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. 1988 Nov;32(11):1666–1675. doi: 10.1128/aac.32.11.1666

In vitro activity of E-1040, a novel cephalosporin with potent activity against Pseudomonas aeruginosa.

H C Neu 1, N X Chin 1, A Novelli 1
PMCID: PMC175949  PMID: 3150915

Abstract

The in vitro activity of E-1040 [(6R,7R)-3-[(4-carbamoyl-1-quinuclidinio)methyl]-7-[2-(5-amino-1,2 ,4- thiadiazol-3-yl)-(Z)-2-methoxyiminoacetoamido]-8-oxo-5-thia- 1- azabicyclo(4,2,0)oct-2-ene-2-carboxylate], a novel cephalosporin, was compared with that of ceftazidime, cefpirome, cefepime, imipenem, and gentamicin. E-1040 inhibited 50% of members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Haemophilus and Neisseria species at less than or equal to 0.25 microgram/ml, and the MIC for 90% of strains tested ranged from 0.06 to 2 micrograms/ml. It was two- to fourfold more active than ceftazidime and similar in activity to cefepime and cefpirome. It inhibited Enterobacter, Citrobacter, Serratia, and Morganella species that were resistant to ceftazidime. E-1040 inhibited imipenem-, piperacillin-, aztreonam-, and tobramycin-resistant P. aeruginosa. It was less active against Xanthomonas maltophilia and P. cepacia but inhibited other Pseudomonas species. The activity of E-1040 against staphylococci and hemolytic streptococci was similar to that of ceftazidime, but E-1040 was less active than cefepime and cefpirome. It did not inhibit Bacteroides spp. There was no inoculum effect or medium effect, and MBCs were within a dilution of MICs. Plasmid beta-lactamases TEM-1, TEM-2, TEM-3 (CTX-1), SHV-1, Staphylococcus aureus, PSE, and CARB did not hydrolyze E-1040. Chromosomal beta-lactamases P99 and K-1 did not hydrolyze E-1040; E-1040 had poor affinity for these enzymes, with a Ki of greater than 100 microM.

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Selected References

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

  1. Fuchs P. C., Jones R. N., Barry A. L., Thornsberry C. Evaluation of the in vitro activity of BMY-28142, a new broad-spectrum cephalosporin. Antimicrob Agents Chemother. 1985 May;27(5):679–682. doi: 10.1128/aac.27.5.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Jones R. N., Thornsberry C., Barry A. L. In vitro evaluation of HR810, a new wide-spectrum aminothiazolyl alpha-methoxyimino cephalosporin. Antimicrob Agents Chemother. 1984 Jun;25(6):710–718. doi: 10.1128/aac.25.6.710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Neu H. C., Chin N. X. A perspective on the present contribution of beta-lactamases to bacterial resistance with particular reference to induction of beta-lactamase and its clinical significance. Chemioterapia. 1985 Feb;4(1):63–70. [PubMed] [Google Scholar]
  4. Neu H. C., Chin N. X., Jules K., Labthavikul P. The activity of BMY 28142 a new broad spectrum beta-lactamase stable cephalosporin. J Antimicrob Chemother. 1986 Apr;17(4):441–452. doi: 10.1093/jac/17.4.441. [DOI] [PubMed] [Google Scholar]
  5. Neu H. C., Chin N. X., Labthavikul P. The in vitro activity and beta-lactamase stability of cefpirome (HR 810), a pyridine cephalosporin agent active against staphylococci, Enterobacteriaceae and Pseudomonas aeruginosa. Infection. 1985 May-Jun;13(3):146–155. doi: 10.1007/BF01642876. [DOI] [PubMed] [Google Scholar]
  6. Neu H. C., Chin N. X. The activity and beta-lactamase stability of cefotetan compared to other beta-lactam antibiotics. Chemioterapia. 1985 Aug;4(4):271–277. [PubMed] [Google Scholar]
  7. Neu H. C. New antibiotics: areas of appropriate use. J Infect Dis. 1987 Mar;155(3):403–417. doi: 10.1093/infdis/155.3.403. [DOI] [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. Richmond M. H., Clark D. C., Wotton S. Indirect method for assessing the penetration of beta-lactamase-nonsusceptible penicillins and cephalosporins in Escherichia coli strains. Antimicrob Agents Chemother. 1976 Aug;10(2):215–218. doi: 10.1128/aac.10.2.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Richmond M. H., Sykes R. B. The beta-lactamases of gram-negative bacteria and their possible physiological role. Adv Microb Physiol. 1973;9:31–88. doi: 10.1016/s0065-2911(08)60376-8. [DOI] [PubMed] [Google Scholar]
  11. Tolxdorff-Neutzling R. M., Wiedemann B. HR 810, a cephalosporin with low affinity for Enterobacter cloacae beta-lactamase. Eur J Clin Microbiol. 1983 Aug;2(4):352–354. doi: 10.1007/BF02019467. [DOI] [PubMed] [Google Scholar]
  12. Zimmermann W. Penetration through the gram-negative cell wall: a co-determinant of the efficacy of beta-lactam antibiotics. Int J Clin Pharmacol Biopharm. 1979 Mar;17(3):131–134. [PubMed] [Google Scholar]

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