Disease relevance of Thienamycin

• Biosynthesis of the beta-lactam antibiotic, thienamycin, by Streptomyces cattleya [1].
• Thienamycin formamidide monohydrate had the broadest spectrum of activity and was the only antibiotic active against Streptococcus faecalis; the only resistant species were P maltophilia and Pseudomonas cepacia [2].
• Inhibition of transpeptidase activity in Escherichia coli by thienamycin [3].
• N-formimidoyl thienamycin was less active than some of the other agents against Enterobacteriaceae, except for the strains of Serratia and Citrobacter studied [4].
• Susceptibilities of anaerobic bacteria to N-formimidoyl thienamycin (MK0787) and to other antibiotics [5].

High impact information on Thienamycin

• The biosynthetic gene cluster for the beta-lactam carbapenem thienamycin in Streptomyces cattleya [6].
• Imipenem is the first available semisynthetic thienamycin and is administered intravenously in combination with cilastatin, a renal dipeptidase inhibitor that increases urinary excretion of active drug [7].
• Cystathionine gamma-lyase (EC 4.4.1.1) was purified from Streptomyces cattleya, an actinomycete which produces the unusual beta-lactam antibiotic thienamycin [8].
• Imipenem (formerly N-formimidoyl thienamycin) and ceftazidime were investigated for their postantibiotic effect on Pseudomonas aeruginosa [9].
• Chemoprophylaxis of experimental rabbit endocarditis with N-formimidoyl thienamycin [10].

Chemical compound and disease context of Thienamycin

• N-formimidoyl thienamycin (MK-787) is a new beta-lactam with potent activity against both aerobic and anaerobic gram-positive and gram-negative bacteria [11].
• Our data suggest that N-formimidoyl thienamycin may have therapeutic efficacy against respiratory infections with P. aeruginosa equivalent to that of tobramycin [12].
• The order of potency in vivo, 0.03 to 0.06 mg/kg for gram-positive species and 0.65 to 3.8 mg/kg for gram-negative infections including Pseudomonas, exceeded that of thienamycin and was at least 10-fold superior to reference beta-lactam antibiotics including two recently developed agents with antipseudomonal activity, cefotaxime and LY127935 [13].
• The therapeutic efficacies of disodium ticarcillin, tobramycin sulfate, and N-formimidoyl thienamycin (MK0787) were compared in guinea pigs with experimentally induced Pseudomonas aeruginosa pneumonia [12].
• Most strains of Pseudomonas aeruginosa were inhibited by ceftazidime, N-formimidoyl thienamycin, and cefsulodin [14].

Biological context of Thienamycin

• Pharmacokinetics and tolerance of N-formimidoyl thienamycin (MK0787) in humans [15].
• One block, induced by N-formimidoyl thienamycin and methicillin, occurred before the completion of chromosome replication, whereas the other, induced by cefoxitin and cephalothin, took place later in the cycle [16].
• Transformants of S. lividans TK24 were obtained by transforming a recombinant plasmid p6BC12 harboring the thienamycin cyclase gene into it [17].
• Enzyme kinetics were studied with various therapeutic compounds as substrates and lamoxactam, azthreonam, and N-formimidoyl thienamycin as inhibitors [18].

Anatomical context of Thienamycin

• After a single intravenous dose of 25 mg/kg, a peak N-formimidoyl thienamycin concentration in cerebrospinal fluid (CSF) of 2.5 micrograms/ml was attained at 45 min [19].
• N-Formimidoyl thienamycin penetrated uninflamed meninges, and peak concentrations were significantly augmented by coadministration of MK791 [20].
• N-formimidoyl thienamycin initially caused the formation of abnormally shaped cells which developed into spheroplasts [21].
• Phagocytic function and antibody-dependent cellular cytotoxicity of human neutrophils in the presence of N-formimidoyl thienamycin [22].

Associations of Thienamycin with other chemical compounds

• The clinical effectiveness of cefotaxime and thienamycin for therapy of disease due to penicillin-resistant pneumococci needs further evaluation, and of particular interest will be the levels of these drugs which can be achieved in cerebrospinal fluid [23].
• Survival rates were 35% for ticarcillin, 80% for tobramycin, and 75% for N-formimidoyl thienamycin [12].
• Antibiotic antagonism seen with in-vitro static tests of piperacillin and thienamycin did not occur with the kinetic model [24].
• The antimicrobials tested were penicillin G, ampicillin, carbenicillin, ticarcillin, piperacillin, mezlocillin, cephalothin, cefoxitin, cefamandole, latamoxef (moxalactam), cefotaxime, cefoperazone, ceftazidime, ceftriaxone, N-formimidoyl thienamycin, SCH 29482, chloramphenicol and vancomycin [25].
• In vitro studies with imipenem (N-formimidoyl thienamycin or MK0787) were performed with 8481 clinical isolates in three separate medical centers [26].

Gene context of Thienamycin

• Lamoxactam and azthreonam failed to inhibit the TEM-1 enzyme, whereas N-formimidoyl thienamycin was a competitive inhibitor [18].
• Comparative in vitro activity of N-formimidoyl thienamycin against gram-positive and gram-negative aerobic and anaerobic species and its beta-lactamase stability [27].
• Metabolism of thienamycin and related carbapenem antibiotics by the renal dipeptidase, dehydropeptidase [28].
• delta 1-Thienamycin (2), a double-bond isomer of thienamycin, was prepared by isomerizing N-[[(p-nitrobenzyl)oxy]-carbonyl]thienamycin p-nitrobenzyl ester (5b) with DBU in Me2SO followed by hydrogenolysis of the protecting groups [29].
• The antibacterial activity of thienamycin against multiresistant bacteria-comparison with beta-lactamase stable compounds [30].

Analytical, diagnostic and therapeutic context of Thienamycin

• 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 [5].
• High-performance liquid chromatographic (HPLC) methods using ultraviolet (UV) detection have been developed for the assay of the antibiotic imipenem (N-formimidoyl thienamycin) in human plasma and urine [31].
• N-formimidoyl thienamycin is a new semisynthetic beta-lactam antibiotic still awaiting clinical trials [32].
• The transformant No. 12 produced a thienamycin-like substance identified by paper chromatography and HPLC analysis [33].

References