AZTHREONAM, A NEW MONOCYCLIC β-LACTAM ANTIBIOTIC; IN VITRO AND IN VIVO ANTIBACTERIAL ACTIVITIES

• Published in: CHEMOTHERAPY Vol. 33; no. Supplement1; pp. 87 - 114
• Main Authors: KITOH, KYOSUKE, KATSU, KANEMASA, SATOH, MASARU, SUGIHARA, YOSHIKI, WATANABE, NAOAKI, TOYOSAWA, TOSHIO, MORIYAMA, MEGUMI
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 25.04.1985
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.33.Supplement1_87

Azthreonam is a novel synthetic monocyclic β-lactam antibiotic. It had excellent activity against gram-negative aerobes including members of the Enterobacteriaceae, Haemophilus influenzae and Pseudomonas aeruginosa, but poor or little activity against anaerobes and gram-positive aerobes. The MIC50 values of Azthreonam against the clinical isolates of Proteus mirabilis and indole-positive Proteus species were 0.005 to 0.015μ/ml, indicating that Azthreonam was 4 to 128-fold more potent than other cephalosporins. It was also highly active against Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens and H. influenzae. The MIC50 values of Azthreonam against those isolates were 0.04, O.03, 0.07, O.12, 0.11, 0.31 and 0.04μ/ml, respectively. Furthermore, Azthreonam was as active as Cefsulodin against P. aeruginosa and was 2 to 3-fold more active than Cefoperazone and Minocycline. Type of or pH of growth medium and the addition of horse serum had no effect on the activity of Azthreonam, but the inoculum size slightly affected its activity as other cephalosporins. Combinations between Azthreonam and other antibiotics showed additive effects from the viewpoint of complementary spectrum and Azthreonam did not interfere with the activities of other antibiotics against gram-positive or anaerobic bacteria. Azthreonam showed an unusually high stability to most of bacterial β-lactamases, but was only slightly hydrolysed by type II penicillinase and β-lactamases produced by K. oxytoca and P. cepacia. The protective effect of Azthreonam against intraperitoneal infection model in mice by P. aeruginosa was superior to Cefoperazone but inferior to Ceftazidime. Azthreonam also exhibited potent activity against urinary tract infection caused by P. mirabilis, respiratory tract infection caused by K. pneumoniae, and inflammatory pouch infection caused by P. aeruginosa. The protective effect of Azthreonam against intraperitoneal infection model in mice by P. aeruginosa was superior to Cefoperazone but inferior to Ceftazidime. Azthreonam also exhibited potent activity against urinary tract infection caused by P. mirabilis, respiratory tract infection caused by K. pneumoniae, and inflammatory pouch infection caused by P. aeruginosa.