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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.)

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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.

RP1, a group of genes specifying resistance to carbenicillin, neomycin, kanamycin, and tetracycline and originating in a strain of Pseudomonas aeruginosa , was freely transmissible between strains of P. aeruginosa, Escherichia coli , and Proteus mirabilis . Acquisition of the multiple drug resistance specified by RP1 by these strains was accompanied by acquisition of an extrachromosomal satellite of covalently closed circular deoxyribonucleic acid of molecular weight about 40 million daltons and of buoyant density 1.719 g/cm 3 (60% guanine plus cytosine).

Cefuroxime is a new broad-spectrum cephalosporin antibiotic with increased stability to f8-lactamases. This stability, although no absolute in all cases, has the effect of widening the antibacterial spectrum of the compound so that many organisms resistant to the established cephalosporins are susceptible to cefuroxime. It is active against gram-positive organisms, including penicillinaseproducing staphylococci, but it is less active against methicillin-resistant strains. In addition to its high activity against non-,8-lactamase-producing gram-negative bacteria, cefuroxime effectively inhibits the growth of many 1B-lactamase-producing strains, including Enterobacter, Klebsiella, and indole-positive Proteus spp. It is highly active against Neisseria gonorrhoeae, Neisseria meningitidis, and also Haemophilus influenzae, including ampicillin-resistant strains. Cefuroxime is rapidly bactericidal and induces the formation and subsequent lysis of filamentous forms over a small concentration range.

An outbreak of R-factor-mediated carbenicillin resistance in Pseudomonas aeruginosa in burned patients in March 1969 was followed by a second outbreak 6 months later. No R-factor-carrying P. aeruginosa strains were detected in the intervening period but R-factor-determined lactamase was commonly encountered, particularly in Klebsiella aerogenes strains. A comparison of the molecular properties of the R factors in pseudomonads from the first and second phases with those in the Klebsiella strains from the intervening period showed them to be very closely related. A single R-factor type therefore may have been maintained in the Burns Unit between the two Pseudomonas outbreaks as a plasmid conferring resistance to ampicillin in K. aerogenes .