The in vitro activity of a new crystalline derivative of thienamycin, N-formimidoyl thienamycin (MK0787), was tested against 46 laboratory reference strains and 2,158 clinical isolates of gram-positive and -negative bacteria, including anaerobes, and compared with cefoxitin, cefazolin, carbenicillin, and amikacin. MK0787 was significantly more active than the reference antibiotics against most bacteria tested. MK0787 was 16-to 500-fold more active than the other antibiotics against Staphylococcus aureus, Streptococcus pneumoniae, and group A and group B streptococci, inhibiting most isolates at concentrations less than 0.031 ,ug/ml. The inhibition concentration against over 90% of 156 strains of Streptococcus faecalis was 1 yg/ml. MK0787 had slightly less activity than carbenicillin against Haemophilus influenzae. The minimal inhibitory concentrations of MK0787 against strains of Enterobacter spp., Citrobacter spp., Serratia marcescens, Pseudomonas aeruginosa, and Clostridium difficile that are resistant to currently available antibiotics were less than or equal to 4 ,ug/ml. The only species found resistant to MK0787 was Pseudomonas maltophilia, which was equally nonsusceptible to the other reference antibiotics.N-Formimidoyl thienamycin (MK0787) The strains of Neisseria gonorrhoeae were grown on chocolate agar plates, and colonies were suspended in Trypto-soy broth just before dilution.Mueller-Hinton agar (BBL Microbiology Systems) was used for susceptibility determinations unless otherwise specified. This medium supplemented with 5% sheep blood and Brucella agar (BBL Microbiology Systems) supplemented with 5% sheep blood and 10 ug of hemin per ml were used for determining the susceptibilities of streptococci and anaerobes, respectively. Chocolate Mueller-Hinton agar was used for H. influenzae and N. gonorrhoeae. An inoculum prepared by dilution of a fresh overnight broth culture was placed on susceptibility testing plates with a 27-prong metal replicater (Microplanter, Sakuma Seisakusho, Ltd.) of which each inoculation prong was 912 on May 11, 2018 by guest http://aac.asm.org/ Downloaded from
The susceptibilities of 462 clinical anaerobic bacterial isolates to N-formimidoyl thienamycin and 16 other currently available and investigational antibiotics were determined by the agar dilution technique. N-Formimidoyl thienamycin was significantly more active than the reference antibiotics against most organisms tested, especially Bacteroides sp., including clindamycin-resistant strains. All 462 isolates were inhibited by 4 pLg of N-formimidoyl thienamycin per ml, and no resistant strains were found in the species tested. N-Formimidoyl thienamycin was less active (i.e., had a higher 50o minimal inhibitory concentration) against Fusobacterium sp. than clindailycin, SM-1652, and
CM-55 is a synthetic analogue of the antibiotic cerulenin with the chemical structure of 2, 3-dodecenyl-4-oxo-dimethyl amide. This compound inhibited the growth of
Saccharomyces cerevisiae
ATCC 12341 and inhibited protein and lipid synthesis by 91 and 95%, respectively, at a concentration of 50 μg/ml (2.1 × 10
−4
M). The inhibition of protein synthesis was associated with the partial reduction of ribonucleic acid synthesis and leucine transport. The mechanism of inhibition of lipid synthesis was further investigated in a cell-free extract of the yeast. CM-55 inhibited the incorporation of [
14
C]acetyl Coenzyme A (CoA) into both fatty acid (FAF) and non-saponifiable fractions (NSF). However, it did not inhibit [
14
C]malonyl CoA incorporation into FAF and only slightly inhibited [
14
C]mevalonate incorporation into NSF. The activity of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) synthase was inhibited more strongly than the incorporation of [
14
C]3-hydroxy-3-methylglutaryl CoA into NSF; this could account for the CM-55 inhibition of [
14
C]acetyl CoA incorporation into NSF.
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