BRL-36650: in vitro studies and assessment of serum bactericidal activity after single-dose administration in volunteers.

Ten healthy volunteers received 1 g of BRL-36650, a new formamido-penicillin derivative, given by intravenous infusion over 15 min. Levels in serum were measured microbiologically 30, 60, and 120 min after the start of the 15-min infusion and were (mean +/- standard deviation) 102.7 +/- 28.4, 59.7 +/- 11.5, and 9.6 +/- 1.9 mg/liter, respectively. A total of 10 strains each of Escherichia coli, Klebsiella pneumoniae, Serratia spp., and Enterobacter spp. and 14 strains of Pseudomonas aeruginosa were selected according to their susceptibility or resistance to piperacillin for the study of serum bactericidal activity (SBA). The MICs and MBCs of these strains were influenced by the choice of medium. Median SBA against E. coli and K. pneumoniae were greater than or equal to 1:2,048 and 1:512, respectively. The SBA against piperacillin-susceptible Serratia spp. (1:256), Enterobacter spp. (1:128), and P. aeruginosa (1:32) were significantly higher than against piperacillin-resistant strains (1:32, 1:8, and 1:4, respectively). Killing curves confirmed the high bactericidal activities obtained against the majority of strains. In the case of one Enterobacter sp. and one P. aeruginosa isolate with an MBC greater than or equal to 32, the absence of killing was noted.