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| Arzneimittelforschung, 1977, 27(4), 819 - 23 A new cephalosporin derivative (ST-21) orally administered in laboratory animals; Foresta P et al.; The pivaloxymethyl ester of 7-(D-2-amino-2-phenylacetamido)-desacetoxicephalosporanic acid hydrochloride (ST-21) and cephalexin possess the same bacteridal activity . In fact, in the animal body ST-21 releases cephalexin . The acute toxicity study shows the good tolerance of both substances, whereas the tissue distribution is different, both after oral and i.v . administration . Cephalexin concentrations in some tissues of rats and rabbits, particularly in the lungs and kidneys, are higher and longer-lasting in the animals treated with ST-21 than in those receiving cephalexin, thus showing a different pattern of distribution in the body . For this reason ST-21 might be more suited for the treatment of lung and kidney infections. C R Seances Soc Biol Fil, 1977, 171(5), 1088 - 93 {In vitro effects of aminoglycosides and cephalosporins on rat kidney lysosomes}; Morin JP et al.; The study of aminoglycoside and cephalosporin antibiotics was performed using a subcellular system in vitro . Lysosomes were purified from rat kidney tissue homogenates by a linear sucrose gradient centrifugation technique . The lysosomal membrane integrity was estimated by measuring the free N-acetyl-beta-D-glycosiminidase activity in the incubation medium . A scale of toxicity was established for eleven aminoglycosides and four cephalosporins. J Antibiot (Tokyo), 1976 Dec, 29(12), 1258 - 67 RIT 2214, a new biosynthetic penicillin produced by a mutant of Cephalosporium acremonium; Troonen H et al.; A number of lysine-requiring auxotrophs of Cephalosporium acremonium were investigated for incorporation of side-chain precursors and for accumulation of beta-lactam compounds . One of the auxotrophs, Acremonium chrysogenum ATCC 20389, producing cephalosporin C and penicillin N only if grown in media supplemented with DL-alpha-amino-adipic acid (DL-alpha-AAA), was found to use L-S-carboxymethylcysteine (L-CMC) as a side-chain precursor for the synthesis of a new penicillin (RIT 2214) . No corresponding cephalosporin was detected . The penicillin present in the culture filtrate, was concentrated by adsorption on activated carbon and successive column chromatography on Amberlite IRA-68 and Amberlite XAD-4 . Final purification was achieved by cellulose column chromatography . RIT 2214 was identified as 6-(D)-{(2-amino-2-carboxy)-ethylthio}-acetamido}-penicillanic acid by spectral analysis, bioactivity spectrum, elucidation of side-chain structure and finally by semisynthesis . Its biological properties were also evaluated. Biochim Biophys Acta, 1976 Nov 8, 452(1), 209 - 18 {Nature of the inhibition of some cephalosporinases by carbenicillin}; Labia R et al.; This paper deals with the kinetic inhibition of six cephalosporinases (cephalosporin amido-beta-lactamhydrolase, EC 3.5.2.8) by carbenicillin . In previous cases, the inhibition has appeared usually to be competitive and slowly reversible . This makes it possible to measure the two terms of the ratio Ki=k5/k4;k4 and k5 being respectively the velocity constants of formation and destruction of the enzyme-inhibitor complex . A program was prepared which made it possible to obtain these constants from only one experiment . With ampicillin and cloxacillin, we verified that the reaction is faster, and that only Ki can be measured . These facts suggest that special precautions should be taken in order to obtain signigicant values for the constants governing inhibition. Acta Med Okayama, 1976 Oct, 30(5), 341 - 8 A necropsy case of interstitial nephritis probably related to cefazolin and methenamine; Tanaka T et al.; It is the purpose of this paper to alert the medical community on the potential nephrotoxicity of certain agents among certain patients, especially with some types of renal insufficiency . A young man, who was suffering from apparent renal disturbance, died of massive, post-operative bleeding accompanied by uremia . The uremia occurred within a very rapid clinical course and was related apparently to treatment with methenamine, a ruinary disinfectant, and cefazolin, a cephalosporin derivative . The patient was proved to have a fatal, servere interstitial nephritis based on gross and histological findings of the necropsied kidney, i.e., intense cell infiltration mainly in the interstitum of the cortex, absence of glomerular involvement, and marked softening and enlargement . The present case may suggest how to treat patients suffering from untoward renal ailments with various antibiotics. Scott Med J, 1976 Sep, 20(5), 265 - 8 Cephazolin: clinical studies in obstetrics; Hannay WT et al.; A clinical evaluation of a new cephalosporin, cephazolin, in obstetric patients is presented . Sixteen cardiac patients received the drug prophylactically as antibiotic cover during labour . Eighteen patients with miscellaneous antenatal and puerperal infections received the drug as primary treatment . The data obtained indicate adequate serum and tissue levels with the dose used, and corresponding clinical response . The impression is of a safe and efficaceous drug in the described obstetric situations requiring antibiotic therapy . It may be given prophylactically and with confidence to the cardiac patient in labour. JAMA, 1976 Aug 23, 236(8), 948 - 9 Cephalosporin-associated pseudomembranous colitis; Tures JF et al.; Diarrhea and pseudomembranous colitis appeared in a patient receiving antibiotic therapy with cephalosporin derivatives only . There was a prompt remission following treatment with cholestyramine resin. J Pharm Sci, 1976 Jul, 65(7), 1034 - 8 Ionization constants of cephalosporin zwitterionic compounds; Streng WH et al.; The microionization constants for two zwitterionic compounds were determined by incorporating two experimental techniques . These compounds have chromophoric changes dependent upon the solution pH . By combining the spectrophotometric measurements with potentiometric mmeasurements, all four microionization constants were calculated . The method used is completely general and is applicable to all diprotic compounds that exhibit this spectrophotometric behavior . The observed pKa's had differences of at most 1.2 units for either compound and were in the 1-4 range . A comparison of the results with each compound and similar compounds indicates that the values are resonable. J Pharm Sci, 1976 Jun, 65(6), 887 - 91 Iodmetric and spectrophotometric assays for cephradine after its hydrolysis with a beta-lactamase; Frantz BM; Iodmetric and spectrophotometric methods were developed for the analysis of the new antibiotic cephradine . The procedures are modifications of known methods but are novel in employing a specific beta-lactamase for hydrolysis of the beta-lactam ring of the cephalosporin molecule . The iodometric method is rapid, precise, and accurate, but it requires fairly large amounts of cephradine . The spectrophotometric method, using differential UV absorption at 260 nm, is more rapid and more sensitive than the iodometric method but somewhat less accurate . Both methods proved useful for the routine assay of cephradine in certain formulations. J Bone Joint Surg Am, 1976 Jun, 58(4), 453 - 8 Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: retrospective and prospective analyses; Gustilo RB et al.; In 673 open fractures of long bones (tibia and fibula, femur, radius and ulna, and humerus) treated from 1955 to 1968 at Hennepin County Medical Center, Minneapolis, Minnesota, and analyzed retrospectively, the infection rate was 12 per cent from 1955 to 1960 and 5 per cent from 1961 to 1968 . In a prospective study from 1969 to 1973, 352 patients were managed as follows: debridement and copious irrigation, primary closure for Type I and II fractures and secondary closure for Type III fractures, no primary internal fixation except in the presence of associated vascular injuries, cultures of all wounds, and oxacillin-ampicillin before surgery and for three days postoperatively . In 158 of the patients in the prospective study the initial wound cultures revealed bacterial growth in 70.3 per cent and the infection rate was 2.5 per cent . Sensitivity studies suggested that cephalosporin is currently the prophylactic antibiotic of choice . For the Type III open fractures (severe soft-tissue injury, segmental fracture, or traumatic amputation), the infection rates were 44 per cent in the retrospective study and 9 per cent in the prospective study. J Chromatogr, 1976 May 12, 120(1), 149 - 53 Chromatography of cephalosporins on DEAE-sephadex; Tortolani G et al.; A method is described for separating and quantifying new cephalosporin derivatives by means of column chromatography on DEAE-Sephadex A-25 . The procedure has been used to determine some breakdown products of cefacetril. Antonie Van Leeuwenhoek, 1976, 42(3), 299 - 308 A chemically defined medium for cephalosporin C production by Paecilomyces persicinus; D'Amato RF et al.; A chemically defined medium was developed for the biosynthesis of cephalosporin C by Paecilomyces persicinus Nicot strain P-10 . Glucose served as the major carbon source and nitrogen was supplied by five amino acids, L-arginine, L-aspartic acid, L-glutamic acid, glycine and DL-methionine . Omission of any of the first four diminished or prevented production of cephalosporin C; omission of methionine did not . Methionine is not critical for the production of cephalosporin C in this defined medium . Production of the antibiotic was affected by the concentrations of inorganic salts employed . Biotin was required for growth and cephalosporin C synthesis . The addition of L-lysine precursors to the medium did not influence cephalosporin C levels and L-lysine itself inhibited antibiotic production . Known precursors of beta-lactam antibiotics as well as oleic acid did not affect biosynthesis of cephalosporin C . Chemical changes occurring in the defined medium revealed that glucose was efficiently utilized after 96 hours incubation whereas total soluble nitrogen levels increased following an initial sharp decrease . Mycelial weight and cephalosporin C production were both maximal after 96 hours incubation . Mycelial nitrogen was highest after 48 hours incubation whereas mycelial lipid levels were greatest after 72 hours.
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