Comparative serum bactericidal activity against Pseudomonas aeruginosa of six antipseudomonal agents

Serum levels and serum bactericidal activities of six antipseudomonal agents were studied comparatively in 60 patients. Single intravenous doses of gentamicin (1.5 mg/kg), piperacillin (4 g), ceftazidime (1 g), imipenem (0.5 g), aztreonam (1 g), and ciprofloxacin (200 mg) were given over 30 min to 10 patients each, and serum samples were obtained 30 min, 1, 2, 3, 4, 6, 8 and 12 h after beginning the infusion. Serum bactericidal activity was determined by the broth microdilution method against 10 recent isolates of Pseudomonas aeruginosa. Mean peak serum levels were as follows: gentamicin 10.4 micrograms/ml, piperacillin 227.5 micrograms/ml, ceftazidime 43.5 micrograms/ml, imipenem 17.3 micrograms/ml, aztreonam 42.3 micrograms/ml, and ciprofloxacin 3.9 micrograms/ml. All agents demonstrated effective serum bactericidal activity (geometric mean titer > 1:2) at peak serum levels. Ceftazidime was by far the most potent compound with a mean titer of 1:46.5, followed by ciprofloxacin (1:17), imipenem (1:13.7), and aztreonam (1:13.4). Ceftazidime also showed the longest duration of activity with a mean titer of 1:5.1 at 4 h. Based on our results, ceftazidime appeared to be the most potent antipseudomonal agent, while gentamicin and piperacillin were the least effective.