Serum bactericidal activity of cefoperazone and ceftazidime at increasing dosages against Pseudomonas aeruginosa

Abstract

Serum bactericidal activity (SBA) greater than or equal to 1:8 correlates with the clinical effectiveness of antibiotics. Ten healthy young volunteers received iv on separate days cefoperazone 1, 2, or 3 g and ceftazidime 1, 2, or 3 g. The serum levels 1 and 6 h after the administration of cefoperazone 1, 2 and 3 g were respectively 52 and 7 mg/l, 122 and 13 mg/l, 190 and 22 mg/l. The serum levels of ceftazidime 1, 2 and 3 g, after 1 h and 6 h were 28 and 8, 56 and 9, 78 and 13 mg/l. The SBA was determined against seven strains of Pseudomonas aeruginosa with MBC of 1.6-12.5 mg/l of cefoperazone and 0.8-6.2 mg/l of ceftazidime. Increased dosage of cefoperazone and ceftazidime led to a significant increase in the SBA's greater than or equal to 1:8 at 1 h (P less than 0.01). In sera obtained 1 h and 6 h after the injection of the antibiotics, 97% and 51% of the strains were inhibited by ceftazidime 2 g, while 1 g was inhibitory on 84% (1 h) and 8% (6 h) of the strains. Ceftazidime 1 g produced SBA's greater than or equal to 1:8 significantly more often than did cefoperazone 3 g (P less than 0.01) at 1 h. The rate of killing with all ceftazidime regimens was similar and slightly higher than that of any cefoperazone regimen. Ceftazidime seems more effective than cefoperazone against Ps. aeruginosa; however, increased MBC values were observed during killing curves studies with both drugs.