Antibacterial activity of tigemonam dicholate (SQ 30836) and interaction with beta-lactamases of gram-negative bacteria. 1989

A Raimondi, and C E Cocuzza
Institute of Medical Microbiology, University of Milan, Italy.

SQ 30836 is an orally absorbed salt of tigemonam, a new monobactam similar to aztreonam in structure and microbiologic properties. When assayed against 400 clinical isolates, tigemonam's activity was similar to that of aztreonam and carumonam. It was highly effective against Enterobacteriaceae but showed poor activity against gram-positive organisms. It inhibited 90% of Escherichia coli, Klebsiella, Shigella, Yersinia, Proteus, Providencia, and Morganella strains at 0.5 micrograms/mL or less, and all Salmonella and Hafnia strains at 1 micrograms/mL or less. Citrobacter, Enterobacter, and Serratia strains were less susceptible (minimum inhibitory concentrations [MIC30] of 2, 32, and 8 micrograms/mL respectively). The activity of the new compound against Enterobacteriaceae is comparable with and often higher than that of third-generation cephalosporins and oral comparison compounds. In contrast to aztreonam, tigemonam had minimal activity against Pseudomonas sp and glucose nonfermenting gram-negative bacteria. Data suggest that poor penetration through the outer membranes of Pseudomonas sp may be responsible for this failure. Tigemonam was stable to hydrolysis by plasmid-mediated and chromosomal beta-lactamases. It was more stable than aztreonam to hydrolysis by the Kl enzyme of Klebsiella and by the Proteus vulgaris beta-lactamase. Also, measurement of the IC50 (concentration of inhibitor able to reduce the activity of the enzyme by 59%) showed that tigemonam has less affinity than aztreonam for class I cephalosporinases. However, only levels of beta-lactamase, not hydrolysis rates or affinity, correlated to MICs of the two monobactams for the resistant Enterobacter and Citrobacter strains.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D008997 Monobactams Monocyclic, bacterially produced or semisynthetic beta-lactam antibiotics. They lack the double ring construction of the traditional beta-lactam antibiotics and can be easily synthesized. Antibiotics, Monobactam,Monobactam,Monocyclic beta-Lactam,Monocyclic beta-Lactams,beta-Lactams, Monocyclic,Monobactam Antibiotics,Monocyclic beta Lactam,Monocyclic beta Lactams,beta Lactams, Monocyclic,beta-Lactam, Monocyclic
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D006090 Gram-Negative Bacteria Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. Gram Negative Bacteria
D006868 Hydrolysis The process of cleaving a chemical compound by the addition of a molecule of water.
D001618 beta-Lactamases Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. beta-Lactamase,beta Lactamase,beta Lactamases

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