Abstract
Studies were performed to determine the effects of BRL 42715, a potent beta-lactamase inhibitor, on the activity of cefazolin and piperacillin against experimental intraperitoneal infections caused by either Escherichia coli or Serratia marcescens in rats. Compounds were administered to rats as a continuous infusion of an exponentially diluted solution to simulate in rat plasma the concentration-versus-time curves obtained for humans following intravenous bolus administration. A simulated 1-g dose of cefazolin was ineffective in reducing the bacterial counts in blood and peritoneal fluid samples of animals infected with S. marcescens US20, which produced class Ia beta-lactamase, and as a result, mortality was similar to that of infected controls. Similarly, a simulated 2-g dose of piperacillin was ineffective in reducing bacterial numbers and mortality in animals infected with E. coli 41548, producing a TEM-1 beta-lactamase. However, when the antibiotics were coadministered with BRL 42715, bacterial numbers were reduced significantly and all animals survived at least 16 h after infection. These data demonstrate the ability of BRL 42715 to potentiate the activity of cefazolin and piperacillin against beta-lactamase-producing bacteria that would otherwise be resistant to these antibiotics and illustrate the application of a model to simulate human serum concentrations in conscious rats.
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Selected References
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- Bergan T. Comparative pharmacokinetics of cefazolin, cephalothin, cephacetril, and cephapirine after intravenous administration. Chemotherapy. 1977;23(6):389–404. doi: 10.1159/000222009. [DOI] [PubMed] [Google Scholar]
- Coleman K., Griffin D. R., Page J. W., Upshon P. A. In vitro evaluation of BRL 42715, a novel beta-lactamase inhibitor. Antimicrob Agents Chemother. 1989 Sep;33(9):1580–1587. doi: 10.1128/aac.33.9.1580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Comber K. R., Osborne C. D., Sutherland R. Comparative effects of amoxycillin and ampicillin in the treatment of experimental mouse infections. Antimicrob Agents Chemother. 1975 Feb;7(2):179–185. doi: 10.1128/aac.7.2.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerber A. U., Brugger H. P., Feller C., Stritzko T., Stalder B. Antibiotic therapy of infections due to Pseudomonas aeruginosa in normal and granulocytopenic mice: comparison of murine and human pharmacokinetics. J Infect Dis. 1986 Jan;153(1):90–97. doi: 10.1093/infdis/153.1.90. [DOI] [PubMed] [Google Scholar]
- Gerber A. U. Impact of the antibiotic dosage schedule on efficacy in experimental soft tissue infections. Scand J Infect Dis Suppl. 1990;74:147–154. [PubMed] [Google Scholar]
- Nielsen-Kudsk F. Pharmacokinetic analysis and calculations using a program for the minicalculator TI-59. Int J Biomed Comput. 1981 Jan;12(1):83–96. doi: 10.1016/0020-7101(81)90028-3. [DOI] [PubMed] [Google Scholar]
- Roosendaal R., Bakker-Woudenberg I. A. Impact of the antibiotic dosage schedule on efficacy in experimental lung infections. Scand J Infect Dis Suppl. 1990;74:155–162. [PubMed] [Google Scholar]
- Tjandramaga T. B., Mullie A., Verbesselt R., De Schepper P. J., Verbist L. Piperacillin: human pharmacokinetics after intravenous and intramuscular administration. Antimicrob Agents Chemother. 1978 Dec;14(6):829–837. doi: 10.1128/aac.14.6.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Woodnutt G., Catherall E. J., Kernutt I., Mizen L. Temocillin efficacy in experimental Klebsiella pneumoniae meningitis after infusion into rabbit plasma to simulate antibiotic concentrations in human serum. Antimicrob Agents Chemother. 1988 Nov;32(11):1705–1709. doi: 10.1128/aac.32.11.1705. [DOI] [PMC free article] [PubMed] [Google Scholar]