title: Comparative in vitro activities of SMT19969, a new antimicrobial agent, against Clostridium difficile and 350 gram-positive and gram-negative aerobic and anaerobic intestinal flora isolates.
abstract: The comparative in vitro activity of SMT19969, a novel, narrow-spectrum, nonabsorbable agent, was studied against 50 ribotype-defined Clostridium difficile strains, 174 Gram-positive and 136 Gram-negative intestinal anaerobes, and 40 Gram-positive aerobes. SMT19969 was one dilution more active against C. difficile isolates (MIC range, 0.125 to 0.5 μg/ml; MIC90, 0.25 μg/ml), including ribotype 027 strains, than fidaxomicin (range, 0.06 to 1 μg/ml; MIC90, 0.5 μg/ml) and two to six dilutions lower than either vancomycin or metronidazole. SMT19969 and fidaxomicin were generally less active against Gram-negative anaerobes, especially the Bacteroides fragilis group species, than vancomycin and metronidazole, suggesting that SMT19969 has a lesser impact on the normal intestinal microbiota that maintain colonization resistance. SMT19969 showed limited activity against other Gram-positive anaerobes, including Bifidobacteria species, Eggerthella lenta, Finegoldia magna, and Peptostreptococcus anaerobius, with MIC90s of >512, >512, 64, and 64 μg/ml, respectively. Clostridium species showed various levels of susceptibility, with C. innocuum being susceptible (MIC90, 1 μg/ml) and C. ramosum and C. perfringens being nonsusceptible (MIC90, >512 μg/ml). Activity against Lactobacillus spp. (range, 0.06 to >512 μg/ml; MIC90, >512 μg/ml) was comparable to that of fidaxomicin and varied by species and strain. Gram-positive aerobic cocci (Staphylococcus aureus, Enterococcus faecalis, E. faecium, and streptococci) showed high SMT19969 MIC90 values (128 to >512 μg/ml).
authors.affiliation: R. M. Alden Research Laboratory, Culver City, California, USA.
authors.forename: Ellie J C
authors.initials: EJ
authors.lastname: Goldstein
authors.forename: Diane M
authors.initials: DM
authors.lastname: Citron
authors.forename: Kerin L
authors.initials: KL
authors.lastname: Tyrrell
authors.forename: C Vreni
authors.initials: CV
authors.lastname: Merriam
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001407:Bacillus / Q000187:drug effects; D001420:Bacteria, Aerobic / Q000187:drug effects*; D001421:Bacteria, Anaerobic / Q000187:drug effects*; D001644:Bifidobacterium / Q000187:drug effects; D016360:Clostridioides difficile / Q000187:drug effects*; D013293:Enterococcus faecalis / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D007422:Intestines / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D010462:Peptostreptococcus / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents