Abstract
GV104326 is the first member of a new class of antibiotics (tribactams) selected for development. It combines a particularly broad spectrum (including gram-negative and gram-positive aerobes and anaerobes) with high potency, resistance to beta-lactamases, and complete stability to dehydropeptidases. Comparative MICs were determined for GV104326 against 415 recent clinical isolates (including beta-lactamase producers), using representative antibacterial agents (imipenem, amoxicillin-clavulanic acid, cefpirome, ciprofloxacin, gentamicin, and erythromycin). GV104326 was particularly active against gram-positive bacteria; in general, its in vitro activity was equivalent to that of imipenem, equivalent to or better than that of amoxicillin-clavulanic acid, and superior to that of cefpirome, ciprofloxacin, and erythromycin. Against gram-negative bacteria, GV104326 possessed activity similar to that of imipenem and cefpirome against enterobacteria and Haemophilus spp. but its activity was superior to that of amoxicillin-clavulanic acid. GV104326 showed excellent antianaerobe activity. GV104326 was stable to all clinically relevant beta-lactamases and was rapidly lethal to susceptible bacteria. In Escherichia coli, GV104326 bound predominantly to PBPs 1a and 2 and at low concentrations osmotically stable round forms were observed. GV104326 showed an affinity for PBPs 2 and 4 of Staphylococcus aureus.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bush K. Beta-lactamase inhibitors from laboratory to clinic. Clin Microbiol Rev. 1988 Jan;1(1):109–123. doi: 10.1128/cmr.1.1.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bush K. Characterization of beta-lactamases. Antimicrob Agents Chemother. 1989 Mar;33(3):259–263. doi: 10.1128/aac.33.3.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bush K., Singer S. B. Biochemical characteristics of extended broad spectrum beta-lactamases. Infection. 1989 Nov-Dec;17(6):429–433. doi: 10.1007/BF01645566. [DOI] [PubMed] [Google Scholar]
- Gutmann L., Kitzis M. D., Acar J. F. Evolution of enzymatic mechanisms of resistance among beta-lactam antibiotics. J Int Med Res. 1990;18 (Suppl 4):37D–47D. [PubMed] [Google Scholar]
- Jones R. N. The current and future impact of antimicrobial resistance among nosocomial bacterial pathogens. Diagn Microbiol Infect Dis. 1992 Feb;15(2 Suppl):3S–10S. [PubMed] [Google Scholar]
- Kahan F. M., Kropp H., Sundelof J. G., Birnbaum J. Thienamycin: development of imipenen-cilastatin. J Antimicrob Chemother. 1983 Dec;12 (Suppl 500):1–35. doi: 10.1093/jac/12.suppl_d.1. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Neu H. C. The crisis in antibiotic resistance. Science. 1992 Aug 21;257(5073):1064–1073. doi: 10.1126/science.257.5073.1064. [DOI] [PubMed] [Google Scholar]
- Philippon A., Labia R., Jacoby G. Extended-spectrum beta-lactamases. Antimicrob Agents Chemother. 1989 Aug;33(8):1131–1136. doi: 10.1128/aac.33.8.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanders C. C. beta-Lactamases of gram-negative bacteria: new challenges for new drugs. Clin Infect Dis. 1992 May;14(5):1089–1099. doi: 10.1093/clinids/14.5.1089. [DOI] [PubMed] [Google Scholar]
- Spratt B. G. Properties of the penicillin-binding proteins of Escherichia coli K12,. Eur J Biochem. 1977 Jan;72(2):341–352. doi: 10.1111/j.1432-1033.1977.tb11258.x. [DOI] [PubMed] [Google Scholar]