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. 1991 Feb;35(2):329–334. doi: 10.1128/aac.35.2.329

In vitro activity of a catechol-substituted cephalosporin, GR69153.

R Wise 1, J M Andrews 1, J P Ashby 1, D Thornber 1
PMCID: PMC245000  PMID: 2024966

Abstract

The in vitro activity of GR69153, a new catechol-substituted cephalosporin, was compared with those of ceftazidime, imipenem, meropenem, and ceftriaxone against 604 recent clinical isolates and other strains with known mechanisms of resistance. The MICs of GR69153 for 90% of the members of the family Enterobacteriaceae tested were less than 0.5 micrograms/ml, with the exceptions of those for Serratia spp. (4 micrograms/ml), Citrobacter spp. (2 micrograms/ml), and Enterobacter spp. (8 micrograms/ml). Ninety percent of Pseudomonas aeruginosa isolates were susceptible to less than or equal to 1 microgram of GR69153 per ml. With the exception of methicillin-resistant strains, 90% of Staphylococcus aureus isolates were susceptible to less than or equal to 2 micrograms/ml, and GR69153 was four- to eightfold more active than ceftazidime and ceftriaxone against these strains. Isolates of Haemophilus influenzae, Branhamella catarrhalis, Neisseria spp., and Streptococcus pneumoniae (penicillin susceptible) were highly susceptible (MIC for 90% of the strains, less than or equal to 0.12 micrograms/ml). GR69153 was stable to hydrolysis by the TEM-1 and TEM-5, SHV-1 and SHV-2, and K1 beta-lactamases, but some susceptibility to hydrolysis by the TEM-3, TEM-9, and P99 enzymes was observed. The protein-binding activity of GR69153 was 74.5 to 66.8%, depending on the concentration, and serum had little effect upon activity.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashby J., Kirkpatrick B., Piddock L. J., Wise R. The effect of imipenem on strains of Enterobacteriaceae expressing Richmond & Sykes class I beta-lactamases. J Antimicrob Chemother. 1987 Jul;20(1):15–22. doi: 10.1093/jac/20.1.15. [DOI] [PubMed] [Google Scholar]
  2. Curtis N. A., Eisenstadt R. L., East S. J., Cornford R. J., Walker L. A., White A. J. Iron-regulated outer membrane proteins of Escherichia coli K-12 and mechanism of action of catechol-substituted cephalosporins. Antimicrob Agents Chemother. 1988 Dec;32(12):1879–1886. doi: 10.1128/aac.32.12.1879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Kiener P. A., Waley S. G. Reversible inhibitors of penicillinases. Biochem J. 1978 Jan 1;169(1):197–204. doi: 10.1042/bj1690197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  5. Nichols W. W., Hewinson R. G. Rapid and automated measurement of Km and specific Vmax values of beta-lactamases in bacterial extracts. J Antimicrob Chemother. 1987 Mar;19(3):285–295. doi: 10.1093/jac/19.3.285. [DOI] [PubMed] [Google Scholar]
  6. Ohi N., Aoki B., Shinozaki T., Moro K., Noto T., Nehashi T., Okazaki H., Matsunaga I. Semisynthetic beta-lactam antibiotics. I. Synthesis and antibacterial activity of new ureidopenicillin derivatives having catechol moieties. J Antibiot (Tokyo) 1986 Feb;39(2):230–241. doi: 10.7164/antibiotics.39.230. [DOI] [PubMed] [Google Scholar]
  7. POLLOCK M. R. PURIFICATION AND PROPERTIES OF PENICILLINASES FROM TWO STRAINS OF BACILLUS LICHENIFORMIS: A CHEMICAL, PHYSICOCHEMICAL AND PHYSIOLOGICAL COMPARISON. Biochem J. 1965 Mar;94:666–675. doi: 10.1042/bj0940666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Pearson R. D., Steigbigel R. T., Davis H. T., Chapman S. W. Method of reliable determination of minimal lethal antibiotic concentrations. Antimicrob Agents Chemother. 1980 Nov;18(5):699–708. doi: 10.1128/aac.18.5.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Silley P., Griffiths J. W., Monsey D., Harris A. M. Mode of action of GR69153, a novel catechol-substituted cephalosporin, and its interaction with the tonB-dependent iron transport system. Antimicrob Agents Chemother. 1990 Sep;34(9):1806–1808. doi: 10.1128/aac.34.9.1806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Spencer R. C., Wheat P. F., Winstanley T. G., Cox D. M., Plested S. J. Novel beta-lactamase in a clinical isolate of Klebsiella pneumoniae conferring unusual resistance to beta-lactam antibiotics. J Antimicrob Chemother. 1987 Dec;20(6):919–921. doi: 10.1093/jac/20.6.919. [DOI] [PubMed] [Google Scholar]
  11. Watanabe N. A., Nagasu T., Katsu K., Kitoh K. E-0702, a new cephalosporin, is incorporated into Escherichia coli cells via the tonB-dependent iron transport system. Antimicrob Agents Chemother. 1987 Apr;31(4):497–504. doi: 10.1128/aac.31.4.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Yang Y. J., Livermore D. M. Interactions of meropenem with class I chromosomal beta-lactamases. J Antimicrob Chemother. 1989 Sep;24 (Suppl A):207–217. doi: 10.1093/jac/24.suppl_a.207. [DOI] [PubMed] [Google Scholar]

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