Influence of human albumin on bactericidal or antibacterial activities of cephems and monobactams

Influence of human albumin on bactericidal or antibacterial activities of 11 beta-lactams were examined. The 11 beta-lactams included second generation cephems (cefsulodin, cefotiam and cefmetazole), third generation cephems (ceftazidime, latamoxef, cefmenoxime, cefoperazone, cefotetan and cefpiramide) and monobactams (carumonam and aztreonam). The micro-broth-dilution method was used to determine antibacterial activities. Bactericidal activities were determined using the time-kill method. Used in the broth-dilution method were 2 media, MUELLER-HINTON broth (MHB) and the same medium supplemented with 5 g human albumin/d1 (MHB-A). The first experiment was to compare minimum inhibitory concentrations (MICs) determined in MHB were compared with those in MHB-A of 6 antibiotics against Staphylococcus aureus FDA 209P JC-1, of 7 antibiotics against Escherichia coli ATCC 25922 and of 5 antibiotics against Pseudomonas aeruginosa NCTC 10490. MICs using MHB-A were higher than MIC using MHB for 2 of the 6 antibiotics against S. aureus, and for all the 7 antibiotics against E. coli, and for 3 of the 5 antibiotics against P. aeruginosa. The second experiment was done to compare MICs of 5 antibiotics determined in MHB-A with those determined in MHB against 10 clinical isolates of S. aureus, of 6 antibiotics against 10 clinical isolates of Klebsiella pneumoniae and of 6 antibiotics against 10 clinical isolates of P. aeruginosa. The results obtained in the second experiment were varied for different antibiotics and different strains of organisms, and same antibiotics produced different results for different strains. MICs determined in MHB-A were lower than those in MHB for antibiotics with relatively low protein binding rates against 22 of 170 isolates tested (12.9%), whereas the former was higher than the latter against 103 out of 170 isolates tested (60.6%). MICs of antibiotics with relatively high protein binding rates showed an opposite trend. In the third experiment, time-kill curves were determined in the 2 media for 5 antibiotics against S. aureus FDA 209P JC-1, for 6 drugs against E. coli ATCC 25922 and for 5 drugs against P. aeruginosa NCTC 10490. The concentrations of these antibiotics used were 1/2 x MIC, 1 x MIC and 2 x MIC. MICs determined in the first experiment were used here. Time-kill curves determined in MHB-A didn't reflect MICs determined in MHB. Using MHB-A, antibiotics with lower MICs determined in MHB-A showed bactericidal activities in lower concentrations. Human albumin influenced antibacterial or bactericidal activities of beta-lactams.(ABSTRACT TRUNCATED AT 400 WORDS)