Comparative In Vitro Activities of LFF571 against Clostridium difficile and 630 Other Intestinal Strains of Aerobic and Anaerobic Bacteria

The in vitro activities of LFF571, a novel analog of GE2270A that inhibits bacterial growth by binding with high affinity for protein synthesis elongation factor Tu, fidaxomicin, and 10 other antimicrobial agents were determined against 50 strains of Clostridium difficile and 630 other anaerobic and aerobic organisms of intestinal origin. LFF571 possesses potent activity against C. difficile and most other Gram-positive anaerobes (MIC90, ≤0.25 μg/ml), with the exception of bifidobacteria and lactobacilli. The MIC90s for aerobes, including enterococci, Staphylococcus aureus (as well as methicillin-resistant S. aureus [MRSA] isolates), Streptococcus pyogenes, and other streptococci were 0.06, 0.125, 2, and 8 μg/ml, respectively. Comparatively, fidaxomicin showed variable activity against Gram-positive organisms: MIC90s against C. difficile, Clostridium perfringens, and Bifidobacterium spp. were 0.5, ≤0.015, and 0.125 μg/ml, respectively, but >32 μg/ml against Clostridium ramosum and Clostridium innocuum. MIC90 for S. pyogenes and other streptococci was 16 and >32 μg/ml, respectively. LFF571 and fidaxomicin were generally less active against Gram-negative anaerobes.