Azthreonam (SQ 26,776) is a synthetic monocyclic P-lactam antimicrobial agent belonging to the monobactam family (Sykes et al., Nature [London] 291:489-491, 1981), members of which are characterized by having the 2-oxoazetidine-1-sulfonic acid moiety. Azthreonam exhibits a high degree of stability to Plactamases and is specifically active against aerobic gram-negative bacteria, including Pseudomonas aeruginosa. Its activity against these organisms was in general equal or superior to that observed with the third-generation cephalosporins, cefotaxime and ceftazidime. (Fig. 1). This report summarizes the in vitro and in vivo properties of this novel synthetic antimicrobial agent.MATERIALS AND METHODS Antibiots. Azthreonam was prepared in our own laboratories and used as the disodium salt in all experiments. Cephaloridine was obtained from Eli Lilly & Co., Indianapolis, Ind.; cefoperazone was from Pfizer Inc., New York, N.Y.; cefotaxime was from Hoechst-Roussel; ceftazidime was from Glaxo; cefsulodin was from Abbott Laboratories, North Chicago, Ill.; and cefoxitin was from Merck & Co., Inc., Rahway, N.J.Organsms. The bacterial isolates used were clinical isolates, identified to species by the API system (Analytab Products, Plainview, N.Y.). All isolates were stored in sealed vials in liquid nitrogen. These stock suspensions were used to inoculate plates of brain heart infusion agar which were then incubated for 18 h at 370C. Mueller-Hinton broth (10 ml) was inoculated from these plates to provide log-phase cultures used for minimal inhibitory concentration (MIC) tests.MIC determinations. Antimicrobial activity was determined by an agar dilution method. For nonfastidious organisms the medium employed was antibiotic assay broth (Difco Laboratories, Detroit, Mich.)
In our continued search for the production of j3-lactam-containing molecules from bacteria, we report the isolation and structure determination of a simple carbapenem SQ 27,860, produced by species of Serratia and Erwinia. The antibiotic is highly unstable and isolation was achieved through the p-nitrobenzyl ester.
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