Phosphonomycin is a newly discovered antibiotic produced by streptomycetes. It is effective, when administered by the oral route, to mice infected with Gram-positive or Gram-negative microorganisms. The antibiotic is bactericidal and inhibits cell-wall synthesis.
A new //-lactam antibiotic, named thienamycin, was discovered in culture broths of Streptomyces MA4297. The producing organism, subsequently determined to be a hitherto unrecognized species, is designated Streptomyces cattleya (NRRL 8057). The antibiotic was isolated by adsorption on Dowex 50, passage through Dowex 1, further chromatography on Dowex 50 and Bio-Gel P2, and final purification and desalting on XAD-2. Thienamycin is zwitterionic, has the elemental composition CuHIGN2O4S (M.W.=272.18) and possesses a distinctive UV absorption (Amax=297 nm, e=7,900). Its /3-lactam is unusually sensitive to hydrolysis above pH 8 and to reaction with nucleophiles such as hydroxylamine, cysteine and, to a lesser degree, the primary amine of the antibiotic itself. The latter reaction results in accelerated inactivation at high antibiotic concentrations. * This report was presented in part at the 16th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, Ill., 1976 (q. v. abstract #227) ** This antibiotic is the first representative of a family of des-thia-carbapenem nucleus antibiotics in which the enamine portion of the fused 5-member ring bears a thioethylamine moiety. From this structural feature , the name thienamycin (thi'en-a-mi'san) is derived. THE JOURNAL OF ANTIBIOTICS JAN.
Cefoxitin is a new, cephalosporin-like antibiotic which is highly resistant to hydrolysis by #-lactamase. Ninety-one cultures were selected either for their general resistance to cephalosporin antibiotics or for their ability to produce f-lactamase. Some of these cultures were resistant to cefoxitin. The capacity of each of the 91 strains to hydrolyze cefoxitin with fi-lactamase was determined. Only seven of the cultures degraded the antibiotic as determined by a general assay for fi-lactamase. Several others were able to hydrolyze cefoxitin after enzyme was induced by low concentrations of the antibiotic. The role of the constitutive and inducible enzyme in bacterial resistance to the antibiotic was investigated. Enzymatic destruction of cefoxitin was found to be an important factor contributing to bacterial resistance. However, the complete and rapid degradation of cefoxitin is not essential to resistance since one strain, Enterobacter cloacae 1316, hydrolyzed the antibiotic very slowly but was able to grow unaffected in the presence of cefoxitin. The presence of the enzyme is not necessarily sufficient to confer resistance since another culture, Klebsiella D535, readily hydrolyzed the antibiotic but was susceptible to it. Cefoxitin ( Fig. 1) is a semisynthetic cephamycin analog (12), a new cephalosporin-like antibiotic, with activity against both grampositive and gram-negative bacteria (21). One of its important properties is its uniquely high resistance to hydrolysis by f-lactamase (EC 3.5.2.6 penicillin [cephalosporin] amido-fi-lactam hydrolase). The capacity of a given bacterial strain to produce fi-lactamase is often an important factor in its resistance to the penicillin-and cephalosporin-like antibiotics. The gram-negative bacteria have been shown to produce several fl-lactamases with different substrate profiles (11). We have investigated the resistance of cefoxitin to #B-lactamase hydrolysis in relation to its activity on 91 strains of gram-negative bacteria selected either for their representative resistance pattems to cephalosporin-like antibiotics or for their capacity to produce fi-lactamase. This paper reports the results obtained from such a study. MATERIALS AND METHODSCultures. The cultures used in this study were described by us in a recent publication (3)-. Briefly, 'Present address: Merck Sharp and Dohme, West Point, Pa. 19486. 458 clinical isolates were obtained from five metropolitan hospitals and tested for their in vitro susceptibility to the various cephalosporin antibiotics. Fifty-four cultures were then selected as representative of the cephalosporin-resistant patterns for the various genera included in the original clinical isolates. An additional 38 gram-negative cultures were obtained from M. H. Richmond (Department of Bacteriology, The Medical School, University of Bristol, England), who used these cultures in a study on the classification of #B-lactamases produced by gram-negative bacteria (11).Enterobacter cloacae HSC 18410/62, which produces a potent cephalosporinase con...
A number of actinomycetes isolated from soil were found to produce one or more members of a new family of antibiotics, the cephamycins, which are structurally related to cephalosporin C. The cephamycins were produced in submerged fermentation in a wide variety of media by one or more of eight different species of Streptomyces , including a newly described species, S. lactamdurans . These antibiotics exhibit antibacterial activity against a broad spectrum of bacteria which includes many that are resistant to the cephalosporins and penicillins.
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