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).
Highlights
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
A new drug, fidaxomicin (4, 5), shows superiority over vancomycin with “sustained cure,” but it does not show improvement in rates of recurrent disease for patients infected with hypervirulent strains (6)
SMT19969 [2,2=bis(4-pyridyl) 3H,3=H 5,5=bibenzimidazole] is a novel, nonabsorbable antibiotic being developed for Clostridium difficile infection (CDI) that had previously been reported to have in vitro activity against C. difficile with a MIC90 of 0.125 g/ml against a panel of 82 United Kingdom clinical isolates (9). It has a very narrow spectrum of activity, with typically Ͼ1,000-fold selectivity for C. difficile over Gram-positive and Gram-negative anaerobic and facultative members of the fecal flora, and it has been successfully tested in both the hamster and human intestinal models of CDI (9, 10, 11). To further evaluate this compound, we studied the comparative in vitro activity of SMT19969 against 50 ribotypedefined clinical strains of C. difficile, 174 Gram-positive and 136 Gram-negative anaerobes, and 40 Gram-positive aerobes
Summary
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. To further evaluate this compound, we studied the comparative in vitro activity of SMT19969 against 50 ribotypedefined clinical strains of C. difficile, 174 Gram-positive and 136 Gram-negative anaerobes, and 40 Gram-positive aerobes. Aerobic organisms Staphylococcus aureus (10) SMT19969 Fidaxomicin Vancomycin Metronidazole
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