Evaluation of novel antipseudomonal drugs using the serum bactericidal activity test

Serum bactericidal activity against Pseudomonas aeruginosa was determined in six volunteers 1 and 4 h after administration of 2 g ceftazidime, 4 g piperacillin, 500 mg imipenem, 80 mg tobramycin and four combinations of these agents. Ceftazidime produced the highest serum bactericidal titers, killing 100% and 86% of the 50 Pseudomonas aeruginosa strains tested after 1 and 4 h respectively at a serum dilution of 1:8. Imipenem had lower serum bactericidal titers than ceftazidime, killing 88% of the isolates after 1 h at a serum dilution of 1:8. The combination showed only slightly higher titers. Killing curves were determined for nine strains of Pseudomonas aeruginosa using undiluted volunteer serum drawn 1 h after administration of the antibiotics. The combinations ceftazidime/tobramycin and piperacillin/tobramycin exhibited higher killing activity than the single drugs. As the activity of the aminoglycosides could be underestimated on the basis of their low serum bactericidal titers, it is concluded that determination of these titers is inappropriate for evaluating the efficacy of the aminoglycosides.