vancomycin-resistant enterococci Van A; (MIC₉₀, 32 μg/ml). BI 397 was more potent than van-comycin and teicoplanin against Staphylococcus aureus (2- to 8-fold), β-haemolytic streptococci (equal to > 16-fold), viridans group streptococci (equal to >32-fold), and Corynebacterium spp. including C. jeikeium (8- to >16-fold). BI 397 was also more active than quinupristin/dalfopristin against all Gram-positive organisms tested with the exception of oxacillin-susceptible S. aureus, against which it had equal activity. BI 397 has little activity against Haemophilus influenzae (MIC₉₀, 64 μg/ml) or other Gram-negative bacilli (MIC₉₀, >64 μg/ml). BI 397 exhibited bacteriostatic activity (like the van-comycin control) versus most species, but was bactericidal against tested Streptococcus pneumoniae. In vitro testing conditions with blood supplemented or free protein containing media elevated BI 397 MIC results, and the 30-mg disk seems acceptable for further disk diffusion test development. Animal pharmacokinetic data published elsewhere suggest that BI 397 may be dosed less frequently than teicoplanin and the results of early studies in humans are awaited with interest, especially when treating teicoplanin-refracto-ry coagulase-negative staphylococci.