Comparison of the Pharmacokinetic and Pharmacodynamic Activity of Piperacillin and Mezlocillin

Abstract

Study Objective. To compare serum bactericidal activity over time and pharmacokinetics resulting from single doses of piperacillin (PIP) and a single dose of mezlocillin (MEZ).Design. Open‐label, randomized, three‐way crossover study.Setting. Hartford Hospital Clinical Research Center.Patients. Nine healthy volunteers.Interventions. Subjects received single doses of PIP 3 and 4 g/70 kg, and a single dose of MEZ 5 g/70 kg.Measurements and Main Results. Test organisms were two clinical isolates of Pseudomonas aeruginosa. Pharmacodynamic analysis revealed that PIP 4 g had 2‐ to 3‐fold higher peak serum bactericidal activity at the end of infusion and 4‐ to 5‐fold higher activity at 0.5 hour than did MEZ 5 g, and also provided approximately 1 hour additional activity over MEZ 5 g. Pharmacokinetic analysis revealed that serum concentrations resulting from PIP 4 g remained above the minimum inhibitory concentration of our test strains almost twice as long as MEZ 5 g.Conclusion. Since mezlocillin 5 g every 8 hours is currently proving to be effective at many institutions, and since piperacillin 4 g demonstrates superior pharmacokinetic and pharmacodynamic activity, we believe that piperacillin 4 g every 8 hours could be used instead, with resulting cost savings.