Abstract
BRL 17421 is a new semisynthetic beta-lactam antibiotic with an unusual spectrum of antibacterial activity. The compound exhibits exceptional stability to a wide range of bacterial beta-lactamases and is active against the majority of Enterobacteriaceae, including strains highly resistant to many of the penicillins and cephalosporins currently available. Among the clinical isolates of Enterobacteriaceae tested, the frequency of strains resistant to BRL 17421 was found to be low, and there was a slow rate of emergence of resistance during in vitro studies. BRL 17421 was highly active against Haemophilus influenzae and Neisseria gonorrhoeae, including beta-lactamase-producing strains. The compound was markedly less active against Pseudomonas aeruginosa and Bacteroides fragilis than against the Enterobacteriaceae. Against the gram-positive bacteria, BRL 17421 showed a very low level of activity. BRL 17421 was found to be 85% bound to human serum, and the antibacterial activity was diminished two- to fourfold in the presence of human serum. Against experimental infections in mice, the activity of BRL 17421 reflected the properties observed in vitro. Studies in human volunteers showed unusually high and prolonged serum concentrations of the compound after parenteral dosage, with a serum half-life of about 5 h, and approximately 85% of the dose was recovered unchanged in the urine. BRL 17421 was poorly absorbed after oral administration. The compound was well tolerated after intramuscular and intravenous administration in volunteers, with no adverse side effects.
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- Barza M., Tally F. P., Jacobus N. V., Gorbach S. L. In vitro activity of LY127935. Antimicrob Agents Chemother. 1979 Sep;16(3):287–292. doi: 10.1128/aac.16.3.287. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matthew M. Plasmid-mediated beta-lactamases of Gram-negative bacteria: properties and distribution. J Antimicrob Chemother. 1979 Jul;5(4):349–358. doi: 10.1093/jac/5.4.349. [DOI] [PubMed] [Google Scholar]
- Nayler J. H. Advances in penicillin research. Adv Drug Res. 1973;7:1–105. [PubMed] [Google Scholar]
- Neu H. C., Fu K. P., Aswapokee N., Aswapokee P., Kung K. Comparative activity and beta-lactamase stability of cefoperazone, a piperazine cephalosporin. Antimicrob Agents Chemother. 1979 Aug;16(2):150–157. doi: 10.1128/aac.16.2.150. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Callaghan C. H., Acred P., Harper P. B., Ryan D. M., Kirby S. M., Harding S. M. GR 20263, a new broad-spectrum cephalosporin with anti-pseudomonal activity. Antimicrob Agents Chemother. 1980 May;17(5):876–883. doi: 10.1128/aac.17.5.876. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Callaghan C. H. Description and classification of the newer cephalosporins and their relationships with the established compounds. J Antimicrob Chemother. 1979 Nov;5(6):635–671. doi: 10.1093/jac/5.6.635. [DOI] [PubMed] [Google Scholar]
- Peterson L. R., Gerding D. N. Influence of protein binding of antibiotics on serum pharmacokinetics and extravascular penetration: clinically useful concepts. Rev Infect Dis. 1980 May-Jun;2(3):340–348. doi: 10.1093/clinids/2.3.340. [DOI] [PubMed] [Google Scholar]
- 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]
- Shannon K., King A., Warren C., Phillips I. In vitro antibacterial activity and susceptibility of the cephalosporin Ro 13-9904 to beta-lactamases. Antimicrob Agents Chemother. 1980 Aug;18(2):292–298. doi: 10.1128/aac.18.2.292. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sykes R. B., Matthew M. The beta-lactamases of gram-negative bacteria and their role in resistance to beta-lactam antibiotics. J Antimicrob Chemother. 1976 Jun;2(2):115–157. doi: 10.1093/jac/2.2.115. [DOI] [PubMed] [Google Scholar]